bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast carcinoma diagnosis, treatment, and prognosis before and after the introduction of mass mammographic screening
Authors: Ernst Miranda F. , Voogd Adri C. , Coebergh Jan Willem W. , Roukema Jan A. 
Published: March 2004

AbstractBACKGROUNDThe introduction of breast carcinoma screening leads to early detection and is believed to reduce mortality and increase the proportion of patients for whom breast‐conserving surgery is possible.METHODSIn 1992, a population‐based mammographic screening program was introduced in the Dutch city of Tilburg and its surroundings; the program achieved total coverage in 1996. The authors examined the effects of this screening program by investigating disease stage, treatment, and survival among women diagnosed with breast carcinoma at a teaching hospital in Tilburg during the periods 1985–1991 and 1992–1999.RESULTSBetween January 1, 1985, and December 31, 1999, 1400 patients were diagnosed with breast carcinoma. Among patients ages 50–69 years, the proportion of TNM Stage I breast carcinoma increased from 24% in 1985–1991 to 45% in 1992–1999 (P < 0.001). The proportion of patients age < 50 years with invasive breast carcinoma who underwent breast‐conserving surgery decreased from 45% to 33% (P = 0.011). Among patients ages 50–69 years, the overall survival rate during the period from 1992 to 1999 was significantly greater than the corresponding rate during the period from 1985 to 1991 (P = 0.0009). Even after adjustments were made for tumor stage and patient age, a slight reduction in mortality risk was observed in this age group. No difference in stage distribution or prognosis was found among patients age < 50 years or among patients age ≥ 70 years. Of the 168 invasive malignancies found in patients ages 50–69 years between 1997 and 1999, 68 (40%) were detected by the screening program, 47 (28%) were interval malignancies, and 53 (32%) were detected in nonparticipants or in women who did not participate in 1 or more screening rounds. Patients with screen‐detected tumors had a much more favorable prognosis than did patients with interval malignancies (P = 0.0018) or patients with clinically detected breast carcinoma (P < 0.0001).CONCLUSIONSBetween 1992 and 1999, after the introduction of breast carcinoma screening, improved prognosis and more favorable tumor stage were observed among patients ages 50–69 years. Even after the screening program was fully implemented in 1996, the majority of invasive malignancies still were detected between screening rounds or in patients who did not participate in the program. Cancer 2004;100:1337–44. © 2004 American Cancer Society.
Hypermethylation ofFHITas a prognostic marker in nonsmall cell lung carcinoma
Authors: Maruyama Riichiroh , Sugio Kenji , Yoshino Ichiro , Maehara Yoshihiko , Gazdar Adi F. 
Published: March 2004

AbstractBACKGROUNDMethylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC).METHODSThe methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation‐specific polymerase chain reaction.RESULTSThe methylation frequencies of the genes tested in NSCLC specimens were 52% for E‐cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RARβ) and H‐cadherin (CDH13), 20% forp16INK4A, 0.8% for O6‐methylguanine‐DNA‐methyltransferase (MGMT), and 0% for glutathione S‐transferase P1 (GSTP1). The survival of the patients withFHITmethylation‐positive tumors was found to be significantly shorter than that for those patients with methylation‐negative tumors (P= 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P= 0.007). In contrast, there were no significant survival differences noted between the methylation‐positive and methylation‐negative tumors for the other genes tested. In addition, based on multivariate analyses,FHITmethylation‐positive status was found to be independently associated with poor survival (P= 0.046) and disease stage (P< 0.0001).CONCLUSIONSThe results of the current study suggest that methylation ofFHITis a useful biomarker of biologically aggressive disease in patients with NSCLC. Cancer 2004;100:1472–7. © 2004 American Cancer Society.
MOCVD of LaMnO3 on Biaxially Textured Ni‐based Substrates in a Reducing Atmosphere
Authors: Gorbenko O.Y. , Stadel O. , Wahl G. , Kaul A.R. 
Published: March 2004

AbstractThe metal–organic (MO) CVD process was modified to allow the in‐situ deposition of perovskite manganites on biaxially textured Ni‐based metal tapes (RABiTS). The modification consists of the creation of the protective atmosphere by simultaneous introduction of ammonia and water. Such an atmosphere prevents the oxidation of Ni and the reduction of manganites into non‐perovskite phases. MOCVD experiments were accomplished in the band‐type reactor using the band evaporation system at 800 °C and 850 °C. Orthorhombic LaMnO3 film demonstrates (101) orientation (i.e. (001) orientation in cubic perovskite notation) minimizing lattice mismatch with the nickel substrate. The film stoichiometry, total pressure, water and ammonia flows greatly influence the quality of the film orientation. The oriented perovskite manganite films on Ni tapes can be used as buffers for high Tc superconductors for high current applications as well as magnetoresistance‐based sensors of the magnetic field.
Controlling Surface Composition and Zeta Potential of Chemical Vapor Synthesized Alumina‐Silica Nanoparticles
Authors: Sieger H. , Winterer M. , Mühlenweg H. , Michael G. , Hahn H. 
Published: March 2004

AbstractUltrafine alumina–silica powders with varying composition gradients within the particles have been produced by chemical vapor synthesis in a hot‐wall reactor using the precursors tetraethoxysilane (TEOS) and aluminiumtrisecbutylate (ASB). The surface chemistry at the particle/liquid interface in aqueous dispersions can be adjusted by varying the process parameters. The powders have been characterized by nitrogen adsorption, X‐ray diffraction (XRD), transmission electron microscopy (TEM) with local energy dispersive X‐ray (EDX) analysis, X‐ray fluorescence (XRF) analysis, and electrophoretic mobility measurements.
Growth of Praseodymium Oxide and Praseodymium Silicate Thin Films by Liquid Injection MOCVD
Authors: Aspinall H.C. , Gaskell J. , Williams P.A. , Jones A.C. , Chalker P.R. , Marshall P.A. , Smith L.M. , Critchlow G.W. 
Published: March 2004

AbstractThin films of praseodymium oxide have been deposited by liquid injection MOCVD using the volatile praseodymium alkoxide, [Pr(mmp)3] (mmp = 1‐methoxy‐2‐methyl‐2‐propanolate, OCMe2CH2OMe). The films were grown over a wide range of substrate temperatures (250–600 °C) and were found to consist predominantly of the Pr6O11 phase. Praseodymium silicate films containing ∼ 16–22 at.‐% Si were deposited over the temperature range 350–550 °C using [Pr{N(SiMe3)2}3] in the absence of any additional Si source.
Up‐regulation of muscle‐specific transcription factors during embryonic somitogenesis of zebrafish (Danio rerio) by knock‐down of myostatin‐1
Authors: Amali Aseervatham Anusha , Lin Cliff Ji‐Fan , Chen Yi‐Hsuan , Wang Wei‐Lun , Gong Hong‐Yi , Lee Chiou‐Yueh , Ko Yen‐Lin , Lu Jenn‐Khan , Her Guor Mour , Chen Thomas T. , Wu Jen‐Leih 
Published: March 2004

AbstractMyostatin, a secreted growth and differentiation factor (GDF‐8) belongs to transforming growth factor (TGF‐β) superfamily that plays as a negative regulator of skeletal muscle development and growth. Recently, myostatin has been isolated from fish; however, its role in muscle development and growth remains unknown. Here, we present the expression of myostatin during development and the effects of its knock‐down on various genes such as muscle regulatory transcription factors (MRFs), muscle‐specific proteins (MSP), and insulin‐like growth factors (IGFs). The myostatin expression was found to be maternal as it starts in one‐cell stage onward. The reverse transcription‐polymerase chain reaction (RT‐PCR), in situ hybridization, and Southern and Northern blots demonstrated that the myostatin expression is not only restricted to skeletal muscle, but it expressed all the tested tissues. Expression of myostatin was effected by using antisense morpholinos resulted in significant phenotypic difference in stages 18 and 20 hours postfertilization (hpf). To confirm the specificity of myostatin morpholino, furthermore, a rescue experiment was conducted. The length as well as width of somites was increased with almost no gap in between the somites. In addition, it deserves to mention that this is a first animal model that shows changes in the size of the somites. Moreover, analyses of MRFs, MSP, and IGFs in the knock‐down embryos by RT‐PCR revealed the up‐regulation of MyoD, Myogenin, and Mck transcription, whereas IGF‐2 transcription showed mild response with no effect on IGF‐1, Desmin, and Myf5. In situ hybridization showed that there was an increase in the number of somites from 3 to 4 at 13 and 22 hpf. Taken together, these data suggest that myostatin plays a major role during myogenesis, apart from inhibition of proliferation as well as differentiation. Developmental Dynamics 229:847‐856, 2004. © 2004 Wiley‐Liss, Inc.
Reciprocal chemokine receptor and ligand expression in the human placenta: Implications for cytotrophoblast differentiation
Authors: Drake Penelope M. , Red‐Horse Kristy , Fisher Susan J. 
Published: March 2004

AbstractAt the onset of pregnancy, the human placenta, which forms the interface between the embryo/fetus and the mother, must rapidly develop into a life‐sustaining organ. The many unusual processes entailed in placental development include the poorly understood phenomenon of maternal tolerance of the hemiallogeneic cells of the conceptus, including, most remarkably, placental trophoblasts that invade the uterine wall. To investigate whether this fetal organ exerts control over the maternal immune system at the level of leukocyte trafficking, we examined placental expression of chemokines, well‐known cytokine regulators of leukocyte movements. In situ hybridization revealed abundant expression of 13 chemokines in the stromal but not the trophoblast compartment of chorionic villi. Potential roles for these molecules include recruitment of the resident macrophage (Hofbauer cell) population to the villi. In parallel, cytotrophoblast production of a panel of nine chemokine receptors was assessed by using RNase protection assays. The numerous receptors detected suggested the novel possibility that the paracrine actions of chemokine ligands derived from either the villous stroma or the decidua could mediate general aspects of placental development, with specific contributions to cytotrophoblast differentiation along the pathway that leads to uterine invasion. Developmental Dynamics 229:877–885, 2004. © 2004 Wiley‐Liss, Inc.
Myofibrillogenesis in the developing chicken heart: Role of actin isoforms and of the pointed end actin capping protein tropomodulin during thin filament assembly
Authors: Ehler Elisabeth , Fowler Velia M. , Perriard Jean‐Claude 
Published: March 2004

AbstractRecently, important differences between myofibrillogenesis in cultured cardiomyocytes vs. the three‐dimensional setting in situ could be determined. We investigated thin filament assembly in situ by confocal microscopy of whole‐mount preparations of immunostained embryonic chicken hearts. Of interest, a distinct localisation of different actin isoforms was observed in immature thin filaments. Cardiac α‐actin is restricted to filaments with a length comparable to mature thin filaments as soon as the first contractions occur, while vascular α‐actin makes up filaments that extend toward the M‐band. The pointed‐end actin filament capping protein tropomodulin can be found initially in close association with the plasma membrane, but attains its mature localisation pattern at the ends of the thin filaments only comparatively late during myofibrillogenesis. Thus tropomodulin acts as a length stabilising element of actin filaments also in developing cardiomyocytes in situ, but plays an additional role together with membrane‐associated actin filaments in the earliest steps of myofibril assembly. Developmental Dynamics 229:745–755, 2004. © 2004 Wiley‐Liss, Inc.
Protein phosphatase 1α is required for murine lung growth and morphogenesis
Authors: Hormi‐Carver Kadija‐Kathy , Shi Wei , Liu Cathy W.Y. , Berndt Norbert 
Published: March 2004

AbstractProtein phosphatase 1 (PP1) plays important roles in cell cycle control and apoptosis, two processes that impinge on morphogenesis and differentiation. Following the precedent set by other molecules regulating the cell cycle and apoptosis, we hypothesized that PP1 may have context‐specific roles in development. Therefore, we have studied the spatial and temporal expression of PP1α during murine lung development and determined the consequences of loss of PP1α function on branching morphogenesis. By using an immunohistochemical approach, we show here that PP1α was expressed throughout the epithelium and mesenchyme upon the emergence of the lung primordium on embryonic day 10, with immunostaining exclusively extranuclear. During the late pseudoglandular stage, PP1α was predominantly expressed in the distal lung epithelium, whereas the mesenchyme contained very little or no PP1α protein. Peri‐ and postnatally, PP1α immunostaining was mostly nuclear in apparently differentiated cells, as judged by colocalization with well‐known markers for lung differentiation. Exposure of fetal lung explants to antisense oligodeoxynucleotides against PP1α, resulted in decreased overall size of the cultured lung, a defect in forming new airways, lack of expression of surfactant protein C, and histologic signs of poor differentiation. These data suggest that PP1α is required for branching morphogenesis and differentiation. Developmental Dynamics 229:791–801, 2004. © 2004 Wiley‐Liss, Inc.
nlz Gene family is required for hindbrain patterning in the zebrafish
Authors: Hoyle Jacqueline , Tang Yixin P. , Wiellette Elizabeth L. , Wardle Fiona C. , Sive Hazel 
Published: March 2004

AbstractThis study describes the conserved nlz gene family whose members encode unusual zinc finger proteins. In the zebrafish neurectoderm, both nlz1 and the newly isolated nlz2 are expressed in the presumptive hindbrain and midbrain/hindbrain boundary, where expression of nlz1 is dependent on pax2a. In addition, nlz2 is uniquely expressed more anteriorly, in the presumptive midbrain and diencephalon. Overexpression of Nlz proteins during gastrula stages inhibits hindbrain development. In particular, ectopically expressed Nlz1 inhibits formation of future rhombomeres 2 and 3 (r2, r3), whereas neighboring r1 and r4 are not affected. Conversely, simultaneous reduction of Nlz1 and Nlz2 protein function by expression of antisense morpholino‐modified oligomers leads to expansion of future r3 and r5, with associated loss of r4. These data indicate that one function of the nlz gene family is to specify or maintain r4 identity, and to limit r3 and r5 during hindbrain formation. Developmental Dynamics 229:835–846, 2004. © 2004 Wiley‐Liss, Inc.
Knock‐in of nuclear localised β‐galactosidase reveals that the tyrosine phosphatase Ptprv is specifically expressed in cells of the bone collar
Authors: Dacquin R. , Mee P.J. , Kawaguchi J. , Olmsted‐Davis E.A. , Gallagher J.A. , Nichols J. , Lee K. , Karsenty G. , Smith A. 
Published: March 2004

AbstractPtprv is a member of the transmembrane tyrosine phosphatase gene family reported to be expressed in osteoblasts and gonads. To better define the developmental and tissue specificity of Ptprv expression, we generated knock‐in mice expressing a nuclear localised β‐galactosidase reporter under the control of resident Ptprv regulatory elements. Histochemical staining of Ptprv‐nLacZ mice revealed that Ptprv expression is readily detectable in the foetal gonadal ridge of both sexes and in adult gonads where it is localised to Sertoli cells of the testis and celomic epithelial cells of the ovaries. During early limb development, Ptprv expression is prominent in the apical ectodermal ridge of the limb bud. At latter stages of development, Ptprv is predominantly expressed in the perichondrial and periosteal region of long bones, known as the bone collar. In contrast to previous indications from in vitro studies, there is little if any expression in mature osteoblasts in vivo. Analysis of Ptprv mRNA localisation by in situ hybridization in parallel with molecular markers of chondrocytes and osteoblasts confirmed the specific expression of Ptprv in immature bone collar cells. The specificity of Ptprv expression in these cells may be a useful tool to elucidate their role in the transition of skeletal elements from cartilage template to bone. Developmental Dynamics 229:826–834, 2004. © 2004 Wiley‐Liss, Inc.
The tyrosine kinase Syk is required for light chain isotype exclusion but dispensable for the negative selection of B cells
Authors: Meade Josephine , Tybulewicz Victor L. J. , Turner Martin 
Published: March 2004

AbstractIn this study we set out to test whether Syk was required for negative selection of immature B cells. B cells expressing a B cell antigen receptor (BCR) transgene (3–83, anti‐H‐2Kk) underwent negative selection independently of Syk in both fetal liver organ culture and radiation chimera models. Furthermore, Syk‐independent negative selection was not reversed by transgenic overexpression of Bcl‐2. Receptor editing was not apparent in Syk‐deficient B cells, presumably as a consequence of the failure of mature edited B cells to develop in the absence of Syk. Interestingly, light chain isotype exclusion by the BCR transgene failed in the absence of Syk. We observed a dramatic reduction in the overall BCR‐mediated tyrosine phosphorylation of cellular proteins in Syk‐deficient immature B cells. However, the tyrosine phosphorylation of a number of substrates including phospholipase Cγ2, although reduced, was not completely abrogated. BCR ligation triggered an increase in calcium flux in the absence of Syk. Thus signaling events that mediate negative selection can still occur in the absence of Syk. This may be due to redundancy with zeta‐associated protein 70 (ZAP‐70), which we demonstrate to be expressed in immature B cells.
Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin
Authors: Han Xiaobing , Fan Yijun , Wang Shuhe , Yang Jie , Bilenki Laura , Qiu Hongyu , Jiao Lei , Yang Xi 
Published: March 2004

AbstractOur previous study has shown that Chlamydia lung infection can inhibit local eosinophilic inflammation induced by allergen sensitization and challenge, which is correlated with altered cytokine production. In the present study, we examined the role played by dendritic cells (DC) in chlamydial infection‐mediated modulation of allergic responses. The results showed that DC freshlyisolated from Chlamydia‐infected mice (iIDC), unlike those from naive control mice (iNDC), could efficiently modulate immune responses to ovalbumin in vitro and in vivo. Co‐culture of freshly isolated DC with naive CD4 cells from T cell receptor transgenic mice (DO11.10) showed that iIDC directed Th1‐dominant, while iNDC directed Th2‐dominant, allergen‐specific CD4 T cell responses. Moreover, adoptive transfer of iIDC, but not iNDC, could inhibit systemic and local eosinophilia induced by allergen exposure. The reduction of eosinophilia was associated with a decrease in IL‐5 receptor expression on bone marrow cells and the production of IL‐5 and IL‐13 by T lymphocytes. Analysis of the DC showed that iIDC expressed significantly higher levels of mRNA for Toll‐like receptor 9 and produced more IL‐12 compared to iNDC. The data demonstrate a critical role played by DC in infection‐mediated inhibition of allergic responses.
Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus
Authors: Wald Ori , Pappo Orit , Safadi Rifaat , Dagan‐Berger Michal , Beider Katia , Wald Hanna , Franitza Suzanna , Weiss Ido , Avniel Shani , Boaz Pal , Hanna Jacob , Zamir Gidi , Eid Ahmed , Mandelboim Ofer , Spengler Ulrich , Galun Eithan , Peled Amnon 
Published: March 2004

AbstractChronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV‐ and HBV‐associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver‐infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re‐distribution of CXCL12 in the liver. Moreover, CXCL12 is up‐regulated in the endothelium of neo‐blood‐vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.
Positive and negative regulation of Fcϵ receptor I‐mediated signaling events by Lyn kinase C‐terminal tyrosine phosphorylation
Authors: Tolar Pavel , Dráberová Lubica , Tolarová Helena , Dráber Petr 
Published: March 2004

AbstractAlthough it is known that the Src family tyrosine kinase Lyn initiates Fcϵ receptor I (FcϵRI) signaling by phosphorylation of the receptor subunits, regulation of Lyn kinase activity and its consequences for receptor signaling are incompletely understood. Using a phospho‐Lyn‐specific antiserum, we show an increased phosphorylation of the Lyn C‐terminal regulatory tyrosine and decreased Lyn kinase activity during FcϵRI‐mediated mast cell activation. Mutant Lyn, defective in the C‐terminal tyrosine, constitutively phosphorylated several substrates in resting cells, but did not cause FcϵRI internalization or spontaneous degranulation. FcϵRI‐induced signaling in the presence of constitutively active Lyn exhibited enhanced phosphorylation of the receptor subunits, Syk, LAT, Gab2, phospholipase C (PLC)γ1 and PLCγ2, and production of phosphatidylinositol 3,4,5‐trisphosphate. Although enzymatic activities of PLCγ1 and PLCγ2 were also up‐regulated, amounts of inositol 1,4,5‐trisphosphate, mobilization of intracellular calcium and degranulation were suppressed. Additionally, constitutively active Lyn was strikingly less efficient than wild‐typeLyn in restoring the receptor‐mediated calcium responses in bone marrow mast cells derived from Lyn–/– mice. These findings pinpoint the tight regulation of Lyn kinase activity as a critical event in mast cell degranulation.