bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the α1β1 integrin complex in collagen gel contraction in vitro by fibroblasts
Authors: Carver Wayne , Molano Ivan , Reaves Titus A. , Borg Thomas K. , Terracio Louis 
Published: February 2005

AbstractMatrix remodeling, critical to embryonic morphogenesis and wound healing, is dependent on the expression of matrix components, their receptors, and matrix proteases. The collagen gel assay has provided an effective model for the examination of the functional role(s) of each of these groups of molecules in matrix remodeling. Previous investigations have indicated that collagen gel contraction involves the β1 integrin family of matrix receptors and is stimulated by several growth factors, including TGF‐β, PDGF, and angiotensin II. In particular, collagen gel remodeling by human cells involves the α2β1 and, to a lesser extent the α1β1 integrin complexes. The present studies were undertaken to determine the role of the α1 integrin chain, a collagen/laminin receptor, in collagen gel contration by rodent and avian fibroblasts. A high degree of correlation was found between the expression of the α1β1 integrin complex and the relative ability of cells to contract collagen gels. Further studies using antibodies and antisense oligonucleotides against the α1 integrin indicated a significant role for this integrin chain in contraction of collagen gels by rat cardiac fibroblasts. In addition, antibodies to the α1 integrin chain inhibited migration of these fibroblasts on a collagen substratum, suggesting that at least one role of this integrin is in migration of cells in collagen gels. These results indicate that the α1β integrin complex plays a significant role in cellular interactions with interstital collagen that are involved in matrix remodeling such as is seen during morphogenesis and wound healing. © 1995 Wiley‐Liss, Inc.
Fibroblast growth factor receptors 1 and 2 are differentially regulated in murine embryonal carcinoma cells and in response to fibroblast growth factor‐4
Authors: Ali Jahanara , Mansukhani Alka , Basilico Claudio 
Published: February 2005

AbstractWe have studied the expression of two of the receptors for fibroblast growth factors, FGFR‐1 and FGFR‐2, in response to ligand binding and in embryonal carcinoma (EC cells)> Exposure of mouse fibroblasts to FGF‐4 or FGF‐2 results in a drastic downregulation of the mRNA levels for FGFR‐2, while expression of FGER‐1 mRNA appears unaffected. Furthermore, FGF‐4 transformed cells display low levels of FGFR‐2 mRNA and these levels are significantly increased by treatment with anti FGF‐4 neutralizing antibodies. In undifferentiated F9 EC cells, the levels of FGFR‐2 mRNA are very low and increase substantially upon induction of differentiation. The level of mRNA for FGFR‐1 are again unaffected. To gain information on the regulation of expression of the gene encoding FGFR‐2 (bek) we have cloned the FGFR‐2 promoter region and used it to drive the expression of plasmids encoding the bacterial CAT enzyme. Transfection of these plasmids into FGF treated and untreated cells did not produce significant variation in CAT activity, suggesting that FGFR‐2 downregulation in response to ligand binding occurs mainly by a post‐transcriptional mechanism. In contrast, plasmids containing as little as 140 nt of the FGFR‐2 promoter region were regulated in F9 cells, showing substantially higher expression in differentiated than in undifferentiated cells. It appears therefore that FGFR‐2 expression in fibroblasts and EC cells is regulated by somewhat different mechanisms. In contrast, FGFR‐1 expression does not vary substantially under the conditions shown to affect FGFR‐2 expression. The implications of these findings are discussed. © 1995 Wiley‐Liss, Inc.
Growth control and gene expression in a new hepatocellular carcinoma cell line, Hep40: Inhibitory actions of vitamin K
Authors: Bouzahzah Boumediene , Nishikawa Yuji , Simon Daniela , Carr Brian I. 
Published: February 2005

AbstractThe growth characteristics of a newly established cell line, Hep40, derived from a human hepatoma are described. An absolute requirement was found for serum to mediate cell growth. Neither EGF, TGF‐α, nor HGF altered cell growth in the presence or absence of serum. A partial suppression of cell growth was achieved by several TGF‐β family proteins. Affinity crosslinking gels using 125I‐labeled TGF‐β showed a significant decrease in the TGF‐β cell‐surface type II receptor in Hep40 cells, compared to the TGF‐β‐sensitive Hep3B cell line. However, growth could be completely suppressed by addition of vitamins K to the culture medium in both Hep40 and several other hepatoma cell lines. Growth suppression by vitamins K was accompanied by an increased level of transcripts for c‐myc, c‐jun, and prothrombin genes, in contrast to the actions of TGF‐β1 protein, which caused a decrease in the level of c‐myc transcripts. These data show that this new human hepatoma cell line has partial resistance to growth inhibition by TGF‐β with a unique TGF‐β receptor defect. However, growth was completely suppressed by vitamins K. The differing gene expression patterns in response to TGF‐β as compared to vitamin K suggest that these two growth inhibitors act through differing pathways. © 1995 Wiley‐Liss Inc.
Plasma membrane‐dependent activation of gelatinase A in human vascular endothelial cells
Authors: Lewalle J. M. , Munaut C. , Pichot B. , Cataldo D. , Baramova E. , Foidart J. M. 
Published: February 2005

AbstractThe initiation of the angiogenic process requires a locally confined and time‐limited proteolysis of the basement membrane (BM) components at the site of new vessel sprout. Gelatinase A, a member of the matrix metalloproteinase family, degrades BM type IV collagen and is involved in the BM breakdown by migrating tumor cells and endothelial cells (EC). Gelatinase A is synthesized as latent proenzyme and must be activated in order to express its proteolytic activity. A plasma membrane‐dependent mechanism of activation has been described for several tumor and transformed cell lines. In the present study, we show that latent (72 kD) and mature (62‐59 kD) froms of gelatinase A are present in EC membrane fraction from Triton X‐114 extract while only latent form is found in the cytosolic fraction. The incubation of EC membrane fraction with exogenous latent gelatinase A resulted in a significant activation giving rise to 62–59 kD mature forms. 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a strong potentiator of angiogenesis in vitro and in vivo, increases the amount of both latent and activated forms of gelatinase A in EC membrane fraction as well as the ability of this latter fraction to activate exogenous latent gelatinase A. We show that the mRNA transcript coding for the membrane‐integrated MMP, the MT‐MMP, previously described as a potential gelatinase A activator in invasive tumor cells is also expressed in vascular EC and is regulated through a TPA sensitive process. This enzyme may be responsible for membrane‐dependent gelatinase A activation in normal vascular EC and may therefore be a determinant in the control of BM proteolysis during angiogenesis. © 1995 Wiley‐Liss Inc.
Serine proteinase inhibitors in human skeletal muscle: Expression of β‐amyloid protein precursor and α1‐antichymotrypsin in vivo and during myogenesis in vitro
Authors: Akaaboune Mohammed , Verdière‐Sahuqué Martine , Lachkar Sylvie , Festoff Barry W. , Hantaï Daniel 
Published: February 2005

AbstractThe balance of serine proteases and inhibitors in nerve and muscle is altered during programmed‐ and injury‐induced remodeling. A serpin, α1‐antichymotrypsin (α1‐ACT), and Kunitz‐inhibitor containing forms of the β‐amyloid precursor protein (βAPP) may be important components of this balance. In the present study, we analyzed their expression in primary cultures of human myogenic (satellite) cells that mimic myogenic differentiation using Western blotting and immunocytochemistry. In vitro results were compared to in vivo results from normal adult human skeletal muscle biopsies. Using an anti‐α1‐ACT polyclonal antibody, we detected a 62 kDa immunoreactive band both in cultured human myogenic cells (mononucleated myoblasts as well as multi‐nucleated myotubes) and in extracts of human muscle biopsies. With a polyclonal anti‐βAPP antibody we found two bands (105 and 120 kDa) in myoblasts and myotubes in culture. However, the same antibody recognized only a single band at 92 kDa in biopsies. By immunocytochemistry, both α1‐ACT and βAPP were indistinctly present on localized to the surface of myoblasts in culture. In contrast, these inhibitors were dense on myotube surfaces, where they often formed distinct aggregates and frequently co‐localized. In permeabilized muscle cells, α1‐ACT and βAPP appeared to be localized to the perikarya of both myoblasts and myotubes. Confirming previous results, both α1‐ACT and βAPP were present at the neuromuscular junction in human muscle sections. These developmental changes found during in vitro myogenesis for α1‐ACT and βAPP, both serine protease inhibitors, reinforce the hypothesis that regulation of the serine proteases and serine protease inhibitors plays an important role in neuromuscular differentiation. © 1995 Wiley‐Liss Inc.
Prostaglandin E2 regulates production of plasminogen activator isoenzymes, urokinase receptor, and plasminogen activator inhibitor‐1 in primary cultures of rat calvarial osteoblasts
Authors: Allan Elizabeth H. , Martin T. John 
Published: February 2005

AbstractThe bone resorbing agent, prostaglandin E2 (PGE2), was found to alter several components of the plasminogen activator (PA)/plasmin pathway in primary cultures of rat neonatal osteoblast‐like cells. The mRNA and activities of both urokinase‐type PA (uPA) and tissue‐type PA (tPA) were enhanced by PGE2 treatment. The presence of mRNA for the uPA receptor (uPAR) has been demonstrated in these cells and steady‐state levels shown to be greatly enhanced, the response being rapid and sustained for at least 24 hours. mRNA for plasminogen activator inhibitor 1 (PAI‐1) was modulated in a biphasic manner, with inhibition of the constitutive level apparent at 4 hours of treatment and stimulation apparent at 12 hours and longer, while PAI‐1 protein, measured by an ELISA assay for rat PAI‐1, was diminished over this period. Neither PAI‐2 mRNA nor mRNA for the broad spectrum protease inhibitor, protease nexin‐1 (PN‐1), was found to be modulated by PGE2. Therefore, PGE2 is likely to stimulate cell surface proteolytic activity, since uPA mRNA and cell‐associated activity were elevated, as was mRNA for the cellular receptor for uPA. Although it was not possible to measure uPAR number and affinity it seems likely that elevated uPAR mRNA would translate into increased uPARs which would localize the increased uPA activity to the pericellular region. tPA mRNA and activity were also increased transiently with the activity inhibited with prolonged incubations, apparently by PAI‐1. Elevation of tPA mRNA and activity may result in elevated activity within the extracellular matrix as tPA has been reported to associate with several matrix proteins. Thus the early effect of PGE2 would be to promote proteolysis, both pericellularly and in the extracellular matrix. The inhibition of PAI‐1 mRNA and protein, which would contribute to the elevation of activity, is due to PGE2, but the later stimulatory effect on PAI‐1 mRNA may be due to feedback regulation by transforming growth factor beta (TGFβ), secreted by osteoblasts and activated by elevated levels of PA. © 1995 Wiley‐Liss Inc.
IL‐3 and ribavirin induce differentiation and growth suppression during long‐term treatment of a megakaryocytic leukemia cell line
Authors: Majumdar Alokes , Kerby Stephen , Mullikin Brian , Beckstead Jay H. , Stenberg Paula E. , Seidman Michael M. 
Published: February 2005

AbstractDifferentiation of the megakaryocytic leukemia cells, CMK, was induced by long‐term (12 day) treatment with the combination of IL‐3 and the nucleoside analogue ribavirin (RV), which reduces cellular GTP levels. In a previous report we demonstrated the induction of early messages and antigens, as well as the formation of giant polyploid cells in the cultures (Majumdar et al., 1994, J. Cell. Physiol., 160:29–39). Here we show high level induction of messages for the late markers, Platelet Factor 4, GMP140 (P‐Selectin), thrombospondin, and beta thromboglobulin. The induced cells are also positive for these antigens by immunocytochemical analysis. The high level message induction resulted from synergy between the inducers. Pretreatment of the cells with IL‐3 could accelerate the rise in message seen with the inducer combination. The increase in differentiation markers was accompanied by a reduction of the proliferative capacity of the cells. Riboguanosine, which has anti differentiation activity, blocked the induction of early and late antigens by the inducer combination, and also by IL‐3 acting alone, but did not block the reduction in proliferative competence. In this model of megakaryocytic differentiation IL‐3 treatment yields and initial stimulation of growth followed by growth supperssion, and is the principal driver of the differentiation process. RV functions primarily as a stimulator of message and protein expression in synergy with IL‐3. © 1995 Wiley‐Liss Inc.
Exogenous nitric oxide elicits chemotaxis of neutrophils in vitro
Authors: Beauvais Francis , Michel Laurence , Dubertret Louis 
Published: February 2005

AbstractNitric oxide (NO) has been shown to be both an intercellular and intracellular messenger. We propose here that exogenous NO induces chemotactic locomotion of human neutrophils. Indeed, when human neutrophils were placed in a gradient of a nitric oxide donor (S‐nitroso‐N‐acetylpenicillamine; SNAP), a directed locomotion was induced, as evidenced by experiments of chemotaxis under agarose. Degraded SNAP (i.e., SNAP solution which had previously released NO) did not induce directed locomotion. Moreover, oxyhemoglobin, a scavenger of free NO, suppressed the chemotactic effect of SNAP, whereas LY‐83583, a soluble guanylate cyclase inhibitor, inhibited the SNAP‐mediated chemotaxis in a dose‐response manner. Other unrelated NO donors, SIN‐1 and S‐nitroso‐cysteine—a natural S‐nitroso‐compound, also induced a directed locomotion of neutrophils. Taken together, these in vitro experiments indicate that exogenous NO could mediate the chemotaxis of neutrophils and thus suggest that NO could contribute to neutrophil recruitment in vivo. © 1995 Wiley‐Liss Inc.
Interleukin‐10 selectively inhibits osteoclastogenesis by inhibiting differentiation of osteoclast progenitors into preosteoclast‐like cells in rat bone marrow culture system
Authors: Xu Li Xin , Kukita Toshio , Kukita Akiko , Otsuka Takeshi , Niho Yoshiyuki , Iijima Tadahiko 
Published: February 2005

AbstractRecombinant human interleukin‐10 (hIL‐10) inhibited the formation of osteoclast‐like multinucleated cells in rat whole bone marrow cultures. The effect of hIL‐10 on the process of osteoclast formation was further examined, since the process of osteoclast formation includes the proliferation and the differentiation of osteoclast progenitors into mononuclear preosteoclasts and the fusion of preosteoclasts into multinucleated osteoclasts. In the nonadherent bone marrow cell culture system, which was free of stromal cells and formed preosteoclast‐like cells, hIL‐10 significantly inhibited the formation of preosteoclast‐like cells even at a very low concentration (0.5 U/ml). The strong inhibition appeared even after treatment with hIL‐10 for only the first 24 h of the culture. However, hIL‐10 did not affect the fusion process of preosteoclast‐like cells to form osteoclast‐like multinucleated cells in the rat coculture system of preosteoclast‐like cells with primary osteo‐blasts. Furthermore, hIL‐10 completely inhibited the colony formation induced by granulocyte macrophage colony‐stimulating factor (GM‐CSF). These findings suggest that the inhibition of osteoclastogenesis by hIL‐10 started at the early stage of the differentiation of osteoclast progenitors to preosteoclasts. © 1995 Wiley‐Liss Inc.
Heparin binding, internalization, and metabolism in vascular smooth muscle cells: I. Upregulation of heparin binding correlates with antiproliferative activity
Authors: Letourneur Didier , Caleb Benjamin L. , Castellot John J. 
Published: February 2005

AbstractVascular smooth muscle cell (SMC) hyperplasia is an important component in the pathogenesis of arteriosclerotic lesions and is responsible for the failure of many vascular surgical procedures. SMC proliferation is inhibited by the glycosaminoglycan heparin; however, the precise mechanisms of action are still not understood. One important question in this regard is whether binding, internalization, and metabolism of heparin are necessary for the antiproliferative activity. In this study, we have analyzed SMC rendered resistant to the antiproliferative effect of heparin by drug selection and retroviral infection of SMC. We first examined the ability of heparin to bind to SMC. Experiments using [3H]heparin indicate the presence of saturable, heparin‐displaceable, protease‐sensitive binding sites on both sensitive and resistant SMC. The affinity of heparin binding does not correlate with the antiproliferative response. Using fluorescent and radiolabeled heparin probes, we observed that early heparin internalization kinetics in both sensitive and resistant SMC is similar, indicating that resistanace to heparin is not due to changes in the ability of cells to take up heparin. In contrast, we observed during the continuous incubation with heparin that binding to resistant SMC is rapidly downregulated, whereas sensitive cells continue to bind and internalize heparin. These results suggest that upregulation of heparin binding to the SMC surface is required for an antiproliferative response. In an accompanying paper (Letourneur et al. [1995] J. Cell. Physiol., 165:687–695, this issue), we describe the degradation and secretion of internalized heparin in both sensitive and resistant SMC. © 1995 Wiley‐Liss Inc.
Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: Results of the first US randomized, double‐blind, placebo‐controlled study
Authors: Truong Daniel , Duane Drake D. , Jankovic Joseph , Singer Carlos , Seeberger Lauren C. , Comella Cynthia L. , Lew Mark F. , Rodnitzky Robert L. , Danisi Fabio O. , Sutton James P. , Charles P. David , Hauser Robert A. , Sheean Geoffrey L. 
Published: February 2005

AbstractBotulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double‐blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10‐point vs. 3.8‐point reduction in total score, respectively, at week 4; P ≤ 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02–0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well‐tolerated in patients with cervical dystonia. © 2005 Movement Disorder Society
Normalising the associative law: An experiment with Martin-Löf's type theory
Authors: Hedberg Michael 
Published: February 2005

AbstractMartin-Löf's type theory contains a logic, a specification language and a programming language, so it is a tool with different uses. Although it is traditionally used as anintegratedprogramming logic, it may well be used as anexternallogic, which is necessary if one wants to use the formalism of type theory to verify the correctness of an external program. Different tools, such as well founded recursion, measure functions, or the separation of correctness into termination and partial correctness, may be used to obtain a correct type theory program. Type theory is viewed as anopensystem with respect toinductively definedtypes and predicates, which makes it easy to represent an external program as agraph. Formal proofs have been edited using Larry Paulson's ISABELLE.
Constitutively Elevated Salicylic Acid Signals Glutathione-Mediated Nickel Tolerance in Thlaspi Nickel Hyperaccumulators
Authors: Freeman John L. , Garcia Daniel , Kim Donggiun , Hopf Amber , Salt David E. 
Published: February 2005

Abstract
Progress is being made in understanding the biochemical and molecular basis of nickel (Ni)/zinc (Zn) hyperaccumulation in Thlaspi; however, the molecular signaling pathways that control these mechanisms are not understood. We observed that elevated concentrations of salicylic acid (SA), a molecule known to be involved in signaling induced pathogen defense responses in plants, is a strong predictor of Ni hyperaccumulation in the six diverse Thlaspi species investigated, including the hyperaccumulators Thlaspi goesingense, Thlaspi rosulare, Thlaspi oxyceras, and Thlaspi caerulescens and the nonaccumulators Thlaspi arvense and Thlaspi perfoliatum. Furthermore, the SA metabolites phenylalanine, cinnamic acid, salicyloyl-glucose, and catechol are also elevated in the hyperaccumulator T. goesingense when compared to the nonaccumulators Arabidopsis (Arabidopsis thaliana) and T. arvense. Elevation of free SA levels in Arabidopsis, both genetically and by exogenous feeding, enhances the specific activity of serine acetyltransferase, leading to elevated glutathione and increased Ni resistance. Such SA-mediated Ni resistance in Arabidopsis phenocopies the glutathione-based Ni tolerance previously observed in Thlaspi, suggesting a biochemical linkage between SA and Ni tolerance in this genus. Intriguingly, the hyperaccumulator T. goesingense also shows enhanced sensitivity to the pathogen powdery mildew (Erysiphe cruciferarum) and fails to induce SA biosynthesis after infection. Nickel hyperaccumulation reverses this pathogen hypersensitivity, suggesting that the interaction between pathogen resistance and Ni tolerance and hyperaccumulation may have played a critical role in the evolution of metal hyperaccumulation in the Thlaspi genus.
Aquaporins of the PIP2 Class Are Required for Efficient Anther Dehiscence in Tobacco
Authors: Bots Marc , Vergeldt Frank , Wolters-Arts Mieke , Weterings Koen , van As Henk , Mariani Celestina 
Published: February 2005

Abstract
Several processes during sexual reproduction in higher plants involve the movement of water between cells or tissues. Before flower anthesis, anther and pollen dehydration takes place before the release of mature pollen at dehiscence. Aquaporins represent a class of proteins that mediates the movement of water over cellular membranes. Aquaporins of the plasmamembrane PIP2 family are expressed in tobacco (Nicotiana tabacum) anthers and may therefore be involved in the movement of water in this organ. To gain more insight into the role these proteins may play in this process, we have analyzed their localization using immunolocalizations and generated plants displaying RNA interference of PIP2 aquaporins. Our results indicate that PIP2 protein expression is modulated during anther development. Furthermore, in tobacco PIP2 RNA interference plants, anther dehydration was slower, and dehiscence occurred later when compared with control plants. Together, our results suggest that aquaporins of the PIP2 class are required for efficient anther dehydration prior to dehiscence.