bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts
Authors: Glenjen Nils , Ersvær Elisabeth , Ryningen Anita , Bruserud Øystein 
Published: May 2004

AbstractBone marrow stromal cells constitute a heterogeneous population, and in the present study we investigated intercellular crosstalk via release of soluble mediators between native human AML blasts and fibroblasts/osteoblasts. Coculture of nonleukemic stromal cells and AML blasts separated by a semipermeable membrane decreased proliferation of the fibroblast line HFL1, and the inhibition was maintained when HFL1 and AML cells were cultured in direct contact. A similar inhibitory effect was observed for osteoblastic sarcoma cell lines (Cal72, SJSA‐1) and normal osteoblasts. GM‐CSF was released by both nonleukemic cells and a subset of AML blast populations, and increased levels of GM‐CSF were detected in AML cocultures with fibroblasts and osteoblastic sarcoma cells when testing AML cell populations with constitutive GM‐CSF release. Furthermore, constitutive IL‐1β secretion by AML blasts was detected only for a subset of patients, whereas relatively high levels of IL‐1RA were observed for all patients; coculture of AML blasts with HFL1 fibroblasts and osteoblastic sarcoma cells increased IL‐1β levels for patients with constitutive IL‐1β secretion, whereas IL‐1RA levels were slightly decreased but still generally higher than IL‐1β levels (tested only for HFL1 fibroblasts). The bidirectional crosstalk between AML blasts and stromal cells with increased release of AML growth factors may be important in leukemogenesis, whereas the decreased stromal cell proliferation combined with the persistent release of IL‐1RA may in addition inhibit remaining normal hematopoiesis and thereby contribute to bone marrow failure in AML. © 2004 Wiley‐Liss, Inc.
Dietary agent indole‐3‐carbinol protects female rats against the hepatotoxicity of the antitumor drug ET‐743 (trabectidin) without compromising efficacy in a rat mammary carcinoma
Authors: Donald Sarah , Verschoyle Richard D. , Greaves Peter , Colombo Tina , Zucchetti Massimo , Falcioni Cristiano , Zaffaroni Marco , D'Incalci Maurizio , Manson Margaret M. , Jimeno Jose , Steward William P. , Gescher Andreas J. 
Published: May 2004

AbstractET‐743, an experimental antitumor drug with promising activity in sarcoma, breast and ovarian carcinoma, is currently under phase 2 clinical evaluation. It is hepatotoxic in animals and patients. We tested the hypothesis that indole‐3‐carbinol (I3C), the hydrolysis product of glucosinolates occurring in cruciferous vegetables, may protect against ET‐743‐induced hepatotoxicity in the female Wistar rat, the animal species with the highest sensitivity toward the adverse hepatic effect of this drug. Hepatotoxicity was adjudged by measurement of plasma levels of bilirubin, alkaline phosphatase (ALP) and aspartate aminotransferase (AST) and by liver histopathology. The effect of I3C on the kinetics of ET‐743 in rat plasma and liver was investigated by high‐pressure liquid chromatography. The effect of I3C on the antitumor efficacy of ET‐743 was explored in rats bearing the 13762 mammary carcinoma. ET‐743 (40 μg/kg i.v.) alone caused an elevation of plasma bilirubin, ALP and AST levels and degeneration and patchy focal necrosis of bile duct epithelial cells. Addition of I3C to the diet (0.5%) for 6 days prior to ET‐743 administration almost completely abolished manifestations of hepatotoxicity. In contrast, a dietary concentration of 0.1% I3C did not protect, nor did dietary diindolylmethane (0.2%), an acid‐catalyzed condensation product of I3C. Ingestion by rats of I3C for 6 days prior to ET‐743 (40 μg/kg i.v.) decreased plasma but not hepatic concentrations of ET‐743 compared to animals that received ET‐743 alone. I3C did not interfere with the antitumor efficacy of ET‐743. The results suggest that ingestion of I3C may counteract the unwanted effect of ET‐743 in the liver. I3C should be investigated as a hepatoprotectant in patients who receive ET‐743 therapy. © 2004 Wiley‐Liss, Inc.
Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients
Authors: Osman Iman , Kang Melissa , Lee Andy , Deng Fang‐Ming , Polsky David , Mikhail Maryann , Chang Caroline , David Dexter A. , Mitra Nandita , Wu Xue‐Ru , Sun Tung‐Tien , Bajorin Dean F. 
Published: May 2004

AbstractOur purpose was to determine the clinical relevance of the detection of circulating tumor cells (CTCs) expressing urothelial and epithelial markers in bladder cancer patients. Sixty‐two patients who presented to Memorial Sloan‐Kettering Cancer Center between July 2000 and September 2001 were studied. Peripheral blood was tested by nested RT‐PCR assay for uroplakins (UPs) Ia, Ib, II and III as well as for epidermal growth factor receptor (EGFR). We determined the sensitivity and specificity of each individual marker and the combinations of UPIa/UPII and UPIb/UPIII. The latter strategy was based on our data, which showed that UPIa and UPIb form heterodimers with UPII and UPIII, respectively. Forty patients had clinically advanced bladder cancer and 22 had no evidence of disease at the time of assay. Eight of the 22 patients recurred during the follow‐up period. All 8 patients were positive at presentation for UPIa/UPII. The combination of UPIa/UPII provided the best sensitivity (75%) of detecting CTCs, with a specificity of 50%. The combination of UPIb/UPIII was the most specific (79%) but had modest sensitivity (31%). Detection of EGFR‐positive cells alone and in combination with UPs was inferior to that for UPIa/UPII. Combinations of urothelial markers are superior to single urothelial or epithelial markers in detecting CTCs in bladder cancer patients. Further efforts are under way to confirm the potential predictive value of these markers in a prospectively designed study of a larger cohort of patients. © 2004 Wiley‐Liss, Inc.
Viscoelastic characterizations of acellular dermal matrix (ADM) preparations for use as injectable implants
Authors: Ho Hsiu‐O , Tsai Yu‐Ting , Chen Ray‐Neng , Sheu Ming‐Thau 
Published: May 2004

AbstractViscoelastic characteristics of acellular dermal matrix (ADM) preparations with various additives were analyzed with creep curves, stress–strain relationships, and the storage modulus with reference to those of ADM preparations crosslinked with glutaraldehyde. Creep curves for all ADM preparations were determined to comply with the Kelvin–Voigt model. The stress–strain plots of all ADM preparations compared were described as linear. The storage modulus of all ADM preparations was maintained at a nearly constant level throughout the range of oscillating frequencies applied. ADM preparations crosslinked with glutaraldehyde showed that both Young's modulus (E) for the spring part and retardation time (τ) in the Kelvin–Voigt model, and hence viscosity (η) for the liquid part, increased with an increasing concentration of glutaraldehyde. Higher Young's modulus and viscosity and a greater extent of the “solid” response of ADM preparations crosslinked with glutaraldehyde might have been responsible for the longer persistence that was demonstrated after implantation. The increase in ADM concentration and the addition of various additives to ADM preparations, including α‐hydroxy acid (citric acid, lactic acid, and glycolic acid) and hyaluronic acid, resulted in similar effects on the viscoelastic characteristics of the ADM preparations, but they were less efficacious than those crosslinked with glutaraldehyde. Among them, increasing ADM concentration to >200 mg/mL and addition of glycolic acid at a concentration of >2% improved the viscoelastic characteristics of the resulting ADM preparations so that their level of persistence was closer to that of material crosslinked with glutaraldehyde. On the contrary, the influence on viscoelastic characteristics of adding PVP greatly differed from that of hyaluronic acid and was only apparent when adding concentrations of PVP of >10%. Similarly, viscoelastic characteristics of the ADM preparations examined were also so sensitive to temperature that the persistence of ADM preparations after implantation at body temperature would deteriorate. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 83–96, 2004
Prolonged ectopic calcification induced by BMP‐2–derived synthetic peptide
Authors: Saito Atsuhiro , Suzuki Yoshihisa , Ogata Shin‐Ichi , Ohtsuki Chikara , Tanihara Masao 
Published: May 2004

AbstractBone morphogenetic protein‐2 (BMP‐2) promotes the formation and regeneration of bone and cartilage, and therefore constitutes the most promising candidate for a bone repair material. However, it also has a wide range of functions, such as in organogenesis and apoptosis. Therefore, we investigated a novel synthetic peptide corresponding to residues 73–92 of BMP‐2. This peptide bound to a BMP‐2‐specific receptor and elevated both alkaline phosphatase activity and osteocalcin mRNA in the murine cell line, C3H10T1/2. The 73–92 peptide also induced ectopic calcification when conjugated to a covalently crosslinked alginate gel. Here we report that the 73–92 peptide‐conjugated alginate gel showed prolonged ectopic calcification for up to 7 weeks in rat calf muscle. In contrast, rhBMP‐2‐impregnated collagen gel showed maximum ectopic calcification at 3 weeks, and the calcified products that had formed disappeared after 5 weeks. Histological examination showed that the 73–92 peptide‐conjugated alginate gel induced many osteoblast‐like cells and few osteoclasts. In contrast, rhBMP‐2‐impregnated collagen gel induced many osteoclasts. These results suggest that the 73–92 peptide on alginate gel remains active at the implanted site, continuously induces differentiation of osteoblast precursor cells into osteoblasts, and activates osteoblasts to promote ectopic calcification. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 115–121, 2004
Influence of additive hyaluronic acid on the lubricating ability in the temporomandibular joint
Authors: Kawai Nobuhiko , Tanaka Eiji , Takata Takashi , Miyauchi Mutsumi , Tanaka Masao , Todoh Masahiro , van Eijden Theo , Tanne Kazuo 
Published: May 2004

AbstractIn synovial fluid, hyaluronic acid (HA) is an essential component for the lubrication of joints, thus preventing friction. The relationship between HA and joint friction is not unambiguously established yet. In the present study, the effect of the application of HA on the frictional coefficient in the temporomandibular joint was evaluated. After measuring the frictional coefficient in intact porcine joints (n = 10), the subsequent effect of phosphate‐buffered saline (PBS) washing and gauze scouring and the application of HA was examined. Compared with the intact joint, the frictional coefficient was significantly larger after PBS washing and gauze scouring. Subsequent application of HA resulted in a significant decrease (50–75%) of the frictional coefficient. However, it did not recover to the same value as in the intact joints. Observations by scanning electron microscopy showed that after PBS washing, the amorphous layer of the articular cartilage was still intact, whereas it was partially collapsed after gauze scouring. In conclusion, the addition of HA did reduce the coefficient of friction under the experimental conditions in this study; the relevance to the clinical condition and the duration of the treatment effect in vivo require further investigation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 149–153, 2004
Opinions and trends in biomaterials education: Report of a 2003 Society for Biomaterials survey
Authors: Karp Jeffrey M. , Friis Elizabeth A. , Dee Kay C. , Winet Howard 
Published: May 2004

AbstractThe Society for Biomaterials (SFB) aims to serve its members through acting as a forum for the exchange of information and ideas. To aid in the practical development of the SFB and more specifically biomaterials education, all active, associate, and student members were surveyed. In general, the survey asked questions regarding respondent demographics, experiences and activities with the SFB, and opinions about biomaterials education. Perceptions and needs of biomaterials‐related education and career‐related training practices were a specific focus of the survey. A total of 140 individuals responded to the survey for a response rate of 18%. Members from industry felt that new hires, in general, should be better trained in product development, regulatory issues for new materials and devices, and in the relevant testing required. When asked what was missing from their professional education, many respondents commented that business training in areas such as negotiations, management, and understanding the needs outside of academia was lacking. Also, many respondents seemed to have trouble identifying with what they were supposed to know and felt a “lack of set professional knowledge.” This study has raised many ideas and questions that require further discussion. The results should ultimately be useful for helping the SFB decide how best to focus future efforts in biomaterials education. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 1–9, 2004
Transitions in replication timing in a 340 kb region of human chromosomal R‐Band 1p36.1
Authors: Brylawski Bruna P. , Cohen Stephanie M. , Horne Hisani , Irani Neville , Cordeiro‐Stone Marila , Kaufman David G. 
Published: May 2004

AbstractDNA replication is initiated within a few chromosomal bands as normal human fibroblasts enter the S phase (Cohen et al. [1998]: Exp Cell Res. 245:321–329). In the present study, we determined the timing of replication of sequences along a 340 kb region in one of these bands, 1p36.13, an R band on chromosome 1. Within this region, we identified a segment of DNA (approximately 140 kb) that is replicated in the first hour of the S phase and is flanked by segments replicated 1–2 h later. Using a quantitative PCR‐based assay to measure sequence abundance in size‐fractionated (900–1,700 nt) nascent DNA (Giacca et al. [1994]: Proc Natl Acad Sci USA. 91:7119), we mapped two functional origins of replication separated by 54 kb and firing 1 h apart. One origin was found to be functional during the first hour of S and was located within a CpG island associated with a predicted gene of unknown function (Genscan NT_004610.2). The second origin was activated in the second hour of S and was mapped to a CpG island near the promoter of the aldehyde dehydrogenase 4A1 (ALDH4A1) gene. At the opposite end of the early replicating segment, a more gradual change in replication timing was observed within the span of approximately 100 kb. These data suggest that DNA replication in adjacent segments of band 1p36.13 is organized differently, perhaps in terms of replicon number and length, or rate of fork progression. In the transition areas that mark the boundaries between different temporal domains, the replication forks initiated in the early replicated region are likely to pause or delay progression before replication of the 340 kb contig is completed. © 2004 Wiley‐Liss, Inc.
Backup pathways of NHEJ are suppressed by DNA‐PK
Authors: Perrault Ronel , Wang Huichen , Wang Minli , Rosidi Bustanur , Iliakis George 
Published: May 2004

AbstractIn cells of higher eukaryotes double strand breaks (DSBs) induced in the DNA after exposure to ionizing radiation (IR) are rapidly rejoined by a pathway of non‐homologous end joining (NHEJ) that requires DNA dependent protein kinase (DNA‐PK) and is therefore termed here D‐NHEJ. When this pathway is chemically or genetically inactivated, cells still remove the majority of DSBs using an alternative, backup pathway operating independently of the RAD52 epistasis group of genes and with an order of magnitude slower kinetics (B‐NHEJ). Here, we investigate the role of DNA‐PK in the functional coordination of D‐NHEJ and B‐NHEJ using as a model end joining by cell extracts of restriction endonuclease linearized plasmid DNA. Although DNA end joining is inhibited by wortmannin, an inhibitor of DNA‐PK, the degree of inhibition depends on the ratio between DNA ends and DNA‐PK, suggesting that binding of inactive DNA‐PK to DNA ends not only blocks processing by D‐NHEJ, but also prevents the function of B‐NHEJ. Residual end joining under conditions of incomplete inhibition, or in cells lacking DNA‐PK, is attributed to the function of B‐NHEJ operating on DNA ends free of DNA‐PK. Thus, DNA‐PK suppresses alternative pathways of end joining by efficiently binding DNA ends and shunting them to D‐NHEJ. © 2004 Wiley‐Liss, Inc.
TGF‐β1 enhances βig‐h3‐mediated keratinocyte cell migration through the α3β1 integrin and PI3K
Authors: Jeong Ha‐Won , Kim In‐San 
Published: May 2004

Abstractβig‐h3 is an extracellular matrix (ECM) protein whose expression is highly induced by transforming growth factor beta1 (TGF‐β1). We previously demonstrated that βig‐h3 has two α3β1 integrin‐interacting motifs, which promote adhesion, migration, and proliferation of human keratinocytes. Both βig‐h3 and TGF‐β1 have been suggested to play important roles in the healing of skin wounds. In this study, we demonstrate that TGF‐β1 enhances keratinocyte adhesion and migration toward βig‐h3 through the α3β1 integrin. TGF‐β1 did not increase the amount of the α3β1 integrin on the cell surface, but rather increased its affinity for βig‐h3. LY294002, an inhibitor of PI3K, blocked the basal and TGF‐β1‐enhanced cell migration but not adhesion to βig‐h3. A constitutively active mutant of PI3K stimulated cell migration but not adhesion to βig‐h3. The PI3K pathway is also not associated with the affinity of the α3β1 integrin to βig‐h3. TGF‐β1 induced phosphorylation of AKT and FAK. Taken together, these data suggest that TGF‐β1 increases affinity of the α3β1 integrin to βig‐h3, resulting in enhanced adhesion and migration of keratinocytes toward βig‐h3. TGF‐β1 also enhances migration through PI3K, but PI3K is not associated with either the binding affinity of the α3β1 integrin or its adhesion to βig‐h3. © 2004 Wiley‐Liss, Inc.
Developmental expression of OAP‐1/Tspan‐3, a member of the tetraspanin superfamily
Authors: Tiwari‐Woodruff Seema K. , Kaplan Roman , Kornblum Harley I. , Bronstein Jeff M. 
Published: May 2004

AbstractOSP/claudin‐11‐associated protein (OAP‐1/Tspan‐3), originally isolated by yeast two‐hybrid screening using OSP/claudin‐11 (oligodendrocyte‐specific protein) as bait, is a member of the tetraspanin superfamily and OAP‐1/Tspan‐3, OSP/claudin‐11, and β1 integrin form a protein complex that seems to be involved in oligodendrocyte proliferation and migration. This study investigated the temporal and regional expression, glycosylation status, and tissue distribution of OAP‐1/Tspan‐3. OAP‐1/Tspan‐3 mRNA was expressed as a single transcript throughout brain development, with high levels of expression in the germinal zones. OAP‐1/Tspan‐3 protein contains N‐terminal glycosylation sites in extracellular loop 2 and deglycosylation studies indicated a decrease in apparent molecular weight of OAP‐1/Tspan‐3, consistent with removal of N‐glycans. Similar to OSP/claudin‐11, OAP‐1/Tspan‐3 is expressed in all stages of oligodendrocyte development and in the myelin sheath. Unlike OSP/claudin‐11, however, it is expressed in all cell types tested in the central nervous system (CNS), including neurons and astrocytes. The association of OAP‐1/Tspan‐3 with OSP/claudin‐11 and β1 integrin, its subcellular distribution as a cell surface, membrane‐spanning glycoprotein, and its widespread distribution supports its potential role in cell migration, proliferation, and interactions between cells and extracellular matrix. © 2004 Wiley‐Liss, Inc.
Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: Disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype
Authors: Neuhuber Birgit , Gallo Gianluca , Howard Linda , Kostura Lisa , Mackay Alastair , Fischer Itzhak 
Published: May 2004

AbstractBone marrow stromal cells (MSC), which represent a population of multipotential mesenchymal stem cells, have been reported to undergo rapid and robust transformation into neuron‐like phenotypes in vitro following treatment with chemical induction medium including dimethyl sulfoxide (DMSO; Woodbury et al. [2002] J. Neurosci. Res. 96:908). In this study, we confirmed the ability of cultured rat MSC to undergo in vitro osteogenesis, chondrogenesis, and adipogenesis, demonstrating differentiation of these cells to three mesenchymal cell fates. We then evaluated the potential for in vitro neuronal differentiation of these MSC, finding that changes in morphology upon addition of the chemical induction medium were caused by rapid disruption of the actin cytoskeleton. Retraction of the cytoplasm left behind long processes, which, although strikingly resembling neurites, showed essentially no motility and no further elaboration during time‐lapse studies. Similar neurite‐like processes were induced by treating MSC with DMSO only or with actin filament‐depolymerizing agents. Although process formation was accompanied by rapid expression of some neuronal and glial markers, the absence of other essential neuronal proteins pointed toward aberrantly induced gene expression rather than toward a sequence of gene expression as is required for neurogenesis. Moreover, rat dermal fibroblasts responded to neuronal induction by forming similar processes and expressing similar markers. These studies do not rule out the possibility that MSC can differentiate into neurons; however, we do want to caution that in vitro differentiation protocols may have unexpected, misleading effects. A dissection of molecular signaling and commitment events may be necessary to verify the ability of MSC transdifferentiation to neuronal lineages. © 2004 Wiley‐Liss, Inc.