bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of dietary, medical and lifestyle risk factors for incident kidney cancer in postmenopausal women
Authors: Nicodemus Kristin K. , Sweeney Carol , Folsom Aaron R. 
Published: November 2003

AbstractKidney cancer incidence rates in the United States have been increasing and are not fully accounted for by better diagnostic techniques. Risk factors in women are incompletely described. A total of 34,637 Iowan women initially free of cancer completed a mailed questionnaire in 1986. Kidney cancer incidence was identified over 15 years of follow‐up (n= 124) through linkage to a statewide cancer registry. Adjusted for age and other risk factors, kidney cancer was associated positively with maximum adult weight (pfor trend = 0.02) and current waist‐to‐hip ratio (pfor trend = 0.002). Compared to nondrinkers, consumers of alcohol of 3.0 or more grams per day had a relative risk (RR) of 0.52 (95% CI = 0.29–0.92). Total vitamin C intake was associated positively with risk of kidney cancer (pfor trend = 0.04), whereas total vitamin E intake was associated negatively with risk (pfor trend = 0.002). The few women who used copper supplements had a 6.52‐fold increase in risk of kidney cancer (95% CI = 1.95–21.8). Compared to never users, women who were former users of estrogen had an increased risk of kidney cancer (RR = 1.62; 95% CI = 1.11–2.36), but current users of estrogen were not at a higher risk. Women who were nulliparous or had more than 2 live births were also at increased risk of kidney cancer compared with women who had 1 or 2 live births. In conclusion, in these postmenopausal women, overweight, particularly central adiposity, was an important risk factor for kidney cancer. Potential risk factors that warrant further exploration were low intake of alcohol and vitamin E, higher intake of vitamin C, nulli‐ or multiparity and use of copper supplements. © 2003 Wiley‐Liss, Inc.
Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas
Authors: Tiemersma Edine W. , Bunschoten Annelies , Kok Frans J. , Glatt Hansruedi , de Boer Sybrand Y. , Kampman Ellen 
Published: November 2003

AbstractCigarette smoke contains polycyclic hydrocarbons and arylamines that may both be activated by sulfotransferase, encoded by SULT1A1. A genetic polymorphism leads to an Arg213His substitution, thereby decreasing enzyme activity and stability and might thus modify the association between smoking and colorectal adenomas. We investigated this in a Dutch case‐control study. Additionally, we evaluated potential roles of epoxide hydrolase (EPHX), N‐acetyltransferases (NAT1 and NAT2) and glutathione S‐transferases (GSTM1 and GSTT1). The data analysis included 431 adenoma cases and 432 polyp‐free controls (54% women; mean age, 54.6 years) enrolled at endoscopy in 8 Dutch hospitals between 1997 and 2000. All participants provided data on smoking habits and blood for DNA isolation. Genotyping was performed using appropriate polymerase chain reaction‐restriction fragment length polymorphism procedures. Multivariate models included age, sex, endoscopy indication, consumption of snacks and alcohol and, if appropriate, daily smoking dose or smoking duration. Smoking increased colorectal adenoma risk, most importantly by duration. Smoking for more than 25 years more than doubled adenoma risk (OR = 2.4, 95% CI = 1.4–4.1) compared to never smoking. Combinations of SULT1A1 fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification. We found no clear effects of the other genetic polymorphisms on the association between smoking and adenomas. We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association. © 2003 Wiley‐Liss, Inc.
Protective effect of green tea against prostate cancer: A case‐control study in southeast China
Authors: Jian Le , Xie Li Ping , Lee Andy H. , Binns Colin W. 
Published: November 2003

AbstractTo investigate whether green tea consumption has an etiological association with prostate cancer, a case‐control study was conducted in Hangzhou, southeast China during 2001–2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases, and matched to the age of cases. Information on duration, quantity and frequency of usual tea consumption, as well as the number of new batches brewed per day, were collected by face‐to‐face interview using a structured questionnaire. The risk of prostate cancer for tea consumption was assessed using multivariate logistic regression adjusting for age, locality, education, income, body mass index, physical activity, alcohol consumption, tobacco smoking, total fat intake, marital status, age at marriage, number of children, history of vasectomy and family history of prostate cancer. Among the cases, 55.4% were tea drinkers compared to 79.9% for the controls. Almost all the tea consumed was green tea. The prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumption. The adjusted odds ratio (OR), relative to non‐tea drinkers, were 0.28 (95% CI = 0.17–0.47) for tea drinking, 0.12 (95% CI = 0.06–0.26) for drinking tea over 40 years, 0.09 (95% CI = 0.04–0.21) for those consuming more than 1.5 kg of tea leaves yearly, and 0.27 (95% CI = 0.15–0.48) for those drinking more than 3 cups (1 litre) daily. The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer. © 2003 Wiley‐Liss, Inc.
Retargeting of adenoviral infection to melanoma: Combining genetic ablation of native tropism with a recombinant bispecific single‐chain diabody (scDb) adapter that binds to fiber knob and HMWMAA
Authors: Nettelbeck Dirk M. , Rivera Angel A. , Kupsch Jörg , Dieckmann Detlef , Douglas Joanne T. , Kontermann Roland E. , Alemany Ramon , Curiel David T. 
Published: November 2003

AbstractGene therapy is an emerging and promising modality for the treatment of malignant melanoma and other neoplasms for which conventional therapies are inadequate. Various therapeutic genes have shown promise for tumor cell killing. However, successful gene therapy depends on the development of efficient and targeted gene transfer vectors. Here we describe a novel strategy for targeting of adenovirus‐mediated gene transfer to melanoma cells. This strategy combines genetic ablation of native adenoviral tropism with redirected viral binding to melanoma cells via a bispecific adapter molecule, a bacterially expressed single‐chain diabody, scDb MelAd, that binds to both the adenoviral fiber protein and to the high molecular weight melanoma‐associated antigen (HMWMAA). This antigen is widely and specifically expressed on the surface of melanoma cells and its expression is associated with tumor development and progression. Our results showed specific and strong binding of the anti‐HMWMAA scFv RAFT3 and the bispecific adapter scDb MelAd to melanoma cells. In adenoviral infection experiments, we demonstrated i) substantially (>50‐fold) reduced infectivity of capsid mutant adenoviruses, ii) restored (up to 367‐fold increase), CAR‐independent and HMWMAA‐mediated infectivity of these mutant viruses by scDb MelAd specifically in melanoma cells, and iii) higher levels of transgene expression in melanoma cells by fiber mutant virus complexed with scDbMelAd, relative to a vector with wild‐type fibers. We confirmed the utility of this targeting strategy with human primary melanoma cells that represent clinically relevant substrates. These experiments established that the retargeting strategy mediates up to 54‐fold increased adenoviral gene transfer to CAR‐negative melanoma cells compared to the vector with native tropism. Hence, the HMWMAA‐targeted adenoviral vector lacking native tropism exhibits both enhanced specificity and augmented infectivity of gene transfer to melanoma cells, suggesting that it is feasible to use this vector to improve gene therapy for malignant melanoma. © 2004 Wiley‐Liss, Inc.
Osteogenic differentiation of cultured rat and human bone marrow cells on the surface of zinc‐releasing calcium phosphate ceramics
Authors: Ikeuchi Masako , Ito Atsuo , Dohi Yoshiko , Ohgushi Hajime , Shimaoka Hideki , Yonemasu Kunio , Tateishi Tetsuya 
Published: November 2003

AbstractRat and human bone marrow cells (BMCs) were cultured on a composite ceramic of zinc‐containing β‐tricalcium phosphate and hydroxyapatite (ZnTCP/HAP) with a (Ca+Zn)/P molar ratio of 1.60 and varying zinc contents. After a 2‐week culture of the BMCs in the presence of β‐glycerophosphate and dexamethasone, many macroscopic mineralized areas with high alkaline phosphatase (ALP) activity were seen on the ZnTCP/HAP ceramic disks. The ALP activity increased with increasing zinc content in the ceramics. The highest ALP activity was observed when the BMCs were cultured on the ceramics with 1.26 wt % zinc, and the ceramics released zinc ions at concentrations from 2.2 to 7.2 μg/mL into the culture medium. Zinc ions were incorporated into mineralized areas produced by BMCs. BMCs also were directly cultured onto the culture dish surface, and the addition of 100 μM of free ZnCl2 (6.5 μg/mL) to the culture medium significantly increased the ALP activity of the BMCs relative to the culture medium without the ZnCl2addition. The maximum zinc concentration required to enhance mineralization was higher in human BMCs than in rat BMCs. The present study demonstrates the superiority of ZnTCP/HAP ceramics over TCP/HAP in supporting the osteogenic differentiation of BMCs, and thus these ceramics are safe and useful in clinical settings, such as for bone reconstructive surgery. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1115–1122, 2003
Novel associated hydrogels for nucleus pulposus replacement
Authors: Thomas Jonathan , Lowman Anthony , Marcolongo Michele 
Published: November 2003

AbstractHydrogels of poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) blends may provide a material suitable for replacement of the nucleus pulposus of the intervertebral disc. This research examined the stability of these hydrogels under simulated physiological conditions. Polymer dissolution and stability were characterized over 120 days immersion, chemical surface analysis over 56 days immersion, and tensile mechanical behavior over 56 days immersion. Rubber elasticity theory was used by combining mechanical results with swelling data to calculate network characteristics such as the molecular weight between physical crosslinks and density of crosslinks. Properties were examined as a function of PVA/PVP composition as well as PVA molecular weight and PVP molecular weight. Results indicated that PVA/PVP blends prepared with moderate amounts of PVP (0.5–5%) resulted in a polymer network stabilized through interchain hydrogen bonding between hydroxyl groups on PVA chains and carbonyl groups on PVP chains. Most notably, a significant decrease in percentage of polymer mass loss was seen for blends prepared with 143K molecular weight PVA. Surface chemical analysis revealed that PVP unincorporated in the network structure suffered significant dissolution out of the polymer network and into solution. The molecular weight of PVA and PVP were shown to have a significant influence on the blends' network properties. Gels prepared with lower molecular weight PVA resulted in a more stable blend containing a higher density of crosslinks. However, blends prepared with a higher molecular weight PVA showed superior polymer network stability in dissolution studies. The blend that had the best combination of network stability under physiological conditions and a relatively tight, stable, and crosslinked network was prepared with 99% PVA (143K) and 1% PVP (40K). This material is proposed as an implant material for replacement of the degenerated nucleus pulposus. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1329–1337, 2003
Thermally reversible polymer gel for chondrocyte culture
Authors: Au Angela , Ha Jinny , Polotsky Anna , Krzyminski Karol , Gutowska Anna , Hungerford David S. , Frondoza Carmelita G. 
Published: November 2003

AbstractWe have evaluated a biomaterial to serve as a scaffold for the propagation and amplification of chondrocytes that promotes the original cellular phenotype of these cells. The goal of the present study was to investigate the use of thermally reversible polymer gels poly(NiPAAm‐co‐AAc), as a biocompatible supporting scaffold for the propagation of chondrocytic cells. The polymer gels at temperatures above its lower critical solution temperature whereas liquefying at temperatures below its lower critical solution temperature of 34.5°C. Hence, the polymer, in its gelled form, has the ability to hold cells in situ, forming a matrix similar to the natural cellular environment or the extracellular matrix that comprises cartilage. We tested the hypothesis that the polymer gel promotes cell viability and function. Human osteoblast‐like cells, nasal chondrocytes, and articular chondrocytes (1 × 105/150 μL) were resuspended in enriched Dulbecco's minimal essential media and were plated onto control (without gel) and gel containing 24‐well plates. The plates were reincubated at 37°C, 5% CO2 for the time point of interest. Additional media was added to the plates and exchanged as needed. After cell culture, cells were retrieved, enumerated, and cell viability was determined. Other aliquots of the cells were stained for morphological analysis whereas expression of chondrocyte markers including collagen type II and aggrecan were determined using reverse transcriptase–polymerase chain reaction. The polymer gel was not cytotoxic because the cell number retrieved from three‐dimensional culture gel was found to be one to two times higher than that retrieved from monolayer culture. Chondrocytes propagated in the thermo‐reversible polymers expressed enhanced or maintained expression of collagen type II and aggrecan. Collagen type I expression was decreased or unaltered. The N‐isopropylacrylamide and acrylic acid copolymer gel has potential use as a cell culture substrate and as a cell delivery vehicle. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1310–1319, 2003
In vitro evaluation of degradation and cytotoxicity of a novel composite as a bone substitute
Authors: Liu Bai‐Shuan , Yao Chun‐Hsu , Chen Yueh‐Sheng , Hsu Shan‐Hui 
Published: November 2003

AbstractThe purpose of this study was to prepare and evaluate in vitro the feasibility and cytocompatibility of a novel composite (GGT) as a large defect bone substitute. The composite is tricalcium phosphate ceramic particles combined with genipin crosslinked gelatin. After soaking the GGT composites in Ringer solutions at 37°C for 7, 14, 28, 42, 56, and 84 days, the in vitro biologic degradation rate and biocompatibility were determined. Substances released from soaked GGT composites were analyzed with an ultraviolet visible light spectrophotometer. In addition, the solution soaking the GGT was co‐cultured with osteoblasts to determine whether or not the released substances from GGT could facilitate the growth of bone cells. After they had been cultured for 2 days, the osteoblasts were tested for differentiation and proliferation by alkaline phosphatase (ALP) activity and a MTT assay. Results indicate that the concentration of the genipin solution is a critical factor in deciding the crosslinking degree of the GGT composite. Complete crosslinking reaction in the GGT composite occurred when 0.5 wt % of genipin had been added. Cytotoxic testing revealed that 80 ppm of the genipin in the culture medium served as the level over which cytotoxicity to osteoblasts could be produced. In addition, we found that gelatin and calcium continuously were released from the GGT composite in the soaking solution, which promoted differentiation and proliferation of the osteoblasts. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1163–1169, 2003
Fabrication and in vitro testing of polymeric delivery system for condensed DNA
Authors: Huang Yen‐Chen , Connell Maureen , Park Youmie , Mooney David J. , Rice Kevin G. 
Published: November 2003

AbstractPolyethylenimine (PEI) was combined with plasmid DNA and freeze dried following the addition of sucrose as a lyoprotectant and pore‐forming agent. Freeze‐dried PEI DNA condensates were dry mixed with granular polylactideglycolic acid (PLGA) then compression molded and sponged to encapsulated PEI DNA. A measurement of the elastic modulus indicated that 91 wt% sucrose substituted for 95 wt% sodium chloride as a porogen, resulting in PLGA sponges with a mechanical modulus of 100 kPa. The PEI DNA was retained (80%) within PLGA sponges prepared with sucrose during the leaching and subsequent 2‐week release studies, whereas sodium chloride PLGA sponges caused the premature release (100%) of PEI DNA within 2 days. In vitro gene transfer studies with PEI DNA PLGA sponges established that adherent and infiltrating fibroblasts expressed reporter gene for 15 days compared with the short, 3‐day expression mediated by direct gene of PEI DNA on cells in culture. The results demonstrate an approach to encapsulate condensed DNA in a PLGA sponge for the purpose of retaining DNA within the matrices and creating efficient gene transfer during tissue engineering. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1384–1392, 2003
Use of vascular endothelial cell growth factor gene transfer to enhance implantable sensor function in vivo
Authors: Klueh U. , Dorsky D. I. , Kreutzer D. L. 
Published: November 2003

AbstractIn the current study, we developed and validated a simple, rapid and safe in vivo model to test gene transfer and sensor function in vivo. Using the model, we tested the specific hypothesis that in vivo gene transfer of angiogenic factors at sites of biosensor implantation would induce neovascularization surrounding the sensor and thereby enhance biosensor function in vivo. As the in vivo site for testing of our gene transfer cell and biosensor function systems, the developing chorioallantoic membrane (CAM) of the embryo was utilized. Vascular endothelial cell growth factor (VEGF) was used as a prototype for angiogenic factor gene transfer. A helper‐independent retroviral vector derived from Rous sarcoma virus (RSV), designated RCAS, was used for gene transfer of the murine VEGF (mVEGF) gene (mVEGF:RCAS) into the DF‐1 chicken cell line (designated mVEGF:DF‐1). Initially, the ability of VEGF:DF‐1 cells to produce VEGF and RCAS viral vectors containing the mVEGF gene (mVEGF:RCAS) was validated in vitro and in vivo, as was the ability of the mVEGF:DF‐1 cells to induce neovascularization in the ex ova CAM model. Using the system, we determined the ability of mVEGF:DF‐1 cells to enhance acetaminophen senor function in vivo, by inducing neovascularization at sites of sensor implantation in the ex ova CAM model. For these studies, acetaminophen sensors were placed on 8‐day‐old ex ova CAMs, followed by addition of media or cells (mVEGF:DF‐1 cells or GFP:DF‐1 cells) at the sites of biosensor implantation on the CAM. At 4 to 10 days after sensor placement, the biosensor function was determined by measuring sensor response to an intravenous injection of acetaminophen. Sensors implanted on CAMs with buffer or control cells (GFP:DF‐1 cells) displayed no induced neovascularization around the sensor and had minimal/baseline sensor responses to intravenous acetaminophen injection (media, 133.33 ± 27.64 nA; GFP:DF‐1, 187.50 ± 55.43 nA). Alternatively, the sensors implanted with mVEGF:DF‐1 cells displayed massive neovascularization and equally massive sensor response to intravenous injection of acetaminophen (VEGF:DF‐1, 1387.50 ± 276.42 nA). These data clearly demonstrate that enhancing vessel density (i.e., neovascularization) around an implanted sensor dramatically enhances sensor function in vivo. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1072–1086, 2003
Activation of calcineurin expression in ischemia‐reperfused rat heart and in human ischemic myocardium
Authors: Lakshmikuttyamma Ashakumary , Selvakumar Ponniah , Kakkar Rakesh , Kanthan Rani , Wang Rui , Sharma Rajendra K. 
Published: November 2003

AbstractCalcineurin (CaN) has been reported as a critical mediator for cardiac hypertrophy and cardiac myocyte apoptosis. In the present study, we investigated the activity and expression of CaN and the effect of calpain in rat heart after ischemia and reperfusion. Rat ischemic heart showed significant increase in CaN activity. Western blot analysis of normal rat heart extract with a polyclonal antibody raised against bovine CaN indicated a prominent immunoreactive band of 60 kDa (CaN A). In ischemic‐reperfused hearts, the expression of CaN A was significantly low and immunoreactivity was observed in proteolytic bands of 46 kDa. This may be due to the proteolytic degradation of CaN A in ischemic tissues by m‐calpain. We also noticed in vitro proteolysis of bovine cardiac CaN A by m‐calpain. Immunohistochemical studies showed strong staining of immunoreactivity in rat hearts that had gone under 30 min ischemia followed by 30 min reperfusion similar to that found in human ischemic heart. Ischemia is associated with multiple alterations in the extracellular and intracellular signaling of cardiomyocytes and may act as an inducer of apoptosis. The increase in CaN activity and strong immunostaining observed in ischemic/perfused rat heart may be due to the calpain‐mediated proteolysis of this phosphatase. © 2003 Wiley‐Liss, Inc.
Bcl‐2 prevents hypoxia/reoxygenation‐induced cell death through suppressed generation of reactive oxygen species and upregulation of Bcl‐2 proteins
Authors: Saitoh Yasukazu , Ouchida Rika , Miwa Nobuhiko 
Published: November 2003

AbstractThe function of bcl‐2 in preventing cell death is well known, but the mechanisms whereby bcl‐2 functions are not well characterized. One mechanism whereby bcl‐2 is thought to function is by alleviating the effects of oxidative stress upon the cell. To examine whether Bcl‐2 can protect cells against oxidative injury resulting from post‐hypoxic reoxygenation (H/R), we subjected rat fibroblasts Rat‐1 and their bcl‐2 transfectants b5 to hypoxia (5% CO2, 95% N2) followed by reoxygenation (5% CO2, 95% air). The bcl‐2 transfectants exhibited the cell viability superior to that of their parent non‐transfectants upon treatment with reoxygenation after 24‐, 48‐, or 72‐h hypoxia, but not upon normoxic serum‐deprivation or upon serum‐supplied hypoxic treatment alone. Thus bcl‐2 transfection can prevent cell death of some types, which occurred during H/R but yet not appreciably until termination of hypoxia. The time‐sequential events of H/R‐induced cell death were shown to be executed via (1) reactive oxygen species (ROS) production at 1–12 h after H/R, (2) activation of caspases‐1 and ‐3, at 1–3 h and 3–6 h after H/R, respectively, and (3) loss of mitochondrial membrane potential (ΔΨ) at 3–12 h after H/R. These cell death‐associated events were prevented entirely except caspase‐1 activation by bcl‐2 transfection, and were preceded by Bcl‐2 upregulation which was executed as early as at 0–1 h after H/R for the bcl‐2 transfectants but not their non‐transfected counterpart cells. Thus upregulation of Bcl‐2 proteins may play a role in prevention of H/R‐induced diminishment of cell viability, but may be executed not yet during hypoxia itself and be actually operated as promptly as ready to go immediately after beginning of H/R, resulting in cytoproteciton through blockage of either ROS generation, caspase‐3 activation, or ΔΨ decline. © 2003 Wiley‐Liss, Inc.