bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitroevaluation of different heat‐treated radio frequency magnetron sputtered calcium phosphate coatings
Authors: Yonggang Yan , Wolke Joop G. C. , Yubao Li , Jansen John A.
Published: February 2007

Objectives:Surface chemical compositions, such as calcium/phosphorus ratio and phase content, have a strong influence on the bioactivity and biocompatibility of calcium phosphate (CaP) coatings as applied on orthopedic and dental implants.

Material and methods:Hydroxylapatite (HA) and dicalcium pyrophosphate (DCPP) coatings were prepared on titanium substrates by RF magnetron sputter deposition. The surfaces were left as‐prepared (amorphous HA coating; A‐HA, amorphous DCPP coating; A‐DCPP) or heat treated with: infrared (IR) at 550°C (I‐HA) or at 650°C (I‐DCPP), and a water steam at 140°C (S‐HA and S‐DCPP). The surface changes of these coatings were determined after incubation in simulated body fluid (SBF). Also, the growth of rat bone marrow cells (RBM) was studied with scanning electron microscopy (SEM).

Results:Both IR and water steam heat treatment changed the sputter‐deposited coatings from the amorphous into the crystalline phase. As‐prepared amorphous coatings dissolved partially in SBF within 4 weeks of incubation, while heat‐treated coatings supported the deposition of a precipitate, i.e., carbonated apatite on both I‐HA and S‐HA specimens, and tricalciumphosphate on the I‐DCPP and S‐DCPP specimens. The Ca/P ratio of the A‐HA, I‐HA, S‐HA, A‐DCPP, I‐DCPP and S‐DCPP coatings changed, respectively, from 1.98 to 1.12, 2.01 to 1.76, 1.91 to 1.68, 0.76 to 1.23, 0.76 to 1.26 and 1.62 to 1.55 after 4 weeks of incubation in SBF. Finally, the RBM cells grew well on all heat‐treated coatings, but showed different mineralization morphology during cell culturing.

Conclusion:The different heat‐treatment procedures for the sputtered HA and DCPP coatings influenced the surface characteristics of these coatings, whereby a combination of crystallinity and specific phase composition (Ca/P ratio) strongly affected theirin vitrobioactivity.
Effect of Bio‐Oss® on osseointegration of dental implants surrounded by circumferential bone defects of different dimensions: an experimental study in the dog
Authors: Polyzois Ioannis , Renvert Stefan , Bosshardt Dieter D. , Lang Niklaus P. , Claffey Noel
Published: February 2007

Objectives: This study was designed to evaluate the effect of gap width and graft placement on bone healing around implants placed in simulated extraction sockets of various widths in four Labrador dogs.

Materials and Methods: Five Osseotite® implants per dog were placed in the mandible of four dogs. Two implants were inserted into sites with a 2.37 mm and two with a 1 mm gap present between the implants and bone around the coronal 6 mm of the implants in each dog. For one of each gap sizes, the gap was filled with Bio‐Oss®, and the other two with blood alone. A fifth implant was inserted without a gap and used as a control. Ground sections were prepared from biopsies taken at 4 months and histometric measurements of osseointegration and bone between the threads made for the coronal 6 mm.

Results: The medians for osseointegration ranged from 5.2 mm for control to 1–2.6 mm for the test modalities. There were significant differences for linear measurements of osseointegration (χ2 18.27; df 4; P=0.0011) and bone area within threads (χ2 23.4; df 4; P=0.0001) between test modalities.

Conclusions: The results suggest that the wider the gap around the implants, the less favourable the histological outcome at short time intervals following treatment. They also infer that bone grafting with anorganic bovine bone xenograft seems to lead to a more favourable histological outcome for wider circumferential defects but not for narrower defects.
Oxidation of resin acids in colophony (rosin) and its implications for patch testing
Authors: Sadhra S. , Foulds I. S , Gray C. N.
Published: February 2007

Commercial preparations of colophony (rosin) used for patch testing are made from unmodified rosin in pet. and may be stored for some considerable time before being used. This would be satisfactory if the composition and dermatological activity of the preparations were both reproducible and stable, but investigations by the authors have shown that the resin acids undergo progressive and substantial oxidation and that the dermatological activity of the preparations increases significantly with time. This may be a cause of inconsistent patch test results unless the composition can be stabilized. Gas liquid chromatography (GLC) analysis of a raw rosin sample and its commercial patch test preparation has shown that they both contained the same resin acids, but the concentration of the abietic type resin acids was found to be lower in the patch test preparations. The degradation of resin acids is due to their atmospheric oxidation, which may occur during the preparation and storage of the commercial rosin patch test preparation. The susceptibility of individual resin acids to atmospheric oxidation was demonstrated by analysing a sample of raw Portuguese gum rosin, which was then left exposed to air and light. Most of the resin acids were found to undergo oxidation at a rate which gradually diminished. More importantly, it is presumed that the concentration of oxidized resin acids increased correspondingly, and these have been shown to be more dermatologically active than the unoxidised resin acids. The rate of decrease of resin acid concentration was found to be in the following order: neoabietic > levopimaric and palustric > abietic > dehydroabetic acid. The pimaric type resin acids were found to be relatively inert to atmospheric oxidation when compared with the abietic type resin acids. Patch testing with the resulting partly oxidized Portuguese rosin produced positive reactions at a 35% higher frequency than the raw Portuguese rosin. The study demonstrates that the allergic potential of unmodified rosin may increase with exposure to air and light. It is therefore recommended that rosin preparations are analysed routinely as part of a quality control programme, which will enable better validation and comparison of patch test results from different dermatological centres. Since the oxidized resin acids are the main allergens in unmodified rosin, it is important that the concentration of the oxidized resin acids is kept high as well as constant in commercial patch test preparations.
Effectiveness of two oral pastes for the treatment of recurrent aphthous stomatitis
Authors: Rodríguez M , Rubio JA , Sanchez R
Published: February 2007

Objective:  To compare the effectiveness of two topical medications to reduce the pain and size of recurrent minor aphthous ulcers.

Setting:  Ten Colombian Dental Faculties’ clinics.

Design:  A double‐blind randomized multi‐centre clinical study.

Subjects:  Ninety‐six patients complaining of at least five acute aphthous ulcers were randomized to two intervention groups. Sample size was calculated using an alpha error of 0.05 and beta of 0.20

Materials and methods:  Participants were randomly assigned to receive 5% amlexanox or a 0.05% clobetasol propionate magistral preparation. Observers at the participating institutions were previously trained to standardize clinical diagnosis and data recollection. Ulcer size and pain were measured on treatment days 0, 2 and 5.

Results:  No significant differences were found between the two groups studied in any of the studied variables at baseline. Both treatment medications significantly reduced pain magnitude and the index ulcer's size on days 2 and 5 compared with day 0 without adverse reactions (within groups differences). No statistical differences between groups of the study medications were found.

Conclusion:  The two treatments applied had similar effectiveness as they both relieved pain and reduced the size of recurrent aphthous ulcers.
Stem cells and the dental pulp: potential roles in dentine regeneration and repair
Authors: Sloan AJ , Smith AJ
Published: February 2007

The dentine–pulp complex displays exquisite regenerative potential in response to injury. The postnatal dental pulp contains a variety of potential progenitor/stem cells, which may participate in dental regeneration. A population of multipotent mesenchymal progenitor cells known as dental pulp stem cells with high proliferative potential for self‐renewal has been described and may be important to the regenerative capacity of the tissue. The nature of the progenitor/stem cell populations in the pulp is of importance in understanding their potentialities and development of isolation or recruitment strategies, and allowing exploitation of their use in regeneration and tissue engineering. Various strategies will be required to ensure not only effective isolation of these cells, but also controlled signalling of their differentiation and regulation of secretory behaviour. Characterization of these cells and determination of their potentialities in terms of specificity of regenerative response will form the foundation for development of new clinical treatment modalities, whether involving directed recruitment of the cells and seeding of stem cells at sites of injury for regeneration or use of the stem cells with appropriate scaffolds for tissue engineering solutions. Such approaches will provide an innovative and novel biologically based new generation of clinical treatments for dental disease.
Molecular genetics of premalignant oral lesions
Authors: Mithani SK , Mydlarz WK , Grumbine FL , Smith IM , Califano JA
Published: February 2007

Oral squamous cell carcinoma (OSCC) is characterized by cellular and subcellular alterations that are associated with a progression towards dedifferentiation and growth. There are several histologically distinct lesions of the oral cavity which have malignant potential. These are leukoplakia, erythroplakia, lichen planus, and submucous fibrosis. These are characterized by a spectrum of chromosomal, genetic, and molecular alterations that they share with each other as well as with the malignant lesions that develop from them. In this review we summarize the investigation of the molecular genetics of each of these lesions and relate them to the alterations, which have been demonstrated in OSCC, to define their location on the continuum of changes, which lead to malignant transformation.
Myogenic precursor cells in craniofacial muscles
Authors: McLoon LK , Thorstenson KM , Solomon A , Lewis MP
Published: February 2007

Craniofacial skeletal muscles (CskM), including the masticatory (MM), extraocular (EOM) and laryngeal muscles (LM), have a number of properties that set them apart from the majority of skeletal muscles (SkM). They have embryological origins that are distinct from musculature elsewhere in the body, they express a number of immature myosin heavy chain isoforms and maintain increased and distinct expression of a number of myogenic growth factors and their receptors from other adult SkMs. Furthermore, it has recently been demonstrated that unlike limb SkM, normal adult EOM and LM retain a population of activated satellite cells, the regenerative cell in adult SkM. In order to maintain this proliferative pool throughout life, CSkM may contain more satellite cells and/or more multipotent precursor cells that may be more resistant to apoptosis than those found in limb muscle. A further exciting question is whether this potentially more active muscle precursor cell population could be utilized not only for SkM repair, but be harnessed for repair or reconstruction of other tissues, such as nervous tissue or bone. This is a highly attractive speculation as the innate regenerative capacity of craniofacial muscles would ensure the donor tissue would not have compromised future function.
Acute upper airway obstruction from acquired angioedema
Authors: Cheng William YC , Smith William B , Russell W John
Published: February 2007

C1 esterase inhibitor deficiency is an unusual cause of acute upper airway angioedema. This case of angioedema is secondary to acquired C1 esterase inhibitor deficiency associated with neoplastic disease and triggered by the use of angiotensin converting enzyme inhibitors. It was sufficiently severe to require emergency airway management. A guide to the evaluation and management of angioedema is presented.
Three-Dimensional Time-Domain Analysis of Very Large Floating Structures Subjected to Unsteady External Loading
Authors: Liuchao Qiu , Hua Liu
Published: February 2007

The strong interest in very large floating structure (VLFS) is a result of a need to utilize effectively the ocean space for transportation, industrial use, storage, habitats, and military bases, among others. The VLFS has great width and length and relatively small flexural rigidity, therefore, investigation of its hydroelastic behavior including fluid-structure interaction is of greater importance than studies of its motion as rigid bodies. In addition to the most important wave-induced responses, the operation of the VLFS also requires determination of its dynamic responses with respect to the effect of unsteady external loading due to intense traffic, load movement, takeoffs and landings of airplanes, missile takeoffs, etc. Therefore, the transient responses of a VLFS to impulsive and moving loads must be studied by a reliable calculation method. In this study, a finite element procedure developed directly in time domain for solution of transient dynamic response of the coupled system consists of a VLFS and a fluid domain subjected to arbitrary time-dependent external loads is presented. The hydrodynamic problem is formulated based on linear, inviscid, and slightly compressible fluid theory and the structural response is analyzed under the thin plate assumption. For numerical calculations, a scaled model of the Mega-Float is exemplified. Three tests—weight pull-up test, weight drop test, and weight moving test which idealize the airplane landing and takeoff—are carried out and compared with published experimental data. The overall agreement was favorable which indicates the validation of the present method.
Developing Innovative Deep Water Pipeline Construction Techniques with Physical Models
Authors: Brown R. J. , Palmer Andrew
Published: February 2007

On the large scale of deep-water construction, marine pipelines are extremely flexible. Construction procedures can exploit that flexibility to connect pipelines and risers to floaters, manifolds, wellheads, buoys, and platforms. The paper describes a three-dimensional physical model technique. It helps the engineer to think imaginatively and rapidly to explore different options, with the objective of minimizing construction risk and creating procedures that can be accomplished by the equipment available. The relevant governing equations are derived, and from them come the conditions required for the model to obey the correct mechanical similarity conditions. The model is exact, and can be used to derive forces and stresses; it is much more than just a picture. The paper describes a series of applications to two- and three-dimensional pipeline construction problems, most recently an application to the current Thunder Horse project.
Numerical Prediction of Impact-Related Wave Loads on Ships
Authors: Schellin Thomas E. , Moctar Ould el
Published: February 2007

We present a numerical procedure to predict impact-related wave-induced (slamming) loads on ships. The procedure was applied to predict slamming loads on two ships that feature a flared bow with a pronounced bulb, hull shapes typical of modern offshore supply vessels. The procedure used a chain of seakeeping codes. First, a linear Green function panel code computed ship responses in unit amplitude regular waves. Ship speed, wave frequency, and wave heading were systematically varied to cover all possible combinations likely to cause slamming. Regular design waves were selected on the basis of maximum magnitudes of relative normal velocity between ship critical areas and wave, averaged over the critical areas. Second, a nonlinear strip theory seakeeping code determined ship motions under design wave conditions, thereby accounting for the nonlinear pressure distribution up to the wave contour and the frequency dependence of the radiation forces (memory effect). Third, these nonlinearly computed ship motions constituted part of the input for a Reynolds-averaged Navier–Stokes equations code that was used to obtain slamming loads. Favorable comparison with available model test data validated the procedure and demonstrated its capability to predict slamming loads suitable for design of ship structures.
Detection of BRAF V600E activating mutation in papillary thyroid carcinoma using PCR with allele-specific fluorescent probe melting curve analysis
Authors: Rowe Leslie R , Bentz Brandon G , Bentz Joel S
Published: February 2007

Background:

A single hotspot mutation at nucleotide 1799 of theBRAFgene has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence of 29–83%.

Aims:

To use a PCR assay to molecularly characterise theBRAFactivating point mutation in a series of PTC and benign thyroid cases and correlate the mutation results with histological findings.

Methods:

Formalin-fixed paraffin-embedded (FFPE) sections were evaluated for theBRAFV600E mutation using LightCycler PCR with allele-specific fluorescent probe melting curve analysis (LCPCR).

Results:

42 (37 PTC; 5 benign) surgical tissue samples were analysed for theBRAFV600E activating point mutation. Using LCPCR and direct DNA sequencing, theBRAFmutation was identified in 23/37 (62.2%) PTC FFPE samples. DNA sequencing results demonstrated confirmation of the mutation.

Conclusions:

Detection of BRAF-activating mutations in PTC suggests new approaches to management and treatment of this disease that may prove worthwhile. Identification of the BRAF V600E activating mutation in routine FFPE pathology samples by a rapid laboratory method such as LCPCR could have significant value.
Periacinar retraction clefting in proliferative prostatic atrophy and prostatic adenocarcinoma
Authors: Ulamec Monika , Tomas Davor , Ensinger Christian , Čupić Hrvoje , Belicza Mladen , Mikuz Gregor , Krušlin Božo
Published: February 2007

Aims:

To evaluate the presence and extent of periacinar retraction clefting in proliferative prostatic atrophy and carcinoma in radical prostatectomy specimens.

Methods:

Atrophic foci and neoplastic glands were analysed in specimens from 50 patients who underwent radical prostatectomy. Analysed atrophic glands were classified in two main groups, proliferative atrophy (PA) and proliferative inflammatory atrophy (PIA); each group was subclassified into simple atrophy (SA) and postatrophic hyperplasia (PAH). According to the presence and extent of periacinar retraction clefting, atrophic and neoplastic glands were classified as: group 1, glands without clefts or with clefts affecting ⩽50% of gland circumference; group 2, glands with clefts that affected >50% of the circumference in <50% of examined glands; and group 3, glands with clefts that affected >50% of the circumference in ⩾50% of examined glands.

Results:

Forty-four (88.0%) atrophic foci were without periacinar clefts or clefts were present in less than half of the gland circumference (group 1). In 6 (12.0%), atrophic foci clefts affected >50% of gland circumference (groups 2 and 3). Forty-five (90.0%) carcinomas were with clefts which affected more than 50% of gland circumference (groups 2 and 3); and in five carcinomas only, clefts were not found or affected <50% of gland circumference (group 1).

Conclusion:

Results indicate that periacinar retraction clefting represents a reliable criterion in differential diagnosis between proliferative atrophy and carcinoma.
Characterization of intestinal phosphate absorption using a novel in vivo method
Authors: Williams Katie Beth , DeLuca Hector F.
Published: February 2007

A new, completely in vivo method of measuring the rate of intestinal phosphate absorption has been developed. As expected from previous in vitro and ex vivo measurements, intestinal phosphate absorption is potently and rapidly stimulated by 1,25-dihydroxyvitamin D3. The response is saturated with as little as 11.3 ng of 1,25-dihydroxyvitamin D3 per day, consistent with a genomic mechanism. The effect of 1,25-dihydroxyvitamin D3 disappears when the dosing solution of phosphate is at 2 M, suggesting that 1,25-dihydroxyvitamin D3 stimulates active transport of phosphate but not diffusion of phosphate. Finally, unlike findings resulting from in vitro or ex vivo experiments, no evidence in vivo was obtained that phosphate absorption requires sodium or is inhibited by potassium.
Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies
Authors: Stellingwerff Trent , Boon Hanneke , Jonkers Richard A. M. , Senden Joan M. , Spriet Lawrence L. , Koopman René , van Loon Luc J. C.
Published: February 2007

Intramyocellular triacylglycerol (IMTG) has been suggested to represent an important substrate source during exercise. In the present study, IMTG utilization during exercise is assessed through the use of various methodologies. In addition, we identified differences in the use of intramyocellular lipids deposited in the immediate subsarcolemmal (SS) area and those stored in the more central region of the fiber. Contemporary stable isotope technology was applied in combination with muscle tissue sampling before and immediately after 3 h of moderate-intensity cycling exercise (62 ± 2% V̇o2 max) in eight well-trained male cyclists. Continuous infusions with [U-13C]palmitate and [6,6-2H2]glucose were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate whole body IMTG and glycogen use. Both immunohistochemical analyses of oil red O (ORO)-stained muscle cross sections and biochemical triacylglycerol (TG) extraction were performed to assess muscle lipid content. During exercise, plasma FFA, muscle (and/or lipoprotein)-derived TG, plasma glucose, and muscle glycogen oxidation contributed 24 ± 2, 22 ± 3, 11 ± 1, and 43 ± 3% to total energy expenditure, respectively. In accordance, a significant net decline in muscle lipid content was observed following exercise as assessed by ORO staining (67 ± 8%) and biochemical TG extraction (49 ± 8%), and a positive correlation was observed between methods ( r = 0.56; P < 0.05). Lipid depots located in the SS area were utilized to a greater extent than the more centrally located depots. This is the first study to show significant use of IMTG as a substrate source during exercise in healthy males via the concurrent implementation of three major methodologies. In addition, this study shows differences in resting subcellular intramyocellular lipid deposit distribution and in the subsequent net use of these deposits during exercise.
Expression of MAK-V/Hunk in renal distal tubules and its possible involvement in proliferative suppression
Authors: Sakai Masashi , Tamura Kouichi , Tsurumi Yuko , Tanaka Yutaka , Koide Yuichi , Matsuda Miyuki , Ishigami Tomoaki , Yabana Machiko , Tokita Yasuo , Hiroi Yukio , Komuro Issei , Umemura Satoshi
Published: February 2007

MAK-V/Hunk is an SNF1-related serine/threonine kinase which was previously shown to be highly expressed in the mammary gland and central nervous system. In this study, we found MAK-V/Hunk is abundantly and specifically expressed in the thick ascending limbs and distal convoluted tubules (DCT) of the kidney from the embryonic stage to the adult stage. We demonstrated that dietary salt depletion significantly enhances renal MAK-V/Hunk mRNA levels compared with a normal-salt diet. To analyze the possible renal cellular function of this kinase, we employed mouse distal convoluted tubule (mDCT) cells. The results of reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that MAK-V/Hunk is expressed endogenously in mDCT cells. Overexpression of MAK-V/Hunk by adenoviral gene transfer significantly inhibited the ANG II-induced stimulation of c- fos gene transcription and suppressed the ANG II-mediated increases in transforming growth factor-β production into the medium. This phenomenon was accompanied by inhibition of ANG II-induced activation of BrdU incorporation. On the other hand, the MAK-V/Hunk knockdown by siRNA activated the ANG II-induced c- fos gene expression. In the consecutive sections stained for MAK-V/Hunk and AT1receptor, MAK-V/Hunk-immunopositive distal tubules expressed the AT1receptor. This is the first report on the intrarenal localization of MAK-V/Hunk and its cellular function in renal tubular cells.
TGF-β-activated kinase 1 and TAK1-binding protein 1 cooperate to mediate TGF-β1-induced MKK3-p38 MAPK activation and stimulation of type I collagen
Authors: Kim Sung Il , Kwak Joon Hyeok , Zachariah Mareena , He Yanjuan , Wang Lin , Choi Mary E.
Published: February 2007

We have previously demonstrated that transforming growth factor-β1(TGF-β1) rapidly activates the mitogen-activated protein kinase kinase 3 (MKK3)-p38 MAPK signaling cascade, leading to the induction of type I collagen synthesis in mouse glomerular mesangial cells (Wang L, Ma R, Flavell RA, Choi ME. J Biol Chem 277: 47257–47262, 2002). In the present study, we investigated the functional role of upstream TGF-β-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1) in the TGF-β1signaling cascade. Rapid activation of endogenous TAK1 activity by TGF-β1was observed in mouse mesangial cells. Transient overexpression of TAK1 with TAB1 enhanced the activation of MKK3 and p38 MAPK with or without TGF-β1stimulation, whereas a dominant-negative mutant of TAK1 (TAK1DN) suppressed TGF-β1-induced activation of MKK3 and p38 MAPK. Moreover, constitutive expression of TAK1DN reduced steady-state protein levels of MKK3 and p38 MAPK as well as MKK3 phosphorylation. Increased p38α MAPK activity by ectopic expression of either TAB1 or wild-type p38α MAPK resulted in enhanced TGF-β1-induced type I collagen expression. In contrast, constitutive expression of TAK1DN inhibited collagen induction. Taken together, our data indicate that TAK1 and TAB1 play a pivotal role as upstream signal transducers activating the MKK3-p38 MAPK signaling cascade that leads to the induction of type I collagen expression by TGF-β1. In addition, our findings also suggest that TAK1 has a novel function in regulation of the steady-state protein levels of MKK3 and p38 MAPK.
A new method for determining plasma water content: application in pseudohyponatremia
Authors: Nguyen Minhtri K. , Ornekian Vahram , Butch Anthony W. , Kurtz Ira
Published: February 2007

Pseudohyponatremia is a clinical condition characterized by an increased fraction of protein or lipid in plasma, thereby resulting in an artificially low plasma sodium concentration ([Na+]p). Since the automated method of measuring [Na+]pin most laboratories involves the use of an indirect ion-selective electrode (I-ISE), this method does not correct for elevated protein or lipid concentrations. In I-ISE, the plasma sample is diluted before the actual measurement is obtained, and the [Na+]pis determined based on the assumption that plasma is normally composed of 93% plasma water. Therefore, the [Na+]pas determined by I-ISE will be artificially low in clinical conditions when the plasma water content (PWC) is <93%. In contrast, the plasma is not diluted when the [Na+]pis measured using direct ISE (D-ISE). This method directly measures Na+activity in plasma water and is therefore unaffected by the proportion of plasma occupied by water. In this study, we report a novel quantitative method for determining the PWC utilizing I-ISE and D-ISE. To validate this new method experimentally, we altered the PWC in vitro by dissolving varying amount of salt-free albumin in human plasma. We then measured PWC gravimetrically in each sample and compared the gravimetrically determined PWC with the ISE-determined PWC. Our findings indicate that the PWC can be accurately determined based on differences in the [Na+]pas measured by I-ISE and D-ISE and that this new quantitative method can be a useful adjunct in the analysis of the dysnatremias.
Blood Levels of Long-Chain Polyunsaturated Fatty Acids, Aspirin, and the Risk of Colorectal Cancer
Authors: Hall Megan N. , Campos Hannia , Li Haojie , Sesso Howard D. , Stampfer Meir J. , Willett Walter C. , Ma Jing
Published: February 2007

Background: N-3 fatty acids may decrease risk of colorectal cancer by inhibiting the cyclooxygenase-2 enzyme and production of proinflammatory eicosanoids derived from arachidonic acid (20:4n-6). Aspirin also inhibits the cyclooxygenase-2 enzyme and may share with n-3 fatty acids a potential mechanism to decrease the risk of colorectal cancer.

Methods: We conducted a nested case-control analysis using blood samples collected from the Physicians' Health Study participants in 1982 to 1984. N-3 and n-6 fatty acid levels were measured using gas-liquid chromatography for 178 men who developed colorectal cancer through December 31, 1995 and 282 age- and smoking-matched controls. We used conditional logistic regression to examine associations. All statistical tests were two-sided.

Results: Total long-chain n-3 fatty acids were nonsignificantly inversely associated with colorectal cancer risk [relative risk (RR) for highest versus lowest quartile, 0.60; 95% confidence interval (95% CI), 0.32 to 1.11; Ptrend = 0.10], after adjustment for possible confounders. We observed potential interaction between randomized aspirin assignment and long-chain n-3 fatty acid levels (Pinteraction = 0.04). Among men not on aspirin, RRs (95% CI) for increasing quartiles of long-chain n-3 fatty acids were 1.00 (reference), 0.60 (0.28-1.28), 0.51 (0.22-1.17), and 0.34 (0.15-0.82), Ptrend = 0.006. For participants taking aspirin, there was no additional benefit of increasing n-3 fatty acid levels. The RR (95% CI) for the highest versus lowest quartile of n-6 fatty acids was 0.64 (0.35-1.17).

Conclusions: Blood levels of long-chain n-3 fatty acids were associated with decreased risk of colorectal cancer among men not using aspirin. N-6 fatty acids were nonsignificantly inversely associated with colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(2):314–21)
In situ Assessment of Intraepithelial Neoplasia in Hamster Trachea Epithelium Using Angle-Resolved Low-Coherence Interferometry
Authors: Chalut Kevin J. , Kresty Laura A. , Pyhtila John W. , Nines Ronald , Baird Maureen , Steele Vernon E. , Wax Adam
Published: February 2007

Optical spectroscopy was used to evaluate the transformation of nuclear morphology associated with intraepithelial neoplasia in an animal model of carcinogenesis. In this pilot study, we have assessed the capability of angle-resolved low-coherence interferometry (a/LCI) to monitor in situ the neoplastic progression of hamster trachea epithelial tissue. By using the depth resolution made possible by coherence gating, the a/LCI system has been adapted to the unique geometry of the hamster trachea to allow us to extract useful nuclear morphometric information from cells in the epithelial layer without the need for exogenous staining or tissue fixation. Analysis of a/LCI nuclear morphology measurements has identified two important biomarkers of neoplastic transformation in hamster trachea epithelium, the size and the refractive index of epithelial cell nuclei. By comparing the a/LCI measurements of these two biomarkers to pathologic classification, we distinguished nuclear morphology changes for normal tissue, low-grade dysplasia, and high-grade dysplasia. Given its previous usefulness for tracking neoplastic change through nuclear morphometry measurements, the a/LCI technique may prove to be a useful tool in evaluating chemopreventive agents in future studies of hamster trachea epithelium. (Cancer Epidemiol Biomarkers Prev 2007;16(2):223–7)
Toll-Like Receptor 4 Genetic Variation and Advanced Prostate Cancer Risk
Authors: Cheng Iona , Plummer Sarah J. , Casey Graham , Witte John S.
Published: February 2007

Toll-like receptor 4 (TLR4) is a key innate immunity receptor that initiates an inflammatory response primarily against Gram-negative bacteria. Two recent publications reported that variants in TLR4 were associated with risk of prostate cancer. To further investigate the role of TLR4 in prostate cancer susceptibility, we identified six tagging single-nucleotide polymorphisms that comprehensively captured the common genetic variation of the locus and tested these polymorphisms in our case-control study of 1,012 men. Two single-nucleotide polymorphisms showed nominally statistically significant associations with prostate cancer risk, with the strongest (rs10759932) associated with a 4-fold increased risk of disease (P = 0.006). We estimated through permutation analysis that a similarly strong result would occur by chance 2.5% of the time. Our findings support previous studies and suggest that inherited differences in TLR4 influence prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(2):352–40)
Retention and Use of Breast Cancer Recurrence Risk Information from Genomic Tests: The Role of Health Literacy
Authors: Lillie Sarah E. , Brewer Noel T. , O'Neill Suzanne C. , Morrill Edward F. , Dees E. Claire , Carey Lisa A. , Rimer Barbara K.
Published: February 2007

Background: New genomic technology now allows physicians to provide women with individualized and highly accurate breast cancer recurrence risk estimates that are a key factor in adjuvant (after surgery) therapy decisions. Because these genomic tests are so new, little is known about how well patients understand the tests and their results.

Method: We interviewed 163 stage I or II breast cancer patients at a routine follow-up appointment. We assessed their health literacy (using the Rapid Estimate of Adult Learning in Medicine) as well as their knowledge of and attitudes towards a genomic test that identifies risk of recurrence in hormone receptor–positive, node–negative breast cancer (the OncoType Dx Recurrence Score).

Results: Women with lower health literacy recalled less of the information provided about the recurrence risk test than women with higher health literacy. Health literacy was not related to the amount of additional information women desired. Women with higher health literacy preferred to have a more active role in decisions about the test.

Implications: Health literacy may affect women's capacity to learn about the new genomic tests as well as their desire for informed participation in their medical care. (Cancer Epidemiol Biomarkers Prev 2007;16(2):249–55)
4-(Methylnitrosamino)-I-(3-Pyridyl)-1-Butanone Enhances the Expression of Apolipoprotein A-I and Clara Cell 17-kDa Protein in the Lung Proteomes of Rats Fed a Corn Oil Diet but not a Fish Oil Diet
Authors: Chang Sung Il , El-Bayoumy Karam , Sinha Indu , Trushin Neil , Stanley Bruce , Pittman Brian , Prokopczyk Bogdan
Published: February 2007

The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent lung carcinogens in rodents. Several epidemiologic studies indicated that the development of lung cancer in smokers is influenced by the type and amount of dietary polyunsaturated fatty acids. A high corn oil diet has been shown to increase lung tumor volume and to decrease tumor latency in rats treated with NNK. In this study, we investigated the effects of dietary polyunsaturated fatty acids in the form of corn oil or fish oil on lung proteomes in F344 rats treated with or without NNK. The fish oil diet contained 17% fish oil and 3% corn oil, and the corn oil diet contained 20% corn oil. Rats were sacrificed after 3 months, and lungs were excised. Whole lung tissue proteins were separated by two-dimensional liquid chromatography, and differentially expressed proteins were identified by trypsin digestion and tandem mass spectrometry. Apolipoprotein A-I and Clara cell 17-kDa protein were overexpressed in the lungs of rats fed corn oil diet, compared with fish oil diet. NNK further enhanced their expression in rats fed corn oil diet; this effect was not observed in animals fed fish oil diet. The results suggest that the elevated levels of apolipoprotein A-I and Clara cell 17-kDa protein may be involved in the development of NNK-induced lung cancer in rats fed a high corn oil diet. Therefore, we propose that both proteins may serve as potential biomarkers in future molecular epidemiologic and clinical chemoprevention intervention studies. (Cancer Epidemiol Biomarkers Prev 2007;16(2):228–35)
Serum Adiponectin Concentrations and Tissue Expression of Adiponectin Receptors Are Reduced in Patients with Prostate Cancer: A Case Control Study
Authors: Michalakis Konstantinos , Williams Catherine J. , Mitsiades Nicholas , Blakeman Jennifer , Balafouta-Tselenis Sofia , Giannopoulos Aris , Mantzoros Christos S.
Published: February 2007

Purpose: Adiponectin, an adipocyte-secreted hormone with insulin-sensitizing effects, has been inversely associated with several hormonally dependent malignancies, including breast, endometrial, and colorectal cancer. Few studies have examined serum adiponectin in relation to prostate cancer, and expression of adiponectin receptors has previously not been assessed in prostate tumors.

Experimental Design: We collected plasma samples and covariate data in the context of a case-control study of 300 Greek men, including 75 prostate cancer cases, 75 patients with benign prostatic hyperplasia (BPH), and 150 healthy controls. Prostate tissue samples were taken from 72 cases and 27 noncases and examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry.

Results: Prostate cancer patients had significantly lower plasma adiponectin concentrations as compared with men with BPH and healthy controls (7.4 ± 5.0 versus 11.5 ± 6.4 and 12.8 ± 8.0 ng/mL, respectively). Men in the top two quartiles of adiponectin had a 71% to 73% reduced risk of prostate cancer as compared with men in the lowest quartile after adjusting for age, body mass index, and additional potential confounders. We found no similar relationship between adiponectin and risk of BPH. Results from immunohistochemistry experiments show weaker expression of adiponectin receptors AdipoR1 and AdipoR2 in cancerous versus healthy prostate tissue.

Conclusions: Higher serum adiponectin is associated with a marked reduction in risk of prostate cancer, but not BPH, independently of other risk factors. Malignant prostate tissue samples have reduced expression of adiponectin receptors as compared with benign prostate tissue. These results support a role for adiponectin in the pathogenesis of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(2):308–13)
Changes in 2-Hydroxyestrone and 16α-Hydroxyestrone Metabolism with Flaxseed Consumption: Modification by COMT and CYP1B1 Genotype
Authors: McCann Susan E. , Wactawski-Wende Jean , Kufel Kari , Olson James , Ovando Bladimir , Kadlubar Susan Nowell , Davis Warren , Carter Lisa , Muti Paola , Shields Peter G. , Freudenheim Jo L.
Published: February 2007

Consumption of the phytoestrogen lignans, structurally similar to estrogen, has been associated with alterations in gene expression and estrogen metabolism. Furthermore, lignan consumption, subsequent changes in metabolizing enzyme expression, and genetic variability in these enzymes may alter estrogen metabolism and modify disease risk. Therefore, we investigated the effect of flaxseed on hydroxyestrone metabolite excretion by catechol-O-methyltransferase (COMT) and cytochrome P450 1B1 (CYP1B1) genotype. We conducted an intervention among 132 healthy, postmenopausal women, ages 46 to 75 years. Participants consumed 10 g ground flaxseed daily for 7 consecutive days. Blood and urine samples were collected at baseline and after the 7-day intervention. COMT Val158Met and CYP1B1 Leu432Val genotypes were determined using PCR-RFLP methods. Urinary 2-hydroxyestrone (2OHE1) and 16α-hydroxyestrone (16OHE1) were quantified by ELISA assay. The effect of genotype on intervention-related changes in estrogen metabolites was assessed with the Kruskal-Wallis test. Compared with baseline levels, postintervention levels of urinary 2OHE1 (ng/mg creatinine; mean ± SD, 16.1 ± 10.6 versus 9.3 ± 6.9, postintervention and baseline, respectively; P < 0.01) and 2OHE1/16OHE1 ratios (mean ± SD, 2.73 ± 1.47 versus 1.54 ± 0.75, postintervention and baseline, respectively; P < 0.01) were significantly higher. The change in 2OHE1/16OHE1 increased with increasing numbers of variant alleles for COMT (mean change: Val/Val, 0.90; Val/Met, 1.15; and Met/Met, 1.50; P = 0.17, Kruskal-Wallis) and especially CYP1B1 (mean change: Leu/Leu, 0.89; Leu/Val, 1.32; and Val/Val, 1.51; P = 0.04, Kruskal-Wallis). Our findings suggest that variation in hormone-related genes may modify the effect of dietary lignan exposures on estrogen metabolism. (Cancer Epidemiol Biomarkers Prev 2007;16(2):256–62)
Genetic Variation in the Premature Aging Gene WRN: A Case-Control Study on Breast Cancer Susceptibility
Authors: Ding Shian-ling , Yu Jyh-Cherng , Chen Shou-Tung , Hsu Giu-Cheng , Shen Chen-Yang
Published: February 2007

The high risk of developing cancer seen in human genetic diseases that resemble accelerated aging provides support for a tumorigenic contribution of the mechanisms and genes responsible for regulating life span and aging. We therefore speculated that the WRN gene (encoding RECQL2, a DNA helicase), the germline mutation of which causes the progeroid disorder Werner syndrome, may be associated with breast tumorigenesis. This hypothesis was tested in this case-control study of 935 primary breast cancer patients and 1,545 healthy controls by examining single-nucleotide polymorphisms (SNPs) in WRN. We were also interested in knowing whether any identified association between WRN and breast cancer was modified by reproductive risk factors reflecting susceptibility to estrogen exposure. Our hypothesis is that because estrogen is known to promote breast cancer development via its mitogenic effect leading to cell proliferation, and because WRN is an essential gene, as its suboptimal function leads to a severe decrease in proliferation, estrogen stimulation may have a protective effect on cells harboring variant WRN, allowing them to survive and proliferate for the prolonged period needed for tumor formation. Support for this hypothesis came from the following observations: (a) one SNP in WRN was significantly associated with breast cancer risk (P = 0.002); (b) haplotype and diplotype analyses, based on different combinations of multiple SNPs in WRN, revealed a strong association with breast cancer risk; (c) this association between risk and putative high-risk genotypes was stronger and more significant in women with a longer interval between menarche and first full-term pregnancy; and (d) the protective effect conferred by having a higher number of full-term pregnancy was only significant in women with homozygous or heterozygous wild-type WRN genotypes. This study provides support for the tumorigenic role of WRN in breast cancer development, suggesting that breast cancer can be driven by the aging associated with variant WRN, the tumorigenic contribution of which might be enhanced as a result of increased cell growth due to estrogen exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(2):263–9)
Interaction of Factors Related to the Metabolic Syndrome and Vitamin D on Risk of Prostate Cancer
Authors: Tuohimaa Pentti , Tenkanen Leena , Syvälä Heimo , Lumme Sonja , Hakulinen Timo , Dillner Joakim , Hakama Matti
Published: February 2007

Background: Factors related to the metabolic syndrome and low levels of vitamin D have been implicated as risk factors for prostate cancer. Insofar, no studies have assessed their joint effects on prostate cancer risk.

Methods: We studied (a) the associations of vitamin D with the metabolic syndrome factors body mass index, systolic and diastolic blood pressure, and high-density lipoprotein cholesterol (HDL-C) and (b) the prostate cancer risk associated with these factors and especially their joint effects with vitamin D on risk of prostate cancer. We did a longitudinal nested case-control study on 132 prostate cancer cases and 456 matched controls from a cohort of 18,939 Finnish middle-aged men from the Helsinki Heart Study. The odds ratios (OR) of prostate cancer were assessed via conditional logistic regression analysis.

Results: Apart from HDL-C, there was no linear association between the metabolic syndrome factors and vitamin D levels. In univariate analysis, men in the highest quartiles of body mass index (>28 kg/m2) and systolic blood pressure (>150 mmHg) showed a modest increase in risks of prostate cancer, with ORs of 1.37 (P = 0.16) and 1.53 (P = 0.05) when compared with the three lower quartiles, but low HDL-C entailed no prostate cancer risk. However, with all three factors present, the OR was 3.36 (P = 0.02), and jointly with low vitamin D (≤40 nmol/L), the OR was 8.03 (P = 0.005) compared with those with no metabolic syndrome factors and intermediate levels of vitamin D. There was an interaction between vitamin D and the metabolic syndrome factors so that a clustering of these factors entailed high risk of prostate cancer but only if vitamin D level was low (≤40 nmol/L). If it was at intermediate levels, the metabolic syndrome factors entailed no prostate cancer risk.

Conclusions: We conclude that the prostate cancer risk associated with factors related to the metabolic syndrome is strongly conditioned by levels of vitamin D. (Cancer Epidemiol Biomarkers Prev 2007;16(2):302–7)
Role of Subcellular Remodeling in Cardiac Dysfunction due to Congestive Heart Failure
Authors: Babick Andrea P. , Dhalla Naranjan S.
Published: February 2007

Although alterations in the size and shape of the heart (cardiac remodeling) are considered in explaining cardiac dysfunction during the development of congestive heart failure (CHF), there are several conditions including initial stages of cardiac hypertrophy, where cardiac remodeling has also been found to be associated with either an increased or no change in heart function. Extensive studies have indicated that cardiac dysfunction is related to defects in one or more subcellular organelles such as myofibrils, sarcoplasmic reticulum and sarcolemma, depending upon the stage of CHF. Such subcellular abnormalities in the failing hearts have been shown to occur at both genetic and protein levels. Blockade of the renin-angiotensin system has been reported to partially attenuate changes in subcellular protein, gene expression, functional activities and cardiac performance in CHF. These observations provide support for the role of subcellular remodeling (alterations in molecular and biochemical composition of subcellular organelles) in cardiac dysfunction in the failing heart. On the basis of existing knowledge, it appears that subcellular remodeling during the process of cardiac remodeling plays a major role in the development of cardiac dysfunction in CHF.