bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation during experimental cholestatic ductal hyperplasia
Authors: Moritoki Yuki , Ueno Yoshiyuki , Kanno Noriatsu , Yamagiwa Yoko , Fukushima Koji , Gershwin M. Eric , Shimosegawa Tooru
Published: April 2006

Abstract: Background: Ductopenia is observed in end‐stage human cholestatic diseases. The limited capability of cholangiocytes for proliferation is suggested to be the principal reason. Recently, bone marrow cells (BMCs) have been reported to behave as hepatic stem cells; however, their capability to differentiate into cholangiocytes in cholestasis remains unclear.

Methods: Normal mice were lethally irradiated to suppress the proliferation of self‐BMCs; thereafter, the BMCs from enhanced green fluorescent protein (EGFP)‐transgenic mice were transferred to recipients. Chronic cholestasis was induced by 0.1%α‐naphtylisothiocyanate (ANIT) feeding. The proliferation of cholangiocytes and oval cells was assessed morphologically and immunohistchemically (cytokeratin‐7 (CK‐7), A6). Proliferative activity (proliferating cell nuclear antigen (PCNA) protein expression), hepatic growth factor (HGF) receptor (c‐Met), stem cell factor receptor (c‐kit), Notch2 and Hes1 expression were also evaluated.

Results: Marked cholangiocyte proliferation was observed in ANIT‐fed mice. However, no EGFP/CK‐7 double positive cells were identified in any of the liver specimens after BMCs transfer (Tx). In hepatic parenchyma, there were scattered EGFP‐positive cells, although none of them were positive for CK‐7.

Conclusions: In spite of the significant ductular proliferations after ANIT feeding, no EGFP‐positive cholangiocytes were confirmed by any other means in this chronic cholestasis model. Thus, different from hepatocytes, BMCs Tx seems not to contribute to the differentiation of cholangiocytes. Future studies are feasible to clarify the origin of proliferative cholangiocytes observed in this chronic cholestatic ductular hyperplasia model.
Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration
Authors: Huang Wendong , Ma Ke , Zhang Jun , Qatanani Mohammed , Cuvillier James , Liu Jun , Dong Bingning , Huang Xiongfei , Moore David D.
Published: April 2006

Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor–dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.
CTCF Mediates Interchromosomal Colocalization Between
Igf2/H19
and
Wsb1/Nf1
Authors: Ling Jian Qun , Li Tao , Hu Ji Fan , Vu Thanh H. , Chen Hui Ling , Qiu Xin Wen , Cherry Athena M. , Hoffman Andrew R.
Published: April 2006

Gene transcription may be regulated by remote enhancer or insulator regions through chromosome looping. Using a modification of chromosome conformation capture (3C) and fluorescence in situ hybridization, we found that one allele of the insulin-like growth factor 2 (
Igf2
)/
H19
imprinting control region (ICR) on chromosome 7 colocalized with one allele of
Wsb1/Nf1
on chromosome 11. Omission of CCCTC-binding factor (CTCF) or deletion of the maternal ICR abrogated this association and altered
Wsb1/Nf1
gene expression. These findings demonstrate that CTCF mediates an interchromosomal association, perhaps by directing distant DNA segments to a common transcription factory, and the data provide a model for long-range allele-specific associations between gene regions on different chromosomes that suggest a framework for DNA recombination and RNA trans-splicing.
Comment on "The Illusion of Invariant Quantities in Life Histories"
Authors: Savage Van M. , White Ethan P. , Moses Melanie E. , Ernest S. K. Morgan , Enquist Brian J. , Charnov Eric L.
Published: April 2006

Nee
et al
. (Reports, 19 August 2005, p. 1236) used a null model to argue that life history invariants are illusions. We show that their results are largely inconsequential for life history theory because the authors confound two definitions of invariance, and rigorous analysis of their null model demonstrates that it does not match observed data.
Catalytic Alkane Metathesis by Tandem Alkane Dehydrogenation-Olefin Metathesis
Authors: Goldman Alan S. , Roy Amy H. , Huang Zheng , Ahuja Ritu , Schinski William , Brookhart Maurice
Published: April 2006

With petroleum supplies dwindling, there is increasing interest in selective methods for transforming other carbon feedstocks into hydrocarbons suitable for transportation fuel. We report the development of highly productive, well-defined, tandem catalytic systems for the metathesis of
n
-alkanes. Each system comprises one molecular catalyst (a “pincer”-ligated iridium complex) that effects alkane dehydrogenation and olefin hydrogenation, plus a second catalyst (molecular or solid-phase) for olefin metathesis. The systems all show complete selectivity for linear (
n
-alkane) product. We report one example that achieves selectivity with respect to the distribution of product molecular weights, in which
n
-decane is the predominant high-molecular-weight product of the metathesis of two moles of
n
-hexane.
Hardening by Annealing and Softening by Deformation in Nanostructured Metals
Authors: Huang Xiaoxu , Hansen Niels , Tsuji Nobuhiro
Published: April 2006

We observe that a nanostructured metal can be hardened by annealing and softened when subsequently deformed, which is in contrast to the typical behavior of a metal. Microstructural investigation points to an effect of the structural scale on fundamental mechanisms of dislocation-dislocation and dislocation-interface reactions, such that heat treatment reduces the generation and interaction of dislocations, leading to an increase in strength and a reduction in ductility. A subsequent deformation step may restore the dislocation structure and facilitate the yielding process when the metal is stressed. As a consequence, the strength decreases and the ductility increases. These observations suggest that for materials such as the nanostructured aluminum studied here, deformation should be used as an optimizing procedure instead of annealing.
The Fluorescent Toolbox for Assessing Protein Location and Function
Authors: Giepmans Ben N. G. , Adams Stephen R. , Ellisman Mark H. , Tsien Roger Y.
Published: April 2006

Advances in molecular biology, organic chemistry, and materials science have recently created several new classes of fluorescent probes for imaging in cell biology. Here we review the characteristic benefits and limitations of fluorescent probes to study proteins. The focus is on protein detection in live versus fixed cells: determination of protein expression, localization, activity state, and the possibility for combination of fluorescent light microscopy with electron microscopy. Small organic fluorescent dyes, nanocrystals (“quantum dots”), autofluorescent proteins, small genetic encoded tags that can be complexed with fluorochromes, and combinations of these probes are highlighted.
A Common Genetic Variant Is Associated with Adult and Childhood Obesity
Authors: Herbert Alan , Gerry Norman P. , McQueen Matthew B. , Heid Iris M. , Pfeufer Arne , Illig Thomas , Wichmann H.-Erich , Meitinger Thomas , Hunter David , Hu Frank B. , Colditz Graham , Hinney Anke , Hebebrand Johannes , Koberwitz Kerstin , Zhu Xiaofeng , Cooper Richard , Ardlie Kristin , Lyon Helen , Hirschhorn Joel N. , Laird Nan M. , Lenburg Marc E. , Lange Christoph , Christman Michael F.
Published: April 2006

Obesity is a heritable trait and a risk factor for many common diseases such as type 2 diabetes, heart disease, and hypertension. We used a dense whole-genome scan of DNA samples from the Framingham Heart Study participants to identify a common genetic variant near the
INSIG2
gene associated with obesity. We have replicated the finding in four separate samples composed of individuals of Western European ancestry, African Americans, and children. The obesity-predisposing genotype is present in 10% of individuals. Our study suggests that common genetic polymorphisms are important determinants of obesity.
Considering Multiple Flavors
Authors: Enderby John E.
Published: April 2006

The Access Principle
. The Case for Open Access to Research and Scholarship.
By John WIllinsky
. MIT Press, Cambridge, MA, 2005. 307 pp. $34.95, £22.95. ISBN 0-262-23242-1. Digital Libraries and Electronic Publishing.

The author marshals the arguments for open-access approaches to scientific and academic publishing.
Double Perovskites as Anode Materials for Solid-Oxide Fuel Cells
Authors: Huang Yun-Hui , Dass Ronald I. , Xing Zheng-Liang , Goodenough John B.
Published: April 2006

Extensive efforts to develop a solid-oxide fuel cell for transportation, the bottoming cycle of a power plant, and distributed generation of electric energy are motivated by a need for greater fuel efficiency and reduced air pollution. Barriers to the introduction of hydrogen as the fuel have stimulated interest in developing an anode material that can be used with natural gas under operating temperatures 650°C <
T
< 1000°C. Here we report identification of the double perovskites Sr
2
Mg

1-
x

Mn

x

MoO
6-δ
that meet the requirements for long-term stability with tolerance to sulfur and show a superior single-cell performance in hydrogen and methane.
Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling
Authors: Masgrau Laura , Roujeinikova Anna , Johannissen Linus O. , Hothi Parvinder , Basran Jaswir , Ranaghan Kara E. , Mulholland Adrian J. , Sutcliffe Michael J. , Scrutton Nigel S. , Leys David
Published: April 2006

We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp
128
β in a reaction dominated by tunneling over ∼0.6 angstroms. The role of long-range coupled motions in promoting tunneling is controversial. We show that, in this enzyme system, tunneling is promoted by a short-range motion modulating proton-acceptor distance and no long-range coupled motion is required.
Pathogenic Potential of Novel Chlamydiae and Diagnostic Approaches to Infections Due to These Obligate Intracellular Bacteria
Authors: Corsaro Daniele , Greub Gilbert
Published: April 2006

Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology.
Laboratory Diagnostics of Botulism
Authors: Lindström Miia , Korkeala Hannu
Published: April 2006

Botulism is a potentially lethal paralytic disease caused by botulinum neurotoxin. Human pathogenic neurotoxins of types A, B, E, and F are produced by a diverse group of anaerobic spore-forming bacteria, including Clostridium botulinum groups I and II, Clostridium butyricum, and Clostridium baratii. The routine laboratory diagnostics of botulism is based on the detection of botulinum neurotoxin in the patient. Detection of toxin-producing clostridia in the patient and/or the vehicle confirms the diagnosis. The neurotoxin detection is based on the mouse lethality assay. Sensitive and rapid in vitro assays have been developed, but they have not yet been appropriately validated on clinical and food matrices. Culture methods for C. botulinum are poorly developed, and efficient isolation and identification tools are lacking. Molecular techniques targeted to the neurotoxin genes are ideal for the detection and identification of C. botulinum, but they do not detect biologically active neurotoxin and should not be used alone. Apart from rapid diagnosis, the laboratory diagnostics of botulism should aim at increasing our understanding of the epidemiology and prevention of the disease. Therefore, the toxin-producing organisms should be routinely isolated from the patient and the vehicle. The physiological group and genetic traits of the isolates should be determined.
Navicular stress fractures: outcomes of surgical and conservative management
Authors: Potter N J , Brukner P D , Makdissi M , Crossley K , Kiss Z S
Published: April 2006

Objective:To compare the long term outcomes of the two treatment options for navicular stress fractures: non-weightbearing cast immobilisation and surgical fixation.

Design:Retrospective case study.

Participants:Subjects aged 18 years and older who had been treated for a navicular stress fracture more than two years previously.

Main outcome measures:Questionnaire based analogue pain score and function score; tenderness on palpation; abnormality detected on computed tomography (CT).

Results:In all, 32 fractures in 26 subjects were investigated. No significant differences were found between surgical and conservative management for current pain (p = 0.984), current function (p = 0.170), or abnormality on CT (p = 0.173). However, surgically treated patients more often remained tender over the “N spot” (p = 0.005), even after returning to competition for two years or more.

Conclusions:Surgical fixation of navicular stress fractures appears to be as effective as conservative management over the longer term. However, there remains a small but measurable degree of pain and loss of function over this period. The value of using “N spot” tenderness as the sole clinical predictor of treatment success requires further investigation, as some patients remained tender despite successful completion of treatment and return to competition.
Cryotherapy for acute ankle sprains: a randomised controlled study of two different icing protocols
Authors: Bleakley C M , McDonough S M , MacAuley D C
Published: April 2006

Background:The use of cryotherapy in the management of acute soft tissue injury is largely based on anecdotal evidence. Preliminary evidence suggests that intermittent cryotherapy applications are most effective at reducing tissue temperature to optimal therapeutic levels. However, its efficacy in treating injured human subjects is not yet known.

Objective:: To compare the efficacy of an intermittent cryotherapy treatment protocol with a standard cryotherapy treatment protocol in the management of acute ankle sprains.

Subjects:Sportsmen (n  =  44) and members of the general public (n  =  45) with mild/moderate acute ankle sprains.

Methods:Subjects were randomly allocated, under strictly controlled double blind conditions, to one of two treatment groups: standard ice application (n  =  46) or intermittent ice application (n  =  43). The mode of cryotherapy was standardised across groups and consisted of melting iced water (0°C) in a standardised pack. Function, pain, and swelling were recorded at baseline and one, two, three, four, and six weeks after injury.

Results:Subjects treated with the intermittent protocol had significantly (p<0.05) less ankle pain on activity than those using a standard 20 minute protocol; however, one week after ankle injury, there were no significant differences between groups in terms of function, swelling, or pain at rest.

Conclusion:Intermittent applications may enhance the therapeutic effect of ice in pain relief after acute soft tissue injury.
ON MEASURING IMPRECISION IN HUMAN RESPONSE DUE TO RESPONDENT AND ATTRIBUTE AND ITS UTILITY IN QUESTIONNAIRE DESIGN
Authors: DAS SHUBHABRATA
Published: April 2006

Human Response to a question with multiple alternatives can be imprecise or fuzzy for various reasons. Part of this fuzziness can be attributed to the lack of sincerity and clarity in the thought process of the respondent. A formal measure of this aspect of fuzziness is formulated in this work on the basis of consistency of the respondent's response to the same question repeated in multiple scales. Discarding haphazard and insincere respondents can improve the quality of data resulting in more efficient survey analysis. This may be achieved in the framework of statistical testing of hypothesis using the probability distribution of the proposed fuzziness measure. Similarly, an attribute can be fuzzy, and it may generate inconsistent response from many respondents. The application of the proposed methodology extends to identifying such fuzzy or unclear attributes. The paper also proposes an algorithm for screening inconsistent respondents and fuzzy attributes simultaneously.
EXTENSIONS OF PARTIAL LATTICE-VALUED POSSIBILISTIC MEASURES FROM NESTED DOMAINS
Authors: KRAMOSIL IVAN
Published: April 2006

We investigate a partial non-numerical possibilistic measure taking its values in a complete lattice and defined on a nested system of subsets of the universe under consideration. Our aim is to extend this measure conservatively to the power-set of all systems of this universe using the same idea as that when introducing outer measures. Hence, we ascribe to each subset of the universe its minimal (in the sense of set inclusion) covering by a set from the nested domain and define its possibility degree as identical with the value ascribed to this covering. Also analyzed is the case when they are two lattice-valued possibilistic measures on the same universe, each with its own nested domain and our aim is to define one possibilistic measure on the power-set in question in a way sophistically taking profit of the information offered by both the particular partial lattice-valued measures.
THREE-PARAMETER FUZZY ARITHMETIC APPROXIMATION OF L-R FUZZY NUMBERS FOR FUZZY NEURAL NETWORKS
Authors: WANG HSIAO-FAN , KUO CHING-YI
Published: April 2006

In this study, we proposed an alternative operation of fuzzy arithmetic on L-R fuzzy numbers by three parameters of mode, left spread and right spread. Then, based on this approximation method, a new learning algorithm of a fully fuzzified neural network was developed in which the L-R fuzzy numbers were considered as the fuzzy signals. While the forward operations of fuzzy signals were based on the proposed three-parameter fuzzy arithmetic approximation method, the backward learning adopted a back-propagation learning procedure with a measurable error function. The learning algorithm was illustrated by an example of the recognition of fuzzy IF-THEN rules. The simulation result showed that the proposed approximation method used in such learning model was efficient and accurate.
COMPLETING FUZZY IF-THEN RULE BASES BY MEANS OF SMOOTHING SPLINES
Authors: VETTERLEIN THOMAS , ŠTEPNICKA MARTIN
Published: April 2006

A fuzzy if-then rule base may be viewed as a partial function between universes of fuzzy sets. For the construction of a fuzzy inference module, this partial function needs to be extended to a total one.

Here, we propose a new method how to do so, making use of the method of smoothing splines. To this end, we identify the fuzzy sets with elements of a finite-dimensional real parameter space in an approximate way, using Perfilieva's fuzzy transforms. We then determine a function between two such parameter spaces by requiring that it reproduces the rule base as precise as possible and that it minimizes a parameter depending on its smoothness.
Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis
Authors: LaBerge Jennifer , Malley Susan E. , Zvarova Katarina , Vizzard Margaret A.
Published: April 2006

Corticotropin-releasing factor (CRF) is a prominent neuropeptide involved in micturition reflexes, and different roles in these reflexes have been suggested. These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF receptors, CRF1 and CRF2, was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly ( P ≤ 0.01) increased with 48 h or chronic CYP treatment. CRF immunoreactivity (IR) was increased significantly ( P ≤ 0.01) in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in density in the suburothelial plexus and detrusor smooth muscle whole mounts with CYP-induced cystitis. CRF2 receptor transcript was expressed in the urothelium or detrusor smooth muscle, and CRF2 receptor expression increased in whole bladder with CYP-treatment, whereas no CRF1 receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF2 IR in urinary bladder nerve fibers and urothelial cells from control animals, whereas no CRF1 IR was observed. These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF2) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis.
In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges
Authors: Kellogg D. L.
Published: April 2006

This review focuses on the neural and local mechanisms that have been demonstrated to effect cutaneous vasodilation and vasoconstriction in response to heat and cold stress in vivo in humans. First, our present understanding of the mechanisms by which sympathetic cholinergic nerves mediate cutaneous active vasodilation during reflex responses to whole body heating is discussed. These mechanisms include roles for cotransmission as well as nitric oxide (NO). Next, the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active vasoconstriction during whole body cooling are reviewed, including cotransmission by neuropeptide Y (NPY) acting through NPY Y1 receptors. Subsequently, current concepts for the mechanisms that effect local cutaneous vascular responses to direct skin warming are examined. These mechanisms include the roles of temperature-sensitive afferent neurons as well as NO in causing vasodilation during local heating of skin. This section is followed by a review of the mechanisms that cause local cutaneous vasoconstriction in response to direct cooling of the skin, including the dependence of these responses on intact sensory and sympathetic, noradrenergic innervation as well as roles for nonneural mechanisms. Finally, unresolved issues that warrant further research on mechanisms that control cutaneous vascular responses to heating and cooling are discussed.
Shivering in the cold: from mechanisms of fuel selection to survival
Authors: Haman François
Published: April 2006

In cold-exposed adult humans, significant or lethal decreases in body temperature are delayed by reducing heat loss via peripheral vasoconstriction and by increasing rates of heat production via shivering thermogenesis. This brief review focuses on the mechanisms of fuel selection responsible for sustaining long-term shivering thermogenesis. It provides evidence to explain large discrepancies in fuel selection measurements among shivering studies, and it proposes links between choices in fuel selection mechanism and human survival in the cold. Over the last decades, a number of studies have quantified the contributions of carbohydrate (CHO) and lipid to total heat generation. However, the exact contributions of these fuels still remain unclear because of large differences in fuel selection measurements even at the same metabolic rate. Recent advances on the mechanisms of fuel selection during shivering provide some plausible explanations for these discrepancies between shivering studies. This new evidence indicates that muscles can sustain shivering over several hours using a variety of fuel mixtures achieved by modifying diet (changing the size of CHO reserves) or by changing muscle fiber recruitment (increasing or decreasing the recruitment of type II fibers). From a practical perspective, how does the choice of fuel selection mechanism affect human survival in the cold? Based on a glycogen-depletion model, estimates of shivering endurance show that, whereas the oxidation of widely different fuel mixtures does not improve survival time, the selective recruitment of fuel-specific muscle fibers provides a substantial advantage for cold survival. By combining fundamental research on fuel metabolism and applied strategies to improve shivering endurance, future research in this area promises to yield important new information on what limits human survival in the cold.
Neural control and mechanisms of eccrine sweating during heat stress and exercise
Authors: Shibasaki Manabu , Wilson Thad E. , Crandall Craig G.
Published: April 2006

In humans, evaporative heat loss from eccrine sweat glands is critical for thermoregulation during exercise and/or exposure to hot environmental conditions, particularly when environmental temperature is greater than skin temperature. Since the time of the ancient Greeks, the significance of sweating has been recognized, whereas our understanding of the mechanisms and controllers of sweating has largely developed during the past century. This review initially focuses on the basic mechanisms of eccrine sweat secretion during heat stress and/or exercise along with a review of the primary controllers of thermoregulatory sweating (i.e., internal and skin temperatures). This is followed by a review of key nonthermal factors associated with prolonged heat stress and exercise that have been proposed to modulate the sweating response. Finally, mechanisms pertaining to the effects of heat acclimation and microgravity exposure are presented.
Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults
Authors: Kosek David J. , Kim Jeong-su , Petrella John K. , Cross James M. , Bamman Marcas M.
Published: April 2006

Resistance training (RT) has shown the most promise in reducing/reversing effects of sarcopenia, although the optimum regime specific for older adults remains unclear. We hypothesized myofiber hypertrophy resulting from frequent (3 days/wk, 16 wk) RT would be impaired in older (O; 60–75 yr; 12 women, 13 men), sarcopenic adults compared with young (Y; 20–35 yr; 11 women, 13 men) due to slowed repair/regeneration processes. Myofiber-type distribution and cross-sectional area (CSA) were determined at 0 and 16 wk. Transcript and protein levels of myogenic regulatory factors (MRFs) were assessed as markers of regeneration at 0 and 24 h postexercise, and after 16 wk. Only Y increased type I CSA 18% ( P < 0.001). O showed smaller type IIa (−16%) and type IIx (−24%) myofibers before training ( P < 0.05), with differences most notable in women. Both age groups increased type IIa (O, 16%; Y, 25%) and mean type II (O, 23%; Y, 32%) size ( P < 0.05). Growth was generally most favorable in young men. Percent change scores on fiber size revealed an age × gender interaction for type I fibers ( P < 0.05) as growth among Y (25%) exceeded that of O (4%) men. Myogenin and myogenic differentiation factor D (MyoD) mRNAs increased ( P < 0.05) in Y and O, whereas myogenic factor (myf)-5 mRNA increased in Y only ( P < 0.05). Myf-6 protein increased ( P < 0.05) in both Y and O. The results generally support our hypothesis as 3 days/wk training led to more robust hypertrophy in Y vs. O, particularly among men. However, this differential hypertrophy adaptation was not explained by age variation in MRF expression.
The Heritability of Mammographically Dense and Nondense Breast Tissue
Authors: Stone Jennifer , Dite Gillian S. , Gunasekara Anoma , English Dallas R. , McCredie Margaret R.E , Giles Graham G. , Cawson Jennifer N. , Hegele Robert A. , Chiarelli Anna M. , Yaffe Martin J. , Boyd Norman F. , Hopper John L.
Published: April 2006

Background: Percent mammographic density (PMD) is a risk factor for breast cancer. Our previous twin study showed that the heritability of PMD was 63%. This study determined the heritabilities of the components of PMD, the areas of dense and nondense tissue in the mammogram.

Methods: We combined two twin studies comprising 571 monozygous and 380 dizygous twin pairs recruited from Australia and North America. Dense and nondense areas were measured using a computer-assisted method, and information about potential determinants was obtained by questionnaire. Under the assumptions of the classic twin model, we estimated the heritability of the log dense area and log nondense area and the genetic and environmental contributions to the covariance between the two traits, using maximum likelihood theory and the statistical package FISHER.

Results: After adjusting for measured determinants, for each of the log dense area and the log nondense area, the monozygous correlations were greater than the dizygous correlations. Heritability was estimated to be 65% (95% confidence interval, 60-70%) for dense area and 66% (95% confidence interval, 61-71%) for nondense area. The correlations (SE) between the two adjusted traits were −0.35 (0.023) in the same individual, −0.26 (0.026) across monozygous pairs, and −0.14 (0.034) across dizygous pairs.

Conclusion: Genetic factors may play a large role in explaining variation in the mammographic areas of both dense and nondense tissue. About two thirds of the negative correlation between dense and nondense area is explained by the same genetic factors influencing both traits, but in opposite directions. (Cancer Epidemiol Biomarkers Prev 2006;15(4):612–7)
The Impact of Acculturation on Awareness of Genetic Testing for Increased Cancer Risk among Hispanics in the Year 2000 National Health Interview Survey
Authors: Vadaparampil Susan T. , Wideroff Louise , Breen Nancy , Trapido Edward
Published: April 2006

Previous studies suggest disparities in use of preventive cancer services among U.S. Hispanics are partly explained by knowledge and access factors. One area of emerging interest is uptake of genetic counseling and testing services by underserved populations. This study aims to estimate the percentage of Hispanics in five ethnic subgroups who are aware of genetic testing for inherited cancer risk, and to assess the influence of acculturation factors primarily related to language on test awareness. Weighted data from 4,313 Hispanic respondents (age >25 years) in the year 2000 National Health Interview Survey were analyzed. Overall, 20.6% of Hispanics had heard of genetic testing for cancer risk, with percentages highest among Puerto Ricans (27.3%) and lowest among Mexicans (14.3%). Completing the interview in Spanish and English [odds ratio (OR), 0.52; 95% confidence interval (95% CI), 0.35-0.78], or only Spanish (OR, 0.60; 95% CI, 0.42-0.86), was inversely associated with test awareness (reference group, only English). Having an intermediate (OR, 0.66; 95% CI, 0.48-0.90) or low (OR, 0.63; 95% CI, 0.39-1.01) level of English language preference was also inversely associated (reference, high level) whereas being born outside the United States was weakly associated (OR, 0.80; 95% CI, 0.57-1.11). Estimates were adjusted for age, education, ethnicity, parents' cancer history, health care access, and selected health behaviors and beliefs. Results of this national survey indicate that acculturation factors related to language may affect cancer genetic test awareness in Hispanics. These factors must be taken into account when informing individuals about the role of genetics in cancer risk and providing cancer genetic health services. (Cancer Epidemiol Biomarkers Prev 2006;15(4):618–23)
Interindividual Variations in DNA Adduct Levels Assessed by Analysis of Multiple Genetic Polymorphisms in Smokers
Authors: Ketelslegers Hans B. , Gottschalk Ralph W.H. , Godschalk Roger W.L. , Knaapen Ad M. , van Schooten Frederik J. , Vlietinck Robert F.M.H. , Kleinjans Jos C.S. , van Delft Joost H.M.
Published: April 2006

Genetic polymorphisms in genes involved in processes that affect DNA damage may explain part of the large interindividual variation in DNA adduct levels in smokers. We investigated the effect of 19 polymorphisms in 12 genes involved in carcinogen metabolism, DNA repair, and oxidant metabolism on DNA adduct levels (determined by 32P post-labeling) in lymphocytes of 63 healthy Caucasian smokers. The total number of alleles that were categorized as putatively high-risk alleles seemed associated with bulky DNA adduct levels (P = 0.001). Subsequently, to investigate which polymorphisms may have the highest contribution to DNA adduct levels in these smokers, discriminant analysis was done. In the investigated set of polymorphisms, GSTM1*0 (P < 0.001), mEH*2 (P = 0.001), and GPX1*1 (P < 0.001) in combination with the level of exposure (P < 0.001) were found to be key effectors. DNA adduct levels in subjects with a relatively high number of risk alleles of these three genes were >2-fold higher than in individuals not having these risk alleles. Noteworthy, all three genes are involved in deactivation of reactive carcinogenic metabolites. This study shows that analysis of multiple genetic polymorphisms may predict the interindividual variation in DNA adduct levels upon exposure to cigarette smoke. It is concluded that discriminant analysis presents an important statistical tool for analyzing the effect of multiple genotypes on molecular biomarkers. (Cancer Epidemiol Biomarkers Prev 2006;15(4):624–9)
Relationship between Urinary 15-F2t-Isoprostane and 8-Oxodeoxyguanosine Levels and Breast Cancer Risk
Authors: Rossner Pavel , Gammon Marilie D. , Terry Mary Beth , Agrawal Meenakshi , Zhang Fang Fang , Teitelbaum Susan L. , Eng Sybil M. , Gaudet Mia M. , Neugut Alfred I. , Santella Regina M.
Published: April 2006

To evaluate the role of oxidative stress in breast cancer, we measured urinary levels of 15-F2t-isoprostane (15-F2t-IsoP) and 8-oxodeoxyguanosine (8-oxodG) in 400 cases and 401 controls, participants of the Long Island Breast Cancer Study Project. We also analyzed the effect of different factors that are associated with oxidative stress and might influence 15-F2t-IsoP and 8-oxodG levels. We observed a statistically significant trend in breast cancer risk with increasing quartiles of 15-F2t-IsoP levels [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 0.81-1.94; OR, 1.53; 95% CI, 0.99-2.35; OR, 1.88; 95% CI, 1.23-2.88, for the 2nd, 3rd, and 4th quartile relative to the lowest quartile, respectively; Ptrend = 0.002]. Although it is possible that increased levels may reflect the stress associated with recent treatment, the positive association was also observed when the analyses were restricted to case women for whom chemotherapy and radiation therapy had not yet been initiated at the time of the urine collection. The association with the highest quartile compared with lowest quartile of 15-F2t-IsoP was similar across strata of age, physical activity, fruit and vegetable intake, alcohol intake, cigarette smoking, body mass index, and menopausal status. We did not observe any association of breast cancer risk with 8-oxodG levels, but when cases with radiation treatment were removed from the analysis, a significant inverse trend (P = 0.04) was observed. Among controls, levels of 15-F2t-IsoP were higher among current cigarette smokers but did not differ by the amount of physical activity, fruit and vegetable intake, alcohol intake, body mass index, and menopausal status. Among controls, levels of 8-oxodG were higher among postmenopausal women and current and former cigarette smokers but did not differ by the other factors. In summary, our results suggest that urinary markers of lipid peroxidation and oxidative DNA damage may be associated with breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(4):639-44)
Association of theProgesterone ReceptorGene with Breast Cancer Risk: A Single-Nucleotide Polymorphism Tagging Approach
Authors: Pooley Karen A. , Healey Catherine S. , Smith Paula L. , Pharoah Paul D.P. , Thompson Deborah , Tee Louise , West Judith , Jordan Clare , Easton Douglas F. , Ponder Bruce A.J. , Dunning Alison M.
Published: April 2006

Association studies on susceptibility to breast cancer using single nucleotide polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously published, but the results have been inconclusive. We used a comprehensive SNP-tagging approach to search for low-penetrance susceptibility alleles in a study of up to 4,647 cases and 4,564 controls, in a two-stage study design. We identified seven tagging SNPs using genotype data from the National Institute of Environmental Health Sciences (NIEHS) Environmental Genome Project and typed these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284 controls (set 1). Three SNPs showed no evidence for association and were not studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068, rs500760, rs566351, and rs1042838) exhibited significant associations at P < 0.1 using either a heterogeneity or trend test and progressed to be genotyped in set 2. After both stages, only one SNP was significantly associated with an increased risk of breast cancer — the PGR-12 (rs1042638) V660L valine to leucine polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03-1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98-1.73), Phet = 0.008, Ptrend = 0.002]. Similar estimates were obtained in a combined analysis of our data with those from three other published studies. We conclude that the 660L allele may be associated with a moderately increased risk of breast cancer, but that other common SNPs in the PGR gene are unlikely to be associated with a substantial risk of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(4):675–82)
Evidence for an Important Role of Alcohol- and Aldehyde-Metabolizing Genes in Cancers of the Upper Aerodigestive Tract
Authors: Hashibe Mia , Boffetta Paolo , Zaridze David , Shangina Oxana , Szeszenia-Dabrowska Neonila , Mates Dana , Janout Vladimir , Fabiánová Eleonóra , Bencko Vladimir , Moullan Norman , Chabrier Amelie , Hung Rayjean , Hall Janet , Canzian Federico , Brennan Paul
Published: April 2006

Background: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region.

Methods: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2).

Results: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C 350Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C 272Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 −261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AFc) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AFc for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer.

Conclusions: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption. (Cancer Epidemiol Biomarkers Prev 2006;15(4):696–703)
Heme and Chlorophyll Intake and Risk of Colorectal Cancer in the Netherlands Cohort Study
Authors: Balder Helena F. , Vogel Johande , Jansen Margje C.J.F. , Weijenberg Matty P. , van den Brandt Piet A. , Westenbrink Susanne , van der Meer Roelof , Goldbohm R. Alexandra
Published: April 2006

Background: The evidence for red meat as a determinant of colorectal cancer remains equivocal, which might be explained by differences in heme content. Heme is the pro-oxidant, iron-containing porphyrin pigment of meat and its content depends on the type of meat. Chlorophyll from green vegetables might modify this association.

Methods: The Netherlands Cohort Study was initiated in 1986 when a self-administered questionnaire on risk factors for cancer was completed by 120,852 subjects ages 55 to 69 years. After 9.3 years of follow-up through the Cancer Registry, 1,535 incident colorectal cancer cases (869 men and 666 women) were available. Nineteen of the 150 items in the validated dietary questionnaire related to consumption of specific types of fresh and processed meat. Heme iron content was calculated as a type-specific percentage of the total iron content and chlorophyll content of vegetables was derived from the literature.

Results: Multivariate rate ratios for quintiles of heme iron intake and colon cancer were 1.00, 0.98, 1.04, 1.13, and 1.29 (Ptrend = 0.10) among men and 1.00, 1.31, 1.44, 1.18, and 1.20 (Ptrend = 0.56) among women, respectively. No consistent associations were observed for rectal cancer. Rate ratios for colon cancer increased across successive quintiles of the ratio of heme/chlorophyll among men only (1.00, 1.08, 1.01, 1.32, and 1.43; Ptrend = 0.01). No associations were observed between fresh meat and colorectal cancer.

Conclusion: Our data suggest an elevated risk of colon cancer in men with increasing intake of heme iron and decreasing intake of chlorophyll. Further research is needed to confirm these results. (Cancer Epidemiol Biomarkers Prev 2006;15(4):717–25)
Inflammation, Genetic Polymorphisms in Proinflammatory Genes TNF-A, RANTES, and CCR5, and Risk of Pancreatic Adenocarcinoma
Authors: Duell Eric J. , Casella Daniel P. , Burk Robert D. , Kelsey Karl T. , Holly Elizabeth A.
Published: April 2006

Adenocarcinoma of the exocrine pancreas is the fourth leading cause of cancer-related death in men and women in the U.S. Cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. We analyzed cytokine gene polymorphisms as risk factors for pancreatic cancer using questionnaire data obtained by in-person interviews and germ line DNA collected in a population-based case-control study of pancreatic cancer (532 cases and 1,701 controls) conducted in the San Francisco Bay Area. We used mass spectrometry and gel-based methods to genotype 308 cases and 964 population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis and included adjustment for age, sex, and smoking. We assessed potential interactions between these polymorphisms, proinflammatory conditions (e.g., pancreatitis, ulcer, and obesity), and smoking as risk factors for pancreatic cancer. There was no overall association between pancreatic cancer risk and tumor necrosis factor-α (TNF-A −308G/A), regulated upon activation, normally T cell–expressed, and presumably secreted (RANTES −403G/A), and CC chemokine receptor 5 (CCR5-Δ32) polymorphisms. There was a nearly 7-fold increased relative risk estimate for pancreatic cancer in individuals with a history of pancreatitis (adjusted OR, 6.9; 95% CI, 3.4-14.1). Among patients with pancreatic cancer, pancreatitis was significantly associated with TNF-A −308 GA + AA (OR, 3.1; 95% CI, 1.3-7.4) and with RANTES −403 GA + AA (OR, 2.3; 95% CI, 1.0-5.4). There was evidence for a possible interaction between current active smoking and CCR5-32del. Our results lend support for the hypothesis that proinflammatory gene polymorphisms, in combination with proinflammatory conditions, may influence the development of pancreatic cancer. (Cancer Epidemiol Biomakers Prev 2006;15(4):726–31)
A Longitudinal Investigation of Mammographic Density: The Multiethnic Cohort
Authors: Maskarinec Gertraud , Pagano Ian , Lurie Galina , Kolonel Laurence N.
Published: April 2006

Mammographic densities are hypothesized to reflect the cumulative exposure to risk factors that influence breast cancer incidence. This report analyzed percent densities over time and explored predictors of density change in relation to age. The study population consisted of 607 breast cancer cases and 667 frequency matched controls with 1,956 and 1,619 mammographic readings, respectively. Mammograms done over >20 years and before a diagnosis of breast cancer were assessed for densities using a computer-assisted method. Using multilevel modeling to allow for repeated measurements, we estimated the effect of ethnicity, case status, reproductive characteristics, hormonal therapy, body mass index, and soy intake on initial status and longitudinal change. After integrating the area under the percent density curve, cumulative percent density was compared with age-specific breast cancer rates in Hawaii. Percent densities decreased ∼5.6% per 10 years but a nonlinear effect indicated a faster decline earlier in life. Cumulative percent densities and age-specific breast cancer rates increased at very similar rates; both standardized regression coefficients were >0.9. Japanese ancestry, overweight, estrogen/progestin treatment, and, to a lesser degree, estrogen-only therapy predicted a slower decline in densities with age. Case status and adult soy intake were related to higher densities whereas overweight and having any child were associated with lower densities at initial status. Risk factors that influence the decline in mammographic densities over time may be important for breast cancer prevention because cumulative percent densities may reflect the age-related increase in breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(4):732–9)