bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious cats: effect of removal of vestibular inputs
Authors: Barman Susan M. , Sugiyama Yoichiro , Suzuki Takeshi , Cotter Lucy A. , DeStefino Vincent J. , Reighard Derek A. , Cass Stephen P. , Yates Bill J.
Published: July 2011

Although it is well established that bulbospinal neurons located in the rostral ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve activity and blood pressure, virtually all neurophysiological studies of this region have been conducted in anesthetized or decerebrate animals. In the present study, we used time- and frequency-domain analyses to characterize the naturally occurring discharges of RVLM neurons in conscious cats. Specifically, we compared their activity to fluctuations in carotid artery blood flow to identify neurons with cardiac-related (CR) activity; we then considered whether neurons with CR activity also had a higher-frequency rhythmic firing pattern. In addition, we ascertained whether the surgical removal of vestibular inputs altered the rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons expressed CR activity, although the likelihood of observing a neuron with CR activity in the RVLM varied between recording sessions, even when tracking occurred in a very limited area and was higher after vestibular inputs were surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern coexisted with the CR discharges in some of the RVLM neurons. Additionally, the firing rate of RVLM neurons, including those with CR activity, decreased after vestibular lesions. These findings raise the prospect that RVLM neurons may or may not express rhythmic firing patterns at a particular time due to a variety of influences, including descending projections from higher brain centers and sensory inputs, such as those from the vestibular system.
Motor demand-dependent improvement in accuracy following low-frequency transcranial magnetic stimulation of left motor cortex
Authors: Buetefisch Cathrin M. , Hines Benjamin , Shuster Linda , Pergami Paola , Mathes Adam
Published: July 2011

The role of primary motor cortex (M1) in the control of voluntary movements is still unclear. In brain functional imaging studies of unilateral hand performance, bilateral M1 activation is inconsistently observed, and disruptions of M1 using repetitive transcranial magnetic stimulation (rTMS) lead to variable results in the hand motor performance. As the motor tasks differed qualitatively in these studies, it is conceivable that M1 contribution differs depending on the level of skillfulness. The objective of the present study was to determine whether M1 contribution to hand motor performance differed depending on the level of precision of the motor task. Here, we used low-frequency rTMS of left M1 to determine its effect on the performance of a pointing task that allows the parametric increase of the level of precision and thereby increase the level of required precision quantitatively. We found that low-frequency rTMS improved performance in both hands for the task with the highest demand on precision, whereas performance remained unchanged for the tasks with lower demands. These results suggest that the functional relevance of M1 activity for motor performance changes as a function of motor demand. The bilateral effect of rTMS to left M1 would also support the notion of M1 functions at a higher level in motor control by integrating afferent input from nonprimary motor areas.
Mechanisms and time course of vocal learning and consolidation in the adult songbird
Authors: Warren Timothy L. , Tumer Evren C. , Charlesworth Jonathan D. , Brainard Michael S.
Published: July 2011

In songbirds, the basal ganglia outflow nucleus LMAN is a cortical analog that is required for several forms of song plasticity and learning. Moreover, in adults, inactivating LMAN can reverse the initial expression of learning driven via aversive reinforcement. In the present study, we investigated how LMAN contributes to both reinforcement-driven learning and a self-driven recovery process in adult Bengalese finches. We first drove changes in the fundamental frequency of targeted song syllables and compared the effects of inactivating LMAN with the effects of interfering with N-methyl-d-aspartate (NMDA) receptor-dependent transmission from LMAN to one of its principal targets, the song premotor nucleus RA. Inactivating LMAN and blocking NMDA receptors in RA caused indistinguishable reversions in the expression of learning, indicating that LMAN contributes to learning through NMDA receptor-mediated glutamatergic transmission to RA. We next assessed how LMAN's role evolves over time by maintaining learned changes to song while periodically inactivating LMAN. The expression of learning consolidated to become LMAN independent over multiple days, indicating that this form of consolidation is not completed over one night, as previously suggested, and instead may occur gradually during singing. Subsequent cessation of reinforcement was followed by a gradual self-driven recovery of original song structure, indicating that consolidation does not correspond with the lasting retention of changes to song. Finally, for self-driven recovery, as for reinforcement-driven learning, LMAN was required for the expression of initial, but not later, changes to song. Our results indicate that NMDA receptor-dependent transmission from LMAN to RA plays an essential role in the initial expression of two distinct forms of vocal learning and that this role gradually wanes over a multiday process of consolidation. The results support an emerging view that cortical-basal ganglia circuits can direct the initial expression of learning via top-down influences on primary motor circuitry.
Locomotor-related activity of GABAergic interneurons localized in the ventrolateral region in the isolated spinal cord of neonatal mice
Authors: Nishimaru Hiroshi , Sakagami Hiroyuki , Kakizaki Miyo , Yanagawa Yuchio
Published: July 2011

Inhibitory neurons are an essential element of the locomotor network in the mammalian spinal cord. However, little is known about the firing pattern and synaptic modulation during locomotion in the majority of them. In this study, we performed whole cell recording in visually identified ventrolaterally located GABAergic neurons (VL-GNs) in the rostral (L2 segment) and caudal (L5 segment) lumbar cord using isolated spinal cord preparations taken from glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mouse neonates. These neurons did not respond to electrical stimulation of the ventral root, indicating that they were not Renshaw cells. Ninety-five percent of VL-GNs in the L2 segment and fifty percent of those in the L5 segment showed significant rhythmic firing during locomotor-like rhythmic activity induced by bath application of 5-HT and NMDA. Seventy percent of these neurons fired mainly during the extensor phase, and twenty-five percent fired mainly during the flexor phase. Voltage-clamp recordings revealed that most of these neurons received rhythmic inhibition during the nonfiring phase and excitatory synaptic inputs during the firing phase. Morphological examination of recorded neurons filled with neurobiotin showed that their soma was located lateral to the motoneuron pool and that they extended their processes into the local ipsilateral ventromedial region and dorsal regions. The present study indicates that these GABAergic interneurons located in the ventrolateral region adjacent to the motoneuron pool are rhythmically active during locomotion and involved in the inhibitory modulation of local locomotor network in the lumbar spinal cord.
Altered activation patterns by triceps surae stretch reflex pathways in acute and chronic spinal cord injury
Authors: Frigon Alain , Johnson Michael D. , Heckman C. J.
Published: July 2011

Spinal reflexes are modified by spinal cord injury (SCI) due the loss of excitatory inputs from supraspinal structures and changes within the spinal cord. The stretch reflex is one of the simplest pathways of the central nervous system and was used presently to evaluate how inputs from primary and secondary muscle spindles interact with spinal circuits before and after spinal transection (i.e., spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were evaluated before (i.e., intact state) and after acute spinalization (i.e., acute spinal state). Stretch reflexes were evoked by stretching the left triceps surae (TS) muscles. The force evoked by TS muscles was recorded along with the activity of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal state due to an inability to activate TS muscles, such as soleus (Sol) and lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly recovered but Sol and LG activity remained considerably depressed, despite the fact that injecting clonidine could recruit these muscles during locomotor-like activity. In contrast, other muscles not recruited in the intact state, most notably semitendinosus and sartorius, were strongly activated by stretching TS muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS muscles to multiple hindlimb muscles undergo functional reorganization following spinalization, both acute and chronic. Altered activation patterns by stretch reflex pathways could explain some sensorimotor deficits observed during locomotion and postural corrections after SCI.
Yeast Methylotrophy: Metabolism, Gene Regulation and Peroxisome Homeostasis
Authors: Yurimoto Hiroya , Oku Masahide , Sakai Yasuyoshi
Published: July 2011

Eukaryotic methylotrophs, which are able to obtain all the carbon and energy needed for growth from methanol, are restricted to a limited number of yeast species. When these yeasts are grown on methanol as the sole carbon and energy source, the enzymes involved in methanol metabolism are strongly induced, and the membrane-bound organelles, peroxisomes, which contain key enzymes of methanol metabolism, proliferate massively. These features have made methylotrophic yeasts attractive hosts for the production of heterologous proteins and useful model organisms for the study of peroxisome biogenesis and degradation. In this paper, we describe recent insights into the molecular basis of yeast methylotrophy.
Optimal Approximate Solutions of Fixed Point Equations
Authors: Basha S. Sadiq , Shahzad N. , Jeyaraj R.
Published: July 2011

The main objective of this paper is to present some best proximity point theorems for K‐cyclic mappings and C‐cyclic mappings in the frameworks of metric spaces and uniformly convex Banach spaces, thereby furnishing an optimal approximate solution to the equations of the form Tx = x where T is a non‐self mapping.
Growth and Switching of Ferroelectric Nanocrystals from Ultrathin Film of Copolymer of Vinylidene Fluoride and Trifluoroethylene
Authors: Gaynutdinov R. , Fridkin V. , Kliem H.
Published: July 2011

The ferroelectric nanocrystals of the copolymer of vinylidene fluoride and trifluoroethylene P(VDF-TrFE) were grown from ultrathin Langmuir-Blodgett (LB) films on Si substrate. The annealing of ultrathin LB films with thickness of 3 monolayers (5 nm) in air in paraelectric phase at temperature 125∘C was performed. The self-assembly leads to the growth of nanocrystals of ferroelectric copolymer 15–25 nm thick and 100–200 nm in diameter. The nanocrystals presumably belong to orthorhombic space group, where axis 2 is the direction of spontaneous polarization (and normal to substrate). By means of atomic force microscopy (AFM), the kinetics of ferroelectric nanocrystals growth and their switching were investigated. The obtained results confirm the conclusions that copolymer nanocrystals are candidates for high-density nonvolatile storage media devices.
Fluoride Retention following the Professional Topical Application of 2% Neutral Sodium Fluoride Foam
Authors: Song Wenqun , Toda Shinji , Komiyama Eri , Komiyama Karin , Arakawa Yuki , He Dawei , Arakawa Hirohisa
Published: July 2011

The objective of the present research was to determine the appropriate amount of fluoride to use professional topical application and the residual amounts of fluoride in the oral cavity using a 2% neutral sodium fluoride (NaF) foam with a dedicated tray. Using dentition study models, a method for determining the appropriate amount of NaF foam was investigated. In eight adult subjects, the appropriate amount of NaF foam, the concentration of fluoride in the saliva following professional topical application, and the amount of residual fluoride in the oral cavity following professional topical application was examined. The results indicated that the appropriate amount of NaF foam was approximately 0.8 g, the amount of residual fluoride in the oral cavity was approximately 25% of the amount of foam used.
Hydrogenated Nanocrystalline Silicon Thin Films Prepared by Hot-Wire Method with Varied Process Pressure
Authors: Waman V. S. , Funde A. M. , Kamble M. M. , Pramod M. R. , Hawaldar R. R. , Amalnerkar D. P. , Sathe V. G. , Gosavi S. W. , Jadkar S. R.
Published: July 2011

Hydrogenated nanocrystalline silicon films were prepared by hot-wire method at low substrate temperature (200∘C) without hydrogen dilution of silane (SiH4). A variety of techniques, including Raman spectroscopy, low angle X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), and UV-visible (UV-Vis) spectroscopy, were used to characterize these films for structural and optical properties. Films are grown at reasonably high deposition rates (>15 Å/s), which are very much appreciated for the fabrication of cost effective devices. Different crystalline fractions (from 2.5% to 63%) and crystallite size (3.6–6.0 nm) can be achieved by controlling the process pressure. It is observed that with increase in process pressure, the hydrogen bonding in the films shifts from Si–H to Si–H2and(Si–H2)ncomplexes. The band gaps of the films are found in the range 1.83–2.11 eV, whereas the hydrogen content remains <9 at.% over the entire range of process pressure studied. The ease of depositing films with tunable band gap is useful for fabrication of tandem solar cells. A correlation between structural and optical properties has been found and discussed in detail.
An Overview of Sensitization Dynamics in Ferritic Stainless Steel Welds
Authors: Amuda M. O. H. , Mridha S.
Published: July 2011

Besides the problem of low ductility and poor notch toughness of ferritic stainless steel welds due to the microstructure characteristics of the weld section as a result of the weld heat input rate and the heat transfer factor, susceptibility to intergranular corrosion caused by the depletion of the chromium content of the weld matrix particularly in the HAZ is a major concern limiting the full deployment of the material in certain engineering applications regardless of its attractive economics combined with moderate strength and excellent corrosion resistance in alkali and acidic environments. Several attempts had been made to solve the problem. In the present work, a generic review of the sensitization problem in ferritic stainless steel welds as well as remediation techniques is presented. While stabilization is the most practiced prevention technique, it appears that the control of weld heat input and by extension the cooling rate is the ultimate option to prevent the onset of sensitization and control susceptibility to intergranular corrosion; however, the specific range of welding current and speeds that forms the given range of weld heat input needs to be determined.
Fibrosarcoma of Mandible: A Case Report
Authors: Yuwanati Monal B. , Tupkari J. V.
Published: July 2011

Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely affects the oral cavity and can cause local recurrences or metastasis. In this paper, a case of fibrosarcoma in the posterior area of mandible in a 44-year-old woman is described. Clinical examination revealed a growth on right mandibular third molar region extending on the buccal and the lingual side. There was history of extraction of posterior teeth. Radiologically, there was a diffuse bone loss. Microscopically, the tumor showed an intense proliferation of fibroblasts of variable size and shape. These cells were arranged in parallel bands and partly crossing each other. The cells exhibited increased mitotic activity and nuclear pleomorphism. Immunohistochemically the cells showed immunoreactivity only for vimentin while they exhibited negativity towards S-100 protein, cytokeratin cocktail, HMB-45, desmin, smooth muscle actin, and epithelial membrane antigen (EMA). Based on findings the final diagnosis of fibrosarcoma was made.
Comparative Cytogenetics Analysis of Chlamys farreri, Patinopecten yessoensis, and Argopecten irradians with C0t‐1 DNA by Fluorescence In Situ Hybridization
Authors: Hu Li-Ping , Shang Wen-Cong , Sun Yan , Wang Shan , Ren Xiao-Liang , Huang Xiao-Ting , Bao Zhen-Min
Published: July 2011

The chromosomes of
Chlamys farreri,
Patinopecten yessoensis, and
Argopecten irradians were
studied by FISH using C.
farreriC0t‐1 DNA probes. The results showed that C0t‐1 DNA signals spread on all chromosomes in the three scallops, whereas signal density and intensity were different strikingly. Clustering brighter signals presented in the centromeric and telomeric regions of most C. farreri chromosomes, and in the centromeric or pericentromeric regions of several P. yessoensis chromosomes. Comparative analysis of the mapping indicated a relatively higher homology in the repetitive DNA sequences of the genome between C. farreri and P. yessoensis than that between C. farreri and A. irradians. In addition, FISH showed that the distribution of C0t‐1 DNA clustering signals in C. farreri displayed completely similar signal bands between homologous chromosomes. Based on the C0t‐1 DNA fluorescent bands, a more exact karyotype of C. farreri has been obtained. In this study, the comparative analysis based on C0t‐1 DNA provides a new insight into
the chromosomal reconstructions during the evolution process, and
it is helpful for understanding an important source of genomic
diversity, species relationships, and genome
evolution.
The Possible Role of the Uropygial Gland on Mate Choice in Domestic Chicken
Authors: Hirao Atsushi
Published: July 2011

In avian mating systems, male domestic fowls are polygamous and mate with a number of selected members of the opposite sex. The factors that influence mating preference are considered to be visual cues. However, several studies have indicated that chemosensory cues also affect socio-sexual behavior, including mate choice and individual recognition. The female uropygial gland appears to provide odor for mate choice, as uropygial gland secretions are specific to individual body odor. Chicken olfactory bulbs possess efferent projections to the nucleus taeniae that are involved in copulatory behavior. From various reports, it appears that the uropygial gland has the potential to act as the source of social odor cues that dictate mate choice. In this review, evidence for the possible role of the uropygial gland on mate choice in domestic chickens is presented. However, it remains unclear whether a relationship exists between the uropygial gland and major histocompatibility complex-dependent mate choice.
Integrated Methodologies for the 3D Survey and the Structural Monitoring of Industrial Archaeology: The Case of the Casalecchio di Reno Sluice, Italy
Authors: Bitelli Gabriele , Gatta Giorgia , Girelli Valentina Alena , Vittuari Luca , Zanutta Antonio
Published: July 2011

The paper presents an example of integrated surveying and monitoring activities for the control of an ancient structure, the Casalecchio di Reno sluice, located near Bologna, Italy. Several geomatic techniques were applied (classical topography, high-precision spirit levelling, terrestrial laser scanning, digital close-range photogrammetry, and thermal imagery). All these measurements were put together in a unique reference system and used in order to study the stability and the movements of the structure over the period of time observed. Moreover, the metrical investigations allowed the creation of a 3D model of the structure, and the comparison between two situations, before and after the serious damages suffered by the sluice during the winter season 2008-2009. Along with the detailed investigations performed on individual portions of the structure, an analysis of the whole sluice, carried out at a regional scale, was done via the use of aerial photogrammetry, using both recently acquired images and historical photogrammetric coverage. The measurements were carried out as part of a major consolidation and restoration activity, carried out by the “Consorzio della Chiusa di Casalecchio e del Canale di Reno”.
Retrograde Ureteric Stents via an Ileal Conduit
Authors: Jack Andrew , Burbridge Brent E.
Published: July 2011

Patients having undergone pelvic exenteration with urinary diversion can present with short- and long-term complications such as ureteral strictures, anastomotic leakage, calculi, or fluid collections (abscess, urinoma, lymphocele, or hematoma). A dehiscence resulting in a perineal urinary fistula is an uncommon late complication of urinary diversion surgery; surgical treatment for this complication is less desirable because of postsurgical or radiation-induced pelvic changes that can occur. As a result, nephrostomy or antegrade stenting of the kidneys is more viable. Retrograde ureteric stent insertion is discussed in relation to a patient suffering from ileal conduit dehiscence. The presence of these stents probably helped diminish the potential for complications during subsequent nephrostomy tube insertion.
Perspective: Emerging Challenges in the Treatment of Influenza and Parainfluenza in Transplant Patients
Authors: Moss Ronald B. , Steigbigel Roy T. , Sanders Rebecca L. , Fang Fang
Published: July 2011

Influenza, respiratory synctial virus, and parainfluenza are common respiratory infections in immunocompromised transplant recipients, causing significant morbidity and mortality in this patient population. This paper focuses on influenza and parainfluenza virus infections in transplant patients with emphasis on the pandemic 2009 H1N1 influenza infection. Current antiviral treatment recommendations for influenza and parainfluenza in immunocompromised patients as well as novel investigational therapeutic approaches currently being tested in the clinic are discussed. In addition to the morbidity and mortality caused by these viruses, the development of multidrug resistance leading to transmission of resistant viruses is of great public health concern. The development of effective new therapies for influenza and parainfluenza in these high-risk patients is needed with randomized placebo-controlled studies to assess their clinical utility.
CXCR3 Enhances a T-Cell–Dependent Epidermal Proliferative Response and Promotes Skin Tumorigenesis
Authors: Winkler Ashley E. , Brotman Joshua J. , Pittman Meredith E. , Judd Nancy P. , Lewis James S. , Schreiber Robert D. , Uppaluri Ravindra
Published: July 2011

The chemokine receptor CXCR3 has been proposed to play a critical role in host antitumor responses. In this study, we defined CXCR3-expressing immune cell infiltration in human skin squamous cell carcinomas and then used CXCR3-deficient mice to assess the contribution of CXCR3 to skin tumorigenesis. Our studies employed two established protocols for chemical skin carcinogenesis [methylcholanthrene (MCA) or 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) models]. CXCR3 deletion did not affect tumor development in the MCA model; however, CXCR3 was important in the DMBA/TPA model where gene deletion reduced the incidence of skin tumors. This decreased incidence of skin tumors did not reflect differences in epidermal development but rather was associated with reduced epidermal thickness and proliferation in CXCR3−/− mice, implicating the CXCR3 pathway in DMBA/TPA-induced epidermal inflammation and proliferation. Notably, CXCR3 expressed in CD4+ and CD8+ T cells was found to be important for enhanced epidermal proliferation. Specifically, CXCR3-deficient mice reconstituted with T cells isolated from wild-type mice treated with DMBA/TPA restored wild-type levels of epidermal proliferation in the mutant mice. Taken together, our findings establish that CXCR3 promotes epidermal tumorigenesis likely through a T-cell–dependent induction of keratinocyte proliferation. Cancer Res; 71(17); 5707–16. ©2011 AACR.
Volume of Mammographic Density and Risk of Breast Cancer
Authors: Shepherd John A. , Kerlikowske Karla , Ma Lin , Duewer Frederick , Fan Bo , Wang Jeff , Malkov Serghei , Vittinghoff Eric , Cummings Steven R.
Published: July 2011

Background: Assessing the volume of mammographic density might more accurately reflect the amount of breast volume at risk of malignant transformation and provide a stronger indication of risk of breast cancer than methods based on qualitative scores or dense breast area.

Methods: We prospectively collected mammograms for women undergoing screening mammography. We determined the diagnosis of subsequent invasive or ductal carcinoma in situ for 275 cases, selected 825 controls matched for age, ethnicity, and mammography system, and assessed three measures of breast density: percent dense area, fibroglandular volume, and percent fibroglandular volume.

Results: After adjustment for familial breast cancer history, body mass index, history of breast biopsy, and age at first live birth, the ORs for breast cancer risk in the highest versus lowest measurement quintiles were 2.5 (95% CI: 1.5–4.3) for percent dense area, 2.9 (95% CI: 1.7–4.9) for fibroglandular volume, and 4.1 (95% CI: 2.3–7.2) for percent fibroglandular volume. Net reclassification indexes for density measures plus risk factors versus risk factors alone were 9.6% (P = 0.07) for percent dense area, 21.1% (P = 0.0001) for fibroglandular volume, and 14.8% (P = 0.004) for percent fibroglandular volume. Fibroglandular volume improved the categorical risk classification of 1 in 5 women for both women with and without breast cancer.

Conclusion: Volumetric measures of breast density are more accurate predictors of breast cancer risk than risk factors alone and than percent dense area.

Impact: Risk models including dense fibroglandular volume may more accurately predict breast cancer risk than current risk models. Cancer Epidemiol Biomarkers Prev; 20(7); 1473–82. ©2011 AACR.
Risks for Persistence and Progression by Human Papillomavirus Type 16 Variant Lineages Among a Population-Based Sample of Danish Women
Authors: Gheit Tarik , Cornet Iris , Clifford Gary M. , Iftner Thomas , Munk Christian , Tommasino Massimo , Kjaer Susanne K.
Published: July 2011

Background: Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role.

Methods: HPV16-positive women with normal cytology in a large Danish cohort were reassessed for HPV16 status at 2 years and followed-up for cervical intraepithelial neoplasia 3 or worse (CIN3+) over 11 years through linkage with a national pathology database. Relative risks for clearance, persistence, and progression were compared with different HPV16 variant lineages based upon E6 gene sequencing.

Results: Sixty-two (23.7%) of 261 HPV16 infections were persistent at 2 years, and 32 (51.6%) persistent infections progressed to CIN3+. The majority of baseline infections belonged to the European lineage (97.3%), with EUR-350T and EUR-350G accounting for 61.3% and 36.0% of infections, respectively. At two years, the proportion of HPV16 infections that persisted was significantly higher for EUR-350T (28.2%) than EUR-350G (15.9%) variants (odds ratio = 2.06, 95% CI, 1.04–4.25). This increased risk for persistence was consistent both in the absence (OR = 2.16, 95% CI, 0.84–6.26) or presence (OR = 1.89, 95% CI, 0.76–5.15) of progression to CIN3+. Among persistent HPV16 infections, there was no significant difference in risk of progression to CIN3+ between EUR-350T and EUR-350G sub-lineages, which were both associated with a substantial absolute risk (>50%) of CIN3+.

Conclusions: Significant differences in risk for persistence exist between the HPV16 variants that predominate in Europe.

Impact: Understanding the genetic basis of HPV16 persistence and carcinogenicity may help unravel important interactions between HPV16 and the host immune system. Cancer Epidemiol Biomarkers Prev; 20(7); 1315–21. ©2011 AACR.
Polymorphisms in CYP1A1 and Ethnic-Specific Susceptibility to Acute Lymphoblastic Leukemia in Children
Authors: Swinney Ryan M. , Beuten Joke , Collier Anderson B. , Chen Tina T.-L. , Winick Naomi J. , Pollock Brad H. , Tomlinson Gail E.
Published: July 2011

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL.

Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case–control analysis in Caucasian, Hispanic, and African-American children.

Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18–5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43–7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27–5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13–5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40–7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P = 0.005).

Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population.

Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins. Cancer Epidemiol Biomarkers Prev; 20(7); 1537–42. ©2011 AACR.
Does Exposure to Asbestos Cause Ovarian Cancer? A Systematic Literature Review and Meta-analysis
Authors: Reid Alison , de Klerk Nick , Musk Arthur W. (Bill)
Published: July 2011

Introduction: The asbestos and ovarian cancer relationship is not well understood because of small numbers of women exposed to asbestos, small numbers of cases, and misclassification of peritoneal mesothelioma as ovarian cancer on death certificates. The aim of this study was to conduct a meta-analysis to quantify the evidence that exposure to asbestos causes ovarian cancer.

Methods: Fourteen cohort and two case-control studies were identified in Medline searches from 1950 to 2008.

Results: Statistically significant excess mortality was reported in four of the cohort studies, all of which determined their outcomes from the death certificate. Peritoneal mesotheliomas were reported in these studies, two of which reexamined pathology specimens and reported disease misclassification. Exposure-response relationships were inconsistent. When all studies were included in a meta-analysis, the effect size was 1.75 (95% CI, 1.45–2.10) attenuating to 1.29 (95% CI, 0.97–1.73) in studies with confirmed ovarian cancers.

Conclusion: Taken without further analysis, women thought to have ovarian cancer had an increased rate in the meta-analysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification. Cancer Epidemiol Biomarkers Prev; 20(7); 1287–95. ©2011 AACR.
Racial Differences in Colorectal Cancer Incidence and Mortality in the Women's Health Initiative
Authors: Simon Michael S. , Thomson Cynthia A. , Pettijohn Erin , Kato Ikuko , Rodabough Rebecca J. , Lane Dorothy , Hubbell F. Allan , O'Sullivan Mary Jo , Adams-Campbell Lucille , Mouton Charles P. , Abrams Judith , Chlebowski Rowan T.
Published: July 2011

Background: Colorectal cancer (CRC) incidence and mortality rates are higher in African–Americans as compared with other racial/ethnic groups. The women's health initiative (WHI) study sample was used to determine whether differences in CRC risk factors explain racial/ethnic differences in incidence and mortality.

Methods: The WHI is a longitudinal study of postmenopausal women recruited from 40 centers. Baseline questionnaires were used to collect sociodemographic and health status information. All CRC diagnoses were centrally adjudicated. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by race/ethnicity.

Results: The study sample included 131,481 (83.7%) White, 14,323 (9.1%) African–American, 6,362 (4.1%) Hispanic, 694 (0.4%) Native American and 4,148 (2.6%) Asian/Pacific Islanders. After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was the highest in African–Americans (annualized rate = 0.14%), followed by Whites and Native Americans (0.12% each), Asian/Pacific Islanders (0.10%), and Hispanics (0.08%). After adjustment for age and trial assignment, Hispanics had a lower risk compared with Whites, HR 0.73 (95% CI: 0.54–0.97) (P = 0.03), and African–Americans had a marginally greater risk, HR 1.16 (95% CI: 0.99–1.34), P = 0.06. Multivariable adjustment attenuated the difference in incidence between African–Americans and Whites (HR 0.99, 95% CI: 0.82–1.20), while strengthening the lower HR for Hispanics (HR 0.68, 95% CI: 0.48–0.97).

Conclusions: African–American/White differences in CRC risk are likely due to sociodemographic/cultural factors other than race.

Impact: A number of modifiable exposures could be a focus for reducing CRC risk in African–Americans. Cancer Epidemiol Biomarkers Prev; 20(7); 1368–78. ©2011 AACR.
MicroRNA Signatures: Novel Biomarker for Colorectal Cancer?
Authors: Luo Xiaoya , Burwinkel Barbara , Tao Sha , Brenner Hermann
Published: July 2011

Aberrant microRNA (miRNA) expression might be of potential use as diagnostic and prognostic biomarker for cancers. We reviewed studies published until March 2011 which assessed expression of miRNAs in colorectal cancer (CRC)/adenoma tissue and normal colorectal mucosa and in plasma of CRC/adenoma patients and healthy controls. Overall, 20 studies that investigated miRNA expression in tissue and 3 studies that investigated miRNA levels in plasma were included. A total of 160 miRNAs were found to be dysregulated in CRC. MiR-20a and miR-31 were found to be significantly upregulated in more than one study, and miR-143 and miR-145 were found to be significantly downregulated in CRC tissue in six or more studies. MiR-92a was significantly upregulated in CRC patients in two of the plasma-based studies and in CRC tissue in one of the tissue-based studies. Our results provide timely and relevant information for miRNAs as potential diagnostic biomarkers for CRC. The expression of miRNAs in plasma may be indicative of presence of CRC. Larger diagnostic studies are needed to evaluate potential use of miRNA expression in early detection and diagnosis of CRC. Cancer Epidemiol Biomarkers Prev; 20(7); 1272–86. ©2011 AACR.
Estrogen Metabolism and Exposure in a Genotypic–Phenotypic Model for Breast Cancer Risk Prediction
Authors: Crooke Philip S. , Justenhoven Christina , Brauch Hiltrud , Dawling Sheila , Roodi Nady , Higginbotham Kathryn S. P. , Plummer W. Dale , Schuyler Peggy A. , Sanders Melinda E. , Page David L. , Smith Jeffrey R. , Dupont William D. , Parl Fritz F.
Published: July 2011

Background: Current models of breast cancer risk prediction do not directly reflect mammary estrogen metabolism or genetic variability in exposure to carcinogenic estrogen metabolites.

Methods: We developed a model that simulates the kinetic effect of genetic variants of the enzymes CYP1A1, CYP1B1, and COMT on the production of the main carcinogenic estrogen metabolite, 4-hydroxyestradiol (4-OHE2), expressed as area under the curve metric (4-OHE2-AUC). The model also incorporates phenotypic factors (age, body mass index, hormone replacement therapy, oral contraceptives, and family history), which plausibly influence estrogen metabolism and the production of 4-OHE2. We applied the model to two independent, population-based breast cancer case–control groups, the German GENICA study (967 cases, 971 controls) and the Nashville Breast Cohort (NBC; 465 cases, 885 controls).

Results: In the GENICA study, premenopausal women at the 90th percentile of 4-OHE2-AUC among control subjects had a risk of breast cancer that was 2.30 times that of women at the 10th control 4-OHE2-AUC percentile (95% CI: 1.7–3.2, P = 2.9 × 10−7). This relative risk was 1.89 (95% CI: 1.5–2.4, P = 2.2 × 10−8) in postmenopausal women. In the NBC, this relative risk in postmenopausal women was 1.81 (95% CI: 1.3–2.6, P = 7.6 × 10−4), which increased to 1.83 (95% CI: 1.4–2.3, P = 9.5 × 10−7) when a history of proliferative breast disease was included in the model.

Conclusions: The model combines genotypic and phenotypic factors involved in carcinogenic estrogen metabolite production and cumulative estrogen exposure to predict breast cancer risk.

Impact: The estrogen carcinogenesis–based model has the potential to provide personalized risk estimates. Cancer Epidemiol Biomarkers Prev; 20(7); 1502–15. ©2011 AACR.
Validation of a Light Questionnaire with Real-life Photopic Illuminance Measurements: the Harvard Light Exposure Assessment Questionnaire
Authors: Bajaj Archna , Rosner Bernard , Lockley Steven W. , Schernhammer Eva S.
Published: July 2011

Background: Shift work, which necessitates light exposure at night, is now considered a probable carcinogen. To study the effects of light on chronic diseases like cancer, methods to measure light exposure in large observational studies are needed. We aimed to investigate the validity of self-reported current light exposure.

Methods: We developed a self-administered semiquantitative light questionnaire, the Harvard Light Exposure Assessment (H-LEA) questionnaire, and compared photopic scores derived from this questionnaire with actual photopic and circadian measures obtained from a real-life 7-day light meter application among 132 women (85 rotating night shift workers and 47 day workers) participating in the Nurses' Health Study II.

Results: After adjustment for age, body mass index (BMI), collection day, and night work status, the overall partial Spearman correlation between self-report of light exposure and actual photopic light measurements was 0.72 (P < 0.001; Kendall τ = 0.57) and 0.73 (P < 0.0001; Kendall τ = 0.58) when correlating circadian light measurements. There were only minimal differences in accuracy of self-report of light exposure and photopic or “circadian” light measurement between day (r = 0.77 and 0.78, respectively) and rotating night shift workers (r = 0.68 and 0.69, respectively).

Conclusions: The results of this study provide evidence of the criterion validity of self-reported light exposure using the H-LEA questionnaire.

Impact: This questionnaire is a practical method of assessing light exposure in large-scale epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 20(7); 1341–9. ©2011 AACR.
State Disparities in Colorectal Cancer Mortality Patterns in the United States
Authors: Naishadham Deepa , Lansdorp-Vogelaar Iris , Siegel Rebecca , Cokkinides Vilma , Jemal Ahmedin
Published: July 2011

Background: Colorectal cancer (CRC) mortality rates have been decreasing for many decades in the United States, with the decrease accelerating in the most recent time period. The extent to which this decrease varies across states and its influence on the geographic patterns of rates is unknown.

Methods: We analyzed the temporal trend in age-standardized CRC death rates for each state from 1990 to 2007 using joinpoint regression. We also examined the change in death rates between 1990–1994 and 2003–2007 using rate ratios with 95% confidence intervals and illustrated the change in pattern using maps. The relationship between the change in mortality rates and CRC screening rates for 2004 by state was examined using Pearson's correlation.

Results: CRC mortality rates significantly decreased in all states except Mississippi between 1990 and 2007 based on the joinpoint model. The decrease in death rates between 1990–1994 and 2003–2007 ranged from 9% in Alabama to greater than 33% in Massachusetts, Rhode Island, New York, and Alaska; Mississippi and Wyoming showed no significant decrease. Generally, the northeastern states showed the largest decreases, whereas southern states showed the smallest decreases. The highest CRC mortality rates shifted from the northeastern states during 1990 to 1994 to the southern states along the Appalachian corridor during 2003 to 2007. The decrease in CRC mortality rates by state correlated strongly with uptake of screening (r = −0.65, P < 0.0001).

Conclusions: Progress in reducing CRC mortality varies across states, with the Northeast showing the most progress and the South showing the least progress.

Impact: These findings highlight the need for wider dissemination of CRC screening. Cancer Epidemiol Biomarkers Prev; 20(7); 1296–302. ©2011 AACR.
Chemokine RANTES Promoter Dimorphisms and Hepatocellular Carcinoma Occurrence in Patients with Alcoholic or Hepatitis C Virus–Related Cirrhosis
Authors: Charni Faten , Sutton Angela , Rufat Pierre , Laguillier Christelle , Mansouri Abdellah , Moreau Richard , Ganne-Carrié Nathalie , Trinchet Jean-Claude , Beaugrand Michel , Charnaux Nathalie , Nahon Pierre
Published: July 2011

Background: This study explores the influence of two functional genetic polymorphisms in the regulated on activation in normal T-cell expressed and secreted(RANTES) promoter on the risk of hepatocellular carcinoma (HCC) occurrence in patients with alcoholic or Hepatitis C Virus (HCV)-related cirrhosis.

Methods: RANTES C-28G and G-403A promoter dimorphisms and RANTES serum levels were assessed in 243 HCV-infected patients and 253 alcoholic patients, included at the time of diagnosis of cirrhosis and prospectively followed-up.

Results: During a mean follow-up time of 76 months, 137 (27.6%) patients developed HCC and 170 (34.2%) died or were transplanted. During follow-up, patients with alcoholic cirrhosis and bearing two copies of the RANTES G-403 variant (2G-403 genotype, n = 156/253) had a higher rate of HCC occurrence compared with patients carrying at least one RANTES A-403 allele (26.3% vs. 8.2%, P = 0.0004). The RANTES 2G-403 genotype was a risk factor for HCC occurrence [HR = 3.0 (1.3–5.8); first quartile time to HCC occurrence: 60 vs. 120 months; LogRank = 0.007] and death [HR = 1.4 (1.0–2.0); median time to death: 55 vs. 79 months; LogRank = 0.01] in this subgroup. Carriage of the RANTES 2G-403 genotype was not associated with HCC development or death in patients with HCV-related cirrhosis. The RANTES C-28G dimorphism did not influence the occurrence of death or HCC in either cohort of patients.

Conclusion: This study suggests an influence of the chemokine RANTES G-403A dimorphism on the occurrence of HCC in patients with alcoholic cirrhosis.

Impact: Our findings provide clues for future studies on RANTES gene in relation to HCC susceptibility. Cancer Epidemiol Biomarkers Prev; 20(7); 1439–46. ©2011 AACR.
Age-Period-Cohort Models in Cancer Surveillance Research: Ready for Prime Time?
Authors: Rosenberg Philip S. , Anderson William F.
Published: July 2011

Standard descriptive methods for the analysis of cancer surveillance data include canonical plots based on the lexis diagram, directly age-standardized rates (ASR), estimated annual percentage change (EAPC), and joinpoint regression. The age-period-cohort (APC) model has been used less often. Here, we argue that it merits much broader use. First, we describe close connections between estimable functions of the model parameters and standard quantities such as the ASR, EAPC, and joinpoints. Estimable functions have the added value of being fully adjusted for period and cohort effects, and generally more precise. Second, the APC model provides the descriptive epidemiologist with powerful new tools, including rigorous statistical methods for comparative analyses, and the ability to project the future burden of cancer. We illustrate these principles by using invasive female breast cancer incidence in the United States, but these concepts apply equally well to other cancer sites for incidence or mortality. Cancer Epidemiol Biomarkers Prev; 20(7); 1263–8. ©2011 AACR.
Prevention of Colitis-Associated Colorectal Cancer with 8-Hydroxydeoxyguanosine
Authors: Ock Chan Young , Kim Eun-Hee , Hong Hua , Hong Kyung Sook , Han Young-Min , Choi Ki-Seok , Hahm Ki-Baik , Chung Myung-Hee
Published: July 2011

Colitis-associated cancer (CAC) is one of clear examples of inflammation–carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1–STAT3 and COX–NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG–containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG–containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG–treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC. Cancer Prev Res; 4(9); 1507–21. ©2011 AACR.