bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Immunity Through Autophagy
Authors: Münz Christian
Published: December 2008

Next to the proteasome, autophagy is the main catabolic pathway for the degradation of cytoplasmic constituents. The immune system uses it both as an effector mechanism to clear intracellular pathogens and as a mechanism to monitor its products for evidence of pathogen invasion and cellular transformation. Because autophagy delivers intracellular material for lysosomal degradation, its products are primarily loaded onto MHC class II molecules and are able to stimulate CD4+ T cells. This process might shape the self-tolerance of the CD4+ T cell repertoire and stimulate CD4+ T cell responses against pathogens and tumors. Beyond antigen processing, autophagy's role in cell survival is to assist the clonal expansion of B and T cells for efficient adaptive immune responses. These immune-enhancing functions make autophagy an attractive target for therapeutic manipulation in human disease.
Xanthogranulomatous Endometritis: A Challenging Imitator of Endometrial Carcinoma
Authors: Doğan-Ekici A. Işın , Usubütün Alp , Küçükali Türkan , Ayhan Ali
Published: December 2008

Xanthogranulomatous inflammation is a distinguished histopathological entity affecting several organs, predominantly the kidney and gallbladder. So far, only a small number of cases of xanthogranulomatous inflammation occurring in female genital tract have been described, most frequently affecting the endometrium and histologically characterized by replacement of endometrium by xanthogranulomatous inflammation composed of abundant foamy histiocytes, siderophages, giant cells, fibrosis, calcification and accompanying polymorphonuclear leucocytes, plasma cells and lymphocytes of polyclonal origin. We present a case of a 69-year-old female complained of post menopausal bleeding and weight loss. Clinical preliminary diagnoses were endometrial carcinoma or hyperplasia and ultrasound was supposed to be endometrial malignancy, hyperplasia or pyometra by radiologist. Histopathological examination of uterus revealed xanthogranulomatous endometritis. Since xanthogranulomatous endometritis may mimic endometrial malignancy clinically and pathologically as a result of the replacement of the endometrium and occasionally invasion of the myometrium by friable yellowish tissue composed of histiocytes, knowledge of this unusual inflammatory disease is needed for both clinicians and pathologists.
Human Papillomavirus in Endometrial Adenocarcinomas: Infectious Agent or a Mere “Passenger”?
Authors: Giatromanolaki A. , Sivridis E. , Papazoglou D. , Koukourakis M. I. , Maltezos E.
Published: December 2008

Aims. To investigate the possible association of human papillomavirus (HPV) with endometrial hyperplasias and neoplasia. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas?Methods. Twenty-five endometrial adenocarcinomas of the endometrioid cell type, with and without squamous differentiation, and twenty-four endometrial hyperplasias of various forms (simple, complex, and atypical) were analyzed for the presence of type 16 and 18 HPV by the polymerase chain reaction (PCR). The results were related to histopathological features of the tumour, and the patients' age, and prognosis.Results. Six of 25 endometrial adenocarcinomas were HPV 16-positive (24%), and 5 of 25 (20%) were HPV 18-positive. Simple endometrial hyperplasias was associated somewhat more commonly with HPV 16 and 18 (2/8 and 1/8 cases, resp) than hyperplasias progressing to endometrial adenocarcinomas, namely, atypical endometrial hyperplasia (1/8 and 0/8 cases, resp.). None of the positive cases in the series, whether hyperplastic or neoplastic, demonstrated cytological evidence of HPV infection. There was no relation between HPV-positive cases and squamous differentiation, depth of myometrial invasion, lymphatic involvement, lymphocytic response, patients' age, or prognosis.Conclusion. It appears that the presence of HPV in the endometrium, as detected by PCR, does not play any role in the initiation or prognosis of endometrial adenocarcinoma.
Genital Tract Interleukin-8 but not Interleukin-1βor Interleukin-6 Concentration is Associated with Bacterial Vaginosis and Its Clearance in HIV-Infected and HIV-Uninfected Women
Authors: Losikoff Phyllis , Fichorova Raina , Snyder Brad , Rodriguez Irma , Cu-Uvin Susan , Harwell Joseph , Mayer Kenneth H.
Published: December 2008

Genital tract infections and cytokine perturbations are associated with increased HIV acquisition and transmission. We measured the relationship between bacterial vaginosis (BV) and concentrations of Interleukin-8 (IL-8), Interleukin-1β(IL-1β), and Interleukin-6 (IL-6) in cervicovaginal lavage (CVL) specimens collected longitudinally from 16 HIV-infected and 8 HIV-uninfected high-risk women. CVL samples were analyzed when women presented with BV, and at their next visit, after successful treatment, when BV was cleared. A subset of participants had cytokine levels evaluated at three consecutive clinic visits: before developing BV, at the time of BV diagnosis, and after clearing BV. Significantly higher IL-8, but not IL-1βor IL-6 levels were present when women had active BV compared to when BV was absent. Trends in cytokine levels were similar for HIV-infected and HIV-uninfected women. BV in these women was associated with significantly higher concentrations of genital tract IL-8 which decreased 2.4 fold when BV was cleared.
GPS Carrier‐Phase Time Transfer Using Single‐Difference Integer Ambiguity Resolution
Authors: Delporte J. , Mercier F. , Laurichesse D. , Galy O.
Published: December 2008

GPS is widely used for time and frequency transfer. To estimate the clock difference between two ground
stations, a single baseline solution can be performed using external products for the modelling of the geometrical effects (constellation ephemeris and station coordinates). The baseline solution relies on a single‐difference formulation, using code and phase ionosphere‐free measurements. The phase ambiguities are usually adjusted as floating parameters. Such solutions give very good results when modelling hypotheses are consistent between the external solution (e.g., GPS orbits) and the baseline solution.
However, the frequency bias in the computed clock is very sensitive to discrepancies in the models, and is only observed thanks to the code measurement, with limitations due to the noise. Here, we propose to solve the integer ambiguities on single‐difference phase measurements. The advantage is the complete elimination of the clock drifts observed in floating ambiguities solutions. This formulation allows also a reliable continuous connection between overlapping clock solutions (jumps between such solutions can be completely eliminated). Several time transfer results are analyzed and compared to TWSTFT. The methodology has been extended to a network of stations using integer ambiguities on zero‐difference measurements. The corresponding results are given for a few European stations.
MMSE Reconstruction for 3D Freehand Ultrasound Imaging
Authors: Huang Wei , Zheng Yibin
Published: December 2008

The reconstruction of 3D ultrasound (US) images from
mechanically registered, but otherwise irregularly positioned,
B‐scan slices is of great interest in image guided therapy procedures.
Conventional 3D ultrasound algorithms have low computational complexity, but the reconstructed volume suffers from severe speckle contamination. Furthermore, the current method cannot reconstruct uniform high‐resolution data from several low‐resolution B‐scans. In this paper, the minimum mean‐squared error (MMSE) method is applied to 3D ultrasound reconstruction. Data redundancies due to overlapping samples as well as correlation of the target and speckle are naturally accounted for in the MMSE reconstruction algorithm. Thus, the reconstruction process unifies the interpolation and spatial compounding. Simulation results for synthetic US images are presented to demonstrate the excellent reconstruction.
Human Granulocytic Ehrlichiosis Complicating Early Pregnancy
Authors: Muffly Tyler , McCormick T. Chad , Cook Christopher , Wall Jeffrey
Published: December 2008

Background. The goal of this case is to review the zoonotic infection, human granulocytic ehrlichiosis, presenting with pyrexia.Case. A 22-year-old multigravid female presented to the emergency department with a painful skin rash, high fever, and severe myalgias. The patient underwent a diagnostic evaluation for zoonotic infections due to her geographical and seasonal risk factors. Treatment of human granulocytic ehrlichiosis was successful though the patient spontaneously aborted presumably due to the severity of the acute illness.Conclusion. Treatment of human granulocytic ehrlichiosis in pregnancy presents unique challenges. Management of pyrexia during pregnancy is limited to external cooling in the setting of thrombocytopenia and elevated aminotransferases. Extensive counseling regarding teratogenic potential of medications allows the patient to weigh the pros and cons of treatment.
Tests of Fit for the Logarithmic Distribution
Authors: Best D. J. , Rayner J. C. W. , Thas O.
Published: December 2008

Smooth tests for the logarithmic distribution are compared with three tests: the first is a test due to Epps and is based on a probability generating function, the second is the Anderson-Darling test, and the third is due to Klar and is based on the empirical integrated distribution function. These tests all have substantially better power than the traditional Pearson-Fisher X2 test of fit for the logarithmic. These traditional chi-squared tests are the only logarithmic tests of fit commonly applied by ecologists and other scientists.
Tetracycline Effects onCandida AlbicansVirulence Factors
Authors: McCool Logan , Mai Hanh , Essmann Michael , Larsen Bryan
Published: December 2008

Object. To determine if tetracycline, previously reported to increase the probability of developing symptomatic vaginal yeast infections, has a direct effect onCandida albicansgrowth or induction of virulent phenotypes.Method. In vitro, clinical isolates of yeast were cultivated with sublethal concentrations of tetracycline and yeast cell counts, hyphal formation, drug efflux pump activity, biofilm production, and hemolysin production were determined by previously reported methods.Results. Tetracycline concentrations above 150 μg/mL inhibitedCandida albicans, but at submicrogram/mL, a modest growth increase during the early hours of the growth curve was observed. Tetracycline did not inhibit hyphal formation at sublethal concentrations. Hypha formation appeared augmented by exposure to tetracycline in the presence of chemically defined medium and especially in the presence of human serum. Efflux pumpCDR1was upregulated and a nonsignificant trend toward increased biofilm formation was noted.Conclusion. Tetracycline appears to have a small growth enhancing effect and may influence virulence through augmentation of hypha formation, and a modest effect on drug efflux and biofilm formation, although tetracycline did not affect hemolysin. It is not clear if the magnitude of the effect is sufficient to attribute vaginitis following tetracycline treatment to direct action of tetracycline on yeast.
High Rate of Severe Fetal Outcomes Associated with Maternal Parvovirus B19 Infection in Pregnancy
Authors: Beigi Richard H. , Wiesenfeld Harold C. , Landers Daniel V. , Simhan Hyagriv N.
Published: December 2008

Objective. To augment the understanding of parvovirus B19 infection in pregnancy with respect to maternal characteristics and their corresponding fetal outcomes.Study Design. Retrospective case-series of all women referred to Magee-Women_s Hospital with serologically-documented parvovirus B19 infection during pregnancy from 1998–2001.Results. All 25 cases that are available for analysis occurred from January through June. The frequency of cases varied substantially from year to year, with 14 cases in 1998, 0 cases in 1999 and 2000, and 11 cases in 2001. In contrast to previous reports, the minority of women [4/25(16%)] experienced symptoms attributable to parvovirus B-19 infection although 3 of 25 (12%) fetuses developed hydrops fetalis and 4/25 (16%) suffered an intrauterine of fetal death.Conclusions. These findings suggest that parvovirus B19 infection in pregnancy follows seasonal and annual trend variation, may produce a lower frequency of maternal symptoms and a higher fetal loss rate than previously reported.Synopsis. Maternal parvovirus B19 infection follows seasonal and annual variation is often asymptomatic and may have higher fetal loss rates than previously reported. Continued surveillance is warranted.
The Relationship between Cocaine Use and Human Papillomavirus Infections in HIV-Seropositive and HIV-Seronegative Women
Authors: Minkoff Howard , Zhong Ye , Strickler Howard D. , Watts D. Heather , Palefsky Joel M. , Levine Alexandra M. , D'Souza Gypsyamber , Howard Andrea A. , Plankey Michael , Massad L. Stewart , Burk Robert
Published: December 2008

Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV.Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types.Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09–1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27–2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97).Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.
About the Stability and Positivity of a Class of Discrete Nonlinear Systems of Difference Equations
Authors: De la Sen M.
Published: December 2008

This paper investigates stability conditions and positivity of the solutions of a coupled set of nonlinear difference equations under very generic conditions of the nonlinear real functions which are assumed to be bounded from below and nondecreasing. Furthermore, they are assumed to be linearly upper bounded for sufficiently large values of their arguments. These hypotheses have been stated in 2007 to study the conditions permanence.
The NALP3/Cryopyrin‐Inflammasome Complex is Expressed	in LPS‐Induced Ocular Inflammation
Authors: González-Benítez José F. , Juárez-Verdayes Marco A. , Rodríguez-Martínez Sandra , Cancino-Diaz Mario E. , García-Vázquez Francisco , Cancino-Diaz Juan C.
Published: December 2008

In the inflammosome complex, NALP3 or NALP1 binds to ASC and activates caspase‐1 which induces IL‐1β. In murine LPS‐induced ocular inflammation, the production of IL‐1β is increased. We suggest that NALP3‐ or NALP1‐inflammasome complex can be participating in the LPS‐induced ocular inflammation. In this work, eye, brain, testis, heart, spleen, and lung were obtained from C3H/HeN mice treated with LPS for 3 to 48 hours, and the expression of NALP1b, NALP3, ASC, caspase‐1, IL‐1β, and IL‐18 was determined. Infiltrated leukocytes producing IL‐1β in the anterior chamber were found at 12‐hour posttreatment. A high upregulated expression of NALP3, ASC, caspase‐1, IL‐1β, and IL‐18 was found at the same time when infiltrated leukocytes were observed. NALP1b was not detected in the eye of treated mice. NALP3 was also overexpressed in heart and lung. These results suggest that NALP3‐, but not NALP1‐inflammosome complex, is participating in the murine LPS‐induced ocular inflammation.
Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome
Authors: Singh Rabindra P. , Grimer Robert J. , Bhujel Nabina , Carter Simon R. , Tillman Roger M. , Abudu Adesegun
Published: December 2008

We have retrospectively analysed the experience of a musculoskeletal oncological unit in the management of adult head and neck soft tissue sarcomas from 1990 to 2005. Thirty-six patients were seen, of whom 24 were treated at this unit, the remainder only receiving advice. The median age of the patients was 46 years. Most of the sarcomas were deep and of high or intermediate grade with a median size of 5.5 cm. Eleven different histological subtypes were identified. Wide excision was possible only in 21% of the cases. 42% of the patients developed local recurrence and 42% developed metastatic disease usually in the lungs. Overall survival was 49% at 5 years. Tumour size was the most important prognostic factor. Adult head and neck soft tissue sarcomas have a high mortality rate with a high risk of local recurrence and metastatic disease. The rarity of the disease would suggest that centralisation of care could lead to increased expertise and better outcomes.
A Wave‐Spectrum Analysis of Urban Population Density: Entropy, Fractal, and Spatial Localization
Authors: Chen Yanguang
Published: December 2008

The method of spectral analysis is employed to research the spatial dynamics of urban population distribution. First of all, the negative exponential model is derived in a new way by using an entropy‐maximizing idea. Then an approximate scaling relation between wave number and spectral density is derived by Fourier transform of the negative exponential model. The theoretical results suggest the locality of urban population activities. So the principle of entropy maximization can be utilized to interpret the locality and localization of urban morphology. The wave‐spectrum model is applied to the city in the real world, Hangzhou, China, and spectral exponents can give the dimension values of the fractal lines of urban population profiles. The changing trend of the fractal dimension does reflect the localization of urban population growth and diffusion. This research on spatial dynamics of urban evolvement is significant for modeling spatial complexity and simulating spatial complication of city systems by cellular automata.
Online Preconcentration and Determination of Trace Amounts of Zinc in Nature Waters
Authors: Wei Liang , Zhang Xinshen , Dai Yichun , Huang Jin , Xie Yong-hong , Xiao Kai
Published: December 2008

A simple, sensitive, reliable and flexible flow injection spectrophotometric method is proposed for on-line preconcentration and determination of trace amounts of zinc in water. At the presence of Tween-80 in pH 9.3 buffer solutions, the shade of color of Zn (II)-PAN complex is in a linear relation to the zinc amount at the point of the maximum absorption peak of 560 nm. The optimal experimental conditions, including reaction conditions and preconcentration conditions, had been obtained. The linear range of the proposed method was between 2.0 and 360 μg L−1and the detection limit was 0.42 μg L−1. The relative standard deviation was 3.55% and 2.14% for 5.0 μg L−1and 50 μg L−1of zinc standard solution (n=8). The method had been successfully applied to zinc determination in water samples and the analytical results were satisfactory.
Determining Effective Spraying Periods to Control Malaria via Indoor Residual Spraying in Sub-Saharan Africa
Authors: Smith Robert J. , Hove-Musekwa Senelani D.
Published: December 2008

Indoor residual spraying—spraying insecticide inside houses to kill mosquitoes—is an important method for controlling malaria vectors in sub-Saharan Africa. We propose a mathematical model for both regular and non-fixed spraying, using impulsive differential equations. First, we determine the stability properties of the nonimpulsive system. Next, we derive minimal effective spraying intervals and the degree of spraying effectiveness required to control mosquitoes when spraying occurs at regular intervals. If spraying is not fixed, then we determine the “next best” spraying times. We also consider the effects of climate change on the prevalence of mosquitoes. We show that both regular and nonfixed spraying will result in a significant reduction in the overall number of mosquitoes, as well as the number of malaria cases in humans. We thus recommend that the use of indoor spraying be re-examined for widespread application in malaria-endemic areas.
Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor
Authors: Agnew Kathy J. , Aura Jan , Nunez Norma , Lee Zandra , Lawler Rick , Richardson Carol E. , Culhane Jennifer , Hitti Jane
Published: December 2008

The presence of semen in vaginal fluid, as identified by an acid phosphatase spot test, does not influence vaginal proinflammatory cytokine concentrations.Objective: determine whether semen, as detected by acid phosphatase, influences vaginal cytokines or secretory leukocyte protease inhibitor concentrations.Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test.Results: of 138 subjects, 28 (20%) had acid phosphatase detected; of these, only 19 (68%) reported recent intercourse and 3 (11%) had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase.Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations.
On the Asymptotic Approach to Thermosolutal Convection in Heated Slow Reactive Boundary Layer Flows
Authors: Shateyi Stanford , Sibanda Precious , Motsa Sandile S.
Published: December 2008

The study sought to investigate thermosolutal convection and stability of two dimensional disturbances
imposed on a heated boundary layer flow over a semi‐infinite horizontal plate composed of a
chemical species using a self‐consistent asymptotic method. The chemical species reacts as it diffuses
into the nearby fluid causing density stratification and inducing a buoyancy force. The existence of
significant temperature gradients near the plate surface results in additional buoyancy and decrease in
viscosity. We derive the linear neutral results by analyzing asymptotically the multideck structure of
the perturbed flow in the limit of large Reynolds numbers. The study shows that for small Damkohler
numbers, increasing buoyancy has a destabilizing effect on the upper branch Tollmien‐Schlichting (TS)
instability waves. Similarly, increasing the Damkohler numbers (which corresponds to increasing the
reaction rate) has a destabilizing effect on the TS wave modes. However, for small Damkohler numbers,
negative buoyancy stabilizes the boundary layer flow.
On the Global Asymptotic Stability of a Second‐Order System of Difference Equations
Authors: Yalcinkaya Ibrahim
Published: December 2008

A sufficient condition is obtained for the global asymptotic
stability of the following system of difference equations zn+1 = (tnzn−1 + a)/(tn + zn−1),   tn+1 = (zntn−1 + a)/(zn + tn−1),   n = 0, 1, 2, …, where the parameter aϵ(0, ∞) and the initial values (zk, tk)ϵ(0, ∞) (for k = −1, 0).
Embodiment, Multimodality, and Composition: Convergent Themes across HCI and Education for Mixed-Reality Learning Environments
Authors: Birchfield David , Thornburg Harvey , Megowan-Romanowicz M. Colleen , Hatton Sarah , Mechtley Brandon , Dolgov Igor , Burleson Winslow
Published: December 2008

We present concurrent theoretical work from HCI and Education that reveals a convergence of trends focused on the importance of three themes: embodiment, multimodality, and composition. We argue that there is great potential for truly transformative work that aligns HCI and Education research, and posit that there is an important opportunity to advance this effort through the full integration of the three themes into a theoretical and technological framework for learning. We present our own work in this regard, introducing the Situated Multimedia Arts Learning Lab (SMALLab). SMALLab is a mixed-reality environment where students collaborate and interact with sonic and visual media through full-body, 3D movements in an open physical space. SMALLab emphasizes human-to-human interaction within a multimodal, computational context. We present a recent case study that documents the development of a new SMALLab learning scenario, a collaborative student participation framework, a student-centered curriculum, and a three-day teaching experiment for seventy-two earth science students. Participating students demonstrated significant learning gains as a result of the treatment. We conclude that our theoretical and technological framework can be broadly applied in the realization of mixed reality, student-centered learning environments.
Generalized Newman Phenomena and Digit Conjectures on Primes
Authors: Shevelev Vladimir
Published: December 2008

We prove that the ratio of the Newman sum over numbers
multiple of a fixed integer, which is not a multiple of 3, and the Newman
sum over numbers multiple of a fixed integer divisible by 3 is o(1)
when the upper limit of summing tends to infinity. We also discuss a
connection of our results with a digit conjecture on primes.
The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model
Authors: Worley Kevin C. , Roberts Scott W. , Bawdon Roger E.
Published: December 2008

Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete.Objective. To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model.Study Design. Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20–30 fold, and 600–800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the antipyrine reference method.Results. OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of , suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations.Conclusions. Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.
Structural and Physical Properties ofFe2O3-B2O3-V2O5Glasses
Authors: Kundu Virender , Dhiman R. L. , Maan A. S. , Goyal D. R.
Published: December 2008

The structural and physical properties ofxFe2O3-(40-x)B2O3-60V2O5  (0≤x≤20)glass system have been investigated. The samples were prepared by normal melt-quench technique. The structural changes were inferred by means of FTIR by monitoring the infrared (IR) spectra in the spectral range 600–4000cm-1. The absence of boroxol ring (806 cm-1) in the present glass system suggested that these glasses consist of randomly connectedBO3andBO4units. The conversion ofBO3toBO4andVO5toVO4tetrahedra along with the formation of non-bridging oxygen's (NBOs) attached to boron and vanadium takes place in the glasses under investigation. The density and molar volume of the present glass system were found to depend onFe2O3content. DC conductivity of the glass system has been determined in the temperature range 310–500 K. It was found that the general behavior of electrical conductivity was similar for all glass compositions and found to increase with increasing iron content. The parameters such as activation energy, average separation between transition metal ions (TMIs), polaron radius, and so forth have been calculated in adiabatic region and are found consistent with Mott's model of phonon-assisted polaronic hopping.
Using Discharge Abstracts to Evaluate a Regional Perinatal Network: Assessment of the Linkage Procedure of Anonymous Data
Authors: Quantin Catherine , Ferdynus Cyril , Avillach Paul , Gouyon Béatrice , Sagot Paul , Gouyon Jean-Bernard
Published: December 2008

To assess the Burgundy perinatal network (18 obstetrical units; 18 500 births per year), discharge abstracts and additional data were collected for all mothers and newborns. In accordance with French law, data were rendered anonymous before statistical analysis, and were linked to patients using a specific procedure. This procedure allowed data concerning each mother to be linked to those for her newborn(s). This study showed that all mothers and newborns were included in the regional database; the data for all mothers were linked to those for their infant(s) in all cases. Additional data (gestational age) were obtained for 99.9% of newborns.
Lowering Caveolin-1 Expression in Human Vascular Endothelial Cells Inhibits Signal Transduction in Response to Shear Stress
Authors: van der Meer A. D. , Kamphuis M. M. J. , Poot A. A. , Feijen J. , Vermes I.
Published: December 2008

Vascular endothelial cells have an extensive response to physiological levels of shear stress. There is evidence that the protein caveolin-1 is involved in the early phase of this response. In this study, caveolin-1 was downregulated in human endothelial cells by RNAi. When these cells were subjected to a shear stress of 15 dyn/cm2for 10 minutes, activation of Akt and ERK1/2 was significantly lower than in control cells. Moreover, activation of Akt and ERK1/2 in response to vascular endothelial growth factor was significantly lower in cells with low levels of caveolin-1. However, activation of integrin-mediated signaling during cell adhesion onto fibronectin was not hampered by lowered caveolin-1 levels. In conclusion, caveolin-1 is an essential component in the response of endothelial cells to shear stress. Furthermore, the results suggest that the role of caveolin-1 in this process lies in facilitating efficient VEGFR2-mediated signaling.
Eosinophil infiltration, gastric juice and serum eosinophil cationic protein levels in Helicobacter pylori‐associated chronic gastritis and gastric ulcer
Authors: Aydemir Selim , Tekin Isak Ozel , Numanoglu Gamze , Borazan Ali , Ustundag Yucel
Published: December 2008

INTRODUCTION: Helicobacter pylori is one of the main causes of gastroduodenal diseases, such as chronic gastritis and peptic ulcer. It has been shown that eosinophils increase in the stomach in H. pylori infection. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils. However, there are no sufficient data about the role of ECP in H. pylori infection and its effect on ulcer development. In this study we investigated the gastric eosinophilic infiltration, gastric juice and serum ECP levels in patients with chronic gastritis and gastric ulcer associated with H. pylori.

Materials and methods: Forty‐four H. pylori‐positive and 20 H. pylori‐negative patients who underwent upper gastrointestinal system endoscopy after admitting with dyspeptic complaints were enrolled in the study. Twenty‐one of the H. Pylori‐positive patients had gastric ulcer while 23 patients had none. During endoscopy, multiple gastric biopsies and juices were taken. In gastric biopsies, H. pylori and eosinophilic infiltration were assessed. Additionally, gastric juice and serum ECP levels were measured.

Results: Eosinophil infiltration, gastric juice ECP levels, and gastric juice/serum ECP ratios in the H. pylori‐positive group were greater than in the H. pylori‐negative group (p < 0.01). There was no statistically significant difference regarding serum ECP levels between the two groups (p > 0.05). When H. pylori‐positive patients were compared with regard to gastric ulcer presence, however, there was no significant difference in gastric eosinophil infiltration, gastric juice ECP levels, serum ECP levels, and gastric juice/serum ECP ratios (p > 0.05).

Conclusion: The results of this study suggest that eosinophils and eosinophil‐released ECP may contribute to inflammatory changes seen in chronic gastritis, whereas there is no proof that they play a role in ulcer development.
Secular Trends in the Incidence of and Risk Factors for Ischemic Stroke and Its Subtypes in Japanese Population
Authors: Kubo Michiaki , Hata Jun , Doi Yasufumi , Tanizaki Yumihiro , Iida Mitsuo , Kiyohara Yutaka
Published: December 2008

Background—

The study of long-term trends in the incidence of and risk factors for ischemic stroke subtypes could offer insights into primary and secondary prevention.

Methods and Results—

We established 3 cohorts of residents ≥40 years of age in 1961, 1974, and 1988 in the Japanese community of Hisayama. Morphological examinations by autopsy or brain imaging were performed on most of the ischemic stroke cases developed in these cohorts. When 13-year follow-up data were compared, the age-adjusted incidence of ischemic stroke and lacunar infarction declined significantly from the first to the third cohort for both sexes, whereas the incidences of atherothrombotic and cardioembolic infarction did not change during this period. Hypertension was a powerful risk factor for the development of ischemic stroke, and improvement of hypertension control would have largely influenced this declining trend: The age- and sex-adjusted hazard ratio of hypertension decreased from 3.25 (95% CI 2.17 to 4.86) in the first cohort to 1.83 (1.29 to 2.58) in the third cohort. A rapid increase in the prevalence of metabolic disorders may have offset the impact of improvements in hypertension control and resulted in a slowdown of the decline in the incidence of ischemic stroke in the cohorts in the present study; however, hypertension still makes a large contribution to the development of ischemic stroke.

Conclusions—

These findings suggest that in the Japanese population, the incidence of ischemic stroke has declined significantly over the past 40 years, probably owing to better management of hypertension. There is a need for greater primary prevention efforts in the treatment of hypertension and metabolic disorders.
Platelet P2Y
12
Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis
Authors: Evans D.J.W. , Jackman L.E. , Chamberlain J. , Crosdale D.J. , Judge H.M. , Jetha K. , Norman K.E. , Francis S.E. , Storey R.F.
Published: December 2008

Background—

Platelets are believed to play an important role in atherogenesis and the vessel response to vascular injury. The P2Y
12
receptor (P2Y
12
) plays a central role in amplifying platelet aggregation, dense granule and α-granule secretion, P-selectin expression, microparticle formation, and procoagulant membrane changes, regardless of the activating stimulus. We hypothesized that P2Y
12
deficiency might reduce the vessel wall response to vascular injury as well as thrombosis in murine vascular injury models.

Methods and Results—

P2Y
12
-deficient (−/−) mice and littermate controls (+/+) were bred on a C57 BL/6 background. In vivo murine models of arterial injury were employed alone and in combination with bone marrow transplantation to investigate the role of P2Y
12
in the vessel wall response to arterial injury and thrombosis. At 21 days after ferric chloride injury, neointima formation in P2Y
12
−/−
arteries was significantly less than that observed in control strain arteries (
P
<0.025). In agreement with this, the intima-media ratio was significantly greater in femoral wire-injured arteries from P2Y
12
+/+
compared with P2Y
12
−/−
animals (
P
<0.05). Bone marrow transplantation was used to examine the importance of vessel wall P2Y
12
versus platelet P2Y
12
. Analysis of arterial sections from chimeric animals at 21 days after injury revealed a smaller intima-media ratio in −/− to +/+ animals than in the positive (+/+ to +/+) control group (
P
<0.01).

Conclusions—

These data demonstrate a role for platelet P2Y
12
in the vessel wall response to arterial injury and thrombosis. This illustrates the manner in which platelets may contribute to atherogenesis and restenosis.
Elevated Heat Shock Protein 60 Levels Are Associated With Higher Risk of Coronary Heart Disease in Chinese
Authors: Zhang Xiaomin , He Mei'an , Cheng Longxian , Chen Ying , Zhou Li , Zeng Hesong , Pockley A. Graham , Hu Frank B. , Wu Tangchun
Published: December 2008

Background—

Although heat shock protein 60 (Hsp60) is implicated in the pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is uncertain. This study explored the influence of circulating Hsp60 on CHD in a large case-control study, as well as the impact of acute myocardial infarction on Hsp60 levels in a prospective study.

Methods and Results—

Plasma Hsp60 and anti-Hsp60 antibody levels were determined by immunoassay. In the case-control study (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher in patients with CHD and were related to CHD (OR comparing extreme quartiles=4.14,
P
<0.0001). This association remained after adjustment for traditional risk factors (
P
for trend <0.0001). Individuals having high levels of Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater than the median of 38.42 U/mL) were at a greater risk of CHD than those with low levels (OR 2.30,
P
<0.0001). Stronger additive effects (OR 14.04,
P
<0.0001) were apparent at higher Hsp60 and anti-Hsp60 antibody levels (>1000 ng/mL and greater than the median of 38.42 U/mL, respectively). The simultaneous presence of high Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes were cumulatively associated with CHD. Individuals who had any 4 or more of these 5 factors had an OR of 38.61 for CHD (
P
<0.0001) compared with individuals who had none of these factors. For the prospective study, blood was drawn from 20 patients immediately after admission for acute myocardial infarction and 2, 3, and 7 days thereafter. Hsp60 levels were significantly higher on the day of and the day after arrival than 7 days after an acute myocardial infarction (
P
=0.011 and
P
=0.026, respectively).

Conclusions—

Elevated Hsp60 levels are associated with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine to increase this risk. In addition, acute myocardial infarction induces Hsp60 release.
Impact of Statin Therapy on Central Aortic Pressures and Hemodynamics
Authors: Williams Bryan , Lacy Peter S. , Cruickshank J. Kennedy , Collier David , Hughes Alun D. , Stanton Alice , Thom Simon , Thurston Herbert
Published: December 2008

Background—

Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation–Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension.

Methods and Results—

CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, −0.1 mm Hg [95% CI, −1.8 to 1.6],
P
=0.9; change in brachial pulse pressure, −0.02 mm Hg [95% CI, −1.6 to 1.6],
P
=0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, −0.5 mm Hg [95% CI, −2.3 to 1.2],
P
=0.5; change in aortic pulse pressure, −0.4 mm Hg [95% CI, −1.9 to 1.0],
P
=0.6) and had no influence on augmentation index (change in augmentation index, −0.4%; 95% CI, −1.7 to 0.8;
P
=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, −1.3 to 1.8;
P
=0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure–lowering treatment strategy in the factorial design.

Conclusions—

Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.
Critical Role of Transcription Factor Cyclic AMP Response Element Modulator in β
1
-Adrenoceptor–Mediated Cardiac Dysfunction
Authors: Lewin Geertje , Matus Marek , Basu Abhijit , Frebel Karin , Rohsbach Sebastian Pius , Safronenko Andrej , Seidl Matthias Dodo , Stümpel Frank , Buchwalow Igor , König Simone , Engelhardt Stefan , Lohse Martin J. , Schmitz Wilhelm , Müller Frank Ulrich
Published: December 2008

Background—

Chronic stimulation of the β
1
-adrenoceptor (β
1
AR) plays a crucial role in the pathogenesis of heart failure; however, underlying mechanisms remain to be elucidated. The regulation by transcription factors cAMP response element-binding protein (CREB) and cyclic AMP response element modulator (CREM) represents a fundamental mechanism of cyclic AMP–dependent gene control possibly implicated in β
1
AR-mediated cardiac deterioration.

Methods and Results—

We studied the role of CREM in β
1
AR-mediated cardiac effects, comparing transgenic mice with heart-directed expression of β
1
AR in the absence and presence of functional CREM. CREM inactivation protected from cardiomyocyte hypertrophy, fibrosis, and left ventricular dysfunction in β
1
AR-overexpressing mice. Transcriptome and proteome analysis revealed a set of predicted CREB/CREM target genes including the cardiac ryanodine receptor, tropomyosin 1α, and cardiac α-actin as altered on the mRNA or protein level along with the improved phenotype in CREM-deficient β
1
AR-transgenic hearts.

Conclusions—

The results imply the regulation of genes by CREM as an important mechanism of β
1
AR-induced cardiac damage in mice.
Impact of Kidney Disease and Blood Pressure on the Development of Cardiovascular Disease
Authors: Ninomiya Toshiharu , Kiyohara Yutaka , Tokuda Yosuke , Doi Yasufumi , Arima Hisatomi , Harada Akiko , Ohashi Yasuo , Ueshima Hirotsugu
Published: December 2008

Background—

Kidney disease is associated with an increased risk of cardiovascular disease (CVD); however, there have been few well-designed prospective studies of this issue in Asian populations. Recent epidemiological studies have suggested that a lower blood pressure level may be associated with an increased risk of CVD in individuals with kidney dysfunction.

Methods and Results—

Using data from 10 community-based cohort studies in Japan, we conducted follow-up on a total of 30 657 individuals 40 to 89 years of age without preexisting CVD or kidney failure and examined the relationship between reduced glomerular filtration rate (GFR) and the risk of CVD. During an average 7.4-year follow-up, 727 individuals experienced CVD. The age- and sex-adjusted incidence of CVD increased significantly in subjects with GFR of 60 to 89 mL · min
−1
· 1.73 m
−2
(4.3 per 1000 person-years,
P
=0.002) and in those with a GFR <60 mL · min
−1
· 1.73 m
−2
(6.5,
P
<0.001) compared with those with a GFR ≥90 mL · min
−1
· 1.73 m
−2
(2.9). Even after adjustment for potential confounding factors, subjects with a GFR <60 mL · min
−1
· 1.73 m
−2
had a 57% (95% CI 14% to 115%) greater risk of CVD than those with a GFR ≥90 mL · min
−1
· 1.73 m
−2
. The multivariate-adjusted hazard ratios of CVD increased in a log-linear manner with elevations in blood pressure levels, regardless of GFR levels (all
P
for trend <0.01).

Conclusions—

Our findings suggest that a reduced GFR is a significant risk factor for CVD in the general Japanese population. Additionally, a log-linear association of blood pressure level with CVD risk was observed, without evidence of a J-curve association, regardless of GFR levels.
Acute Doxorubicin Cardiotoxicity Is Associated With p53-Induced Inhibition of the Mammalian Target of Rapamycin Pathway
Authors: Zhu Wuqiang , Soonpaa Mark H. , Chen Hanying , Shen Weihua , Payne R. Mark , Liechty Edward A. , Caldwell Randall L. , Shou Weinian , Field Loren J.
Published: December 2008

Background—

Doxorubicin is used to treat childhood and adult cancer. Doxorubicin treatment is associated with both acute and chronic cardiotoxicity. The cardiotoxic effects of doxorubicin are cumulative, which limits its chemotherapeutic dose. Free radical generation and p53-dependent apoptosis are thought to contribute to doxorubicin-induced cardiotoxicity.

Methods and Results—

Adult transgenic (MHC-CB7) mice expressing cardiomyocyte-restricted dominant-interfering p53 and their nontransgenic littermates were treated with doxorubicin (20 mg/kg cumulative dose). Nontransgenic mice exhibited reduced left ventricular systolic function (predoxorubicin fractional shortening [FS] 61±2%, postdoxorubicin FS 45±2%, mean±SEM,
P
<0.008), reduced cardiac mass, and high levels of cardiomyocyte apoptosis 7 days after the initiation of doxorubicin treatment. In contrast, doxorubicin-treated MHC-CB7 mice exhibited normal left ventricular systolic function (predoxorubicin FS 63±2%, postdoxorubicin FS 60±2%,
P
>0.008), normal cardiac mass, and low levels of cardiomyocyte apoptosis. Western blot analyses indicated that mTOR (mammalian target of rapamycin) signaling was inhibited in doxorubicin-treated nontransgenic mice but not in doxorubicin-treated MHC-CB7 mice. Accordingly, transgenic mice with cardiomyocyte-restricted, constitutively active mTOR expression (MHC-mTORca) were studied. Left ventricular systolic function (predoxorubicin FS 64±2%, postdoxorubicin FS 60±3%,
P
>0.008) and cardiac mass were normal in doxorubicin-treated MHC-mTORca mice, despite levels of cardiomyocyte apoptosis similar to those seen in doxorubicin-treated nontransgenic mice.

Conclusions—

These data suggest that doxorubicin treatment induces acute cardiac dysfunction and reduces cardiac mass via p53-dependent inhibition of mTOR signaling and that loss of myocardial mass, and not cardiomyocyte apoptosis, is the major contributor to acute doxorubicin cardiotoxicity.