bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model
Authors: Akiyama Tasuku , Carstens Mirela Iodi , Carstens E.
Published: March 2011

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.
Robotic assistance that encourages the generation of stepping rather than fully assisting movements is best for learning to step in spinally contused rats
Authors: Lee Connie , Won Deborah , Cantoria Mary Jo , Hamlin Marvin , de Leon Ray D.
Published: March 2011

Robotic devices have been developed to assist body weight-supported treadmill training (BWSTT) in individuals with spinal cord injuries (SCIs) and stroke. Recent findings have raised questions about the effectiveness of robotic training that fully assisted (FA) stepping movements. The purpose of this study was to examine whether assist-as-needed robotic (AAN) training was better than FA movements in rats with incomplete SCI. Electromyography (EMG) electrodes were implanted in the tibialis anterior and medial gastrocnemius hindlimb muscles of 14 adult rats. Afterward, the rats received a severe midthoracic spinal cord contusion and began daily weight-supported treadmill training 1 wk later using a rodent robotic system. During training, assistive forces were applied to the ankle when it strayed from a desired stepping trajectory. The amount of force was proportional to the magnitude of the movement error, and this was multiplied by either a high or low scale factor to implement the FA ( n = 7) or AAN algorithms ( n = 7), respectively. Thus FA training drove the ankle along the desired trajectory, whereas greater variety in ankle movements occurred during AAN training. After 4 wk of training, locomotor recovery was greater in the AAN group, as demonstrated by the ability to generate steps without assistance, more normal-like kinematic characteristics, and greater EMG activity. The findings suggested that flexible robotic assistance facilitated learning to step after a SCI. These findings support the rationale for the use of AAN robotic training algorithms in human robotic-assisted BWSTT.
Field Scale Studies on the Spatial Variability of Soil Quality Indicators in Washington State, USA
Authors: Smith Jeffrey L. , Halvorson Jonathan J.
Published: March 2011

Arable lands are needed for sustainable agricultural systems to support an ever-growing human population. Soil quality needs to be defined to assure that new land brought into crop production is sustainable. To evaluate soil quality, a number of soil attributes will need to be measured, evaluated, and integrated into a soil-quality index using the multivariable indicator kriging (MVIK) procedure. This study was conducted to determine the spatial variability and correlation of indicator parameters on a field scale with respect to soil quality and suitability for use with MVIK. The variability of the biological parameters decreased in the order of respiration > enzyme assays and qCO2> microbial biomass C. The distribution frequency of all parameters except respiration were normal although the spatial distribution across the landscape was highly variable. The biological parameters showed little correlation with each other when all data points were considered; however, when grouped in smaller sections, the correlations were more consistent with observed patterns across the field. To accurately assess soil quality, and arable land use, consideration of spatial and temporal variability, soil conditions, and other controlling factors must be taken into account.
Simulation and Statistical Analysis of Market Return Fluctuationby Zipf Method
Authors: Guo Yalong , Wang Jun
Published: March 2011

We investigate the fluctuation behaviors of financial stock markets by Zipf analysis. In the present paper, the empirical research is made to describe ensembles
and specifics of stock price returns for global stock indices, and the corresponding
Zipf distributions are given. First we study the fluctuation behavior of global stock
markets by (m, k)‐Zipf method. Then we consider a dynamic stock price model,
and we analyze the absolute frequencies and the relative frequencies for this financial model. Further, the Zipf distributions of returns for SSE Composite Index are
studied for different time scales.
Generalized Hyers-Ulam Stability of the Pexiderized Cauchy Functional Equation in Non-Archimedean Spaces
Authors: Najati Abbas , Cho YeolJe
Published: March 2011

We prove the generalized Hyers-Ulam stability of the Pexiderized Cauchy functional equation "Equation missing" in non-Archimedean spaces.
Alpha-Hemoglobin-Stabilizing Protein: An Erythroid Molecular Chaperone
Authors: Favero Maria Emília , Costa Fernando Ferreira
Published: March 2011

Alpha-hemoglobin-stabilizing protein (AHSP) is an erythroid-specific protein that acts as a molecular chaperone for the free α chains of hemoglobin. Evidence strongly suggests that AHSP participates in hemoglobin synthesis and may act to neutralize the cytotoxic effects of excess free alpha-globin subunits that accumulate both in normal and beta-thalassemic erythroid precursor cells. As such, AHSP seems to be essential for normal erythropoiesis, and impaired upregulation of AHSP may lead to premature erythroid cell death, resulting in ineffective erythropoiesis. ReducedAHSPmRNA expression has been associated with clinical variability in some cases of β-thalassemia. It has been shown that αHb variants may also impair AHSP-αHb interactions, leading to pathological conditions that resemble α-thalassemia syndromes. The aim of this paper is to summarize current information concerning the structure and function of AHSP, focusing on its role in normal erythropoiesis and its relevance in health and disease.
Potential Impact of B Cells on T Cell Function in Multiple Sclerosis
Authors: Ireland Sara , Monson Nancy
Published: March 2011

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.
On Riemann‐Liouville and Caputo Derivatives
Authors: Li Changpin , Qian Deliang , Chen YangQuan
Published: March 2011

Recently, many models are formulated in terms of fractional derivatives, such as in control processing, viscoelasticity, signal processing, and anomalous diffusion. In the present paper, we further study the important properties of the Riemann‐Liouville (RL) derivative, one of mostly used fractional
derivatives. Some important properties of the Caputo derivative which have not been discussed elsewhere are simultaneously mentioned. The partial fractional derivatives are also introduced. These discussions are beneficial in understanding fractional calculus and modeling fractional equations in science and engineering.
Synchronization of Discrete‐Time Stochastic Neural Networks with Random Delay
Authors: Bao Haibo , Cao Jinde
Published: March 2011

By using a Lyapunov‐Krasovskii functional method and the stochastic
analysis technique, we investigate the problem of synchronization for discrete‐time stochastic neural networks (DSNNs) with random delays. A control law is designed, and sufficient conditions
are established that guarantee the synchronization of two identical DSNNs with random delays.
Compared with the previous works, the time delay is assumed to be existent in a random fashion.
The stochastic disturbances are described in terms of a Brownian motion and the time‐varying
delay is characterized by introducing a Bernoulli stochastic variable. Two examples are given to
illustrate the effectiveness of the proposed results. The main contribution of this paper is that the
obtained results are dependent on not only the bound but also the distribution probability of the
time delay. Moreover, our results provide a larger allowance variation range of the delay, and are
less conservative than the traditional delay‐independent ones.
Pro- and Anti-Inflammatory Cytokines during Immune Stimulation: Modulation of Iron Status and Red Blood Cell Profile
Authors: Koorts A. M. , Levay P. F. , Becker P. J. , Viljoen M.
Published: March 2011

Forty-eight patients were subdivided according to C-reactive protein (CRP) levels, resulting in 19 patients with normal (2.8 ± 2.8 mg/L) and 29 with elevated (82.2 ± 76.2 mg/L) CRP levels. The elevated CRP group had iron and red blood cell (RBC) profiles characteristic of chronic immune stimulation (CIS), and the normal CRP group, profiles of true iron deficiency. Normal relationships between storage iron, bioavailable iron, and RBC indices were absent in the elevated CRP group—implying the role of iron as major determinant of the RBC profile to be diminished during CIS. The elevated CRP group had significant increases in proinflammatory cytokines (INF-γ, TNF-α, Il-1β, Il-6, and Il-8). Anti-inflammatory cytokine levels were normal, except for Il-10, supporting previous indications that Il-10 contributes to reducing bioavailable iron. Regression analysis suggested decreases in transferrin to be related to increases in Il-8 and an increase in ferritin to be related to a decrease in Il-12 levels. TGF-βlevels were positively related to transferrin and negatively to ferritin.
Simulating Smoke Filling in Big Halls by Computational Fluid Dynamics
Authors: Chow W. K. , Chow C. L. , Li S. S.
Published: March 2011

Many tall halls of big space volume were built and, to be built in many construction projects in the Far East, particularly Mainland China, Hong Kong, and Taiwan. Smoke is identified to be the key hazard to handle. Consequently, smoke exhaust systems are specified in the fire code in those areas. An update on applying Computational Fluid Dynamics (CFD) in smoke exhaust design will be presented in this paper. Key points to note in CFD simulations on smoke filling due to a fire in a big hall will be discussed. Mathematical aspects concerning of discretization of partial differential equations and algorithms for solving the velocity‐pressure linked equations are briefly outlined. Results predicted by CFD with different free boundary conditions are compared with those on room fire tests. Standards on grid size, relaxation factors, convergence criteria, and false diffusion should be set up for numerical experiments with CFD.
Common Fixed Point Theorems for a Finite Family of Discontinuous and Noncommutative Maps
Authors: Lin Lai-Jiu , Wang Sung-Yu
Published: March 2011

We study common fixed point theorems for a finite family of discontinuous and noncommutative single-valued functions defined in complete metric spaces. We also study a common fixed point theorem for two multivalued self-mappings and a stationary point theorem in complete metric spaces. Throughout this paper, we establish common fixed point theorems without commuting and continuity assumptions. In contrast, commuting or continuity assumptions are often assumed in common fixed point theorems. We also give examples to show our results. Results in this paper except those that generalized Banach contraction principle and those improve and generalize recent results in fixed point theorem are original and different from any existence result in the literature. The results in this paper will have some applications in nonlinear analysis and fixed point theory.
Molecular Classification of Gastric Cancer: A New Paradigm
Authors: Shah Manish A. , Khanin Raya , Tang Laura , Janjigian Yelena Y. , Klimstra David S. , Gerdes Hans , Kelsen David P.
Published: March 2011

Purpose: Gastric cancer may be subdivided into 3 distinct subtypes—proximal, diffuse, and distal gastric cancer—based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis.

Experimental Design: Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package.

Results: Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach.

Conclusions: Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. Clin Cancer Res; 17(9); 2693–701. ©2011 AACR.
Pulmonary Inflammatory Myofibroblastic Tumor Expressing a Novel Fusion, PPFIBP1–ALK: Reappraisal of Anti-ALK Immunohistochemistry as a Tool for Novel ALK Fusion Identification
Authors: Takeuchi Kengo , Soda Manabu , Togashi Yuki , Sugawara Emiko , Hatano Satoko , Asaka Reimi , Okumura Sakae , Nakagawa Ken , Mano Hiroyuki , Ishikawa Yuichi
Published: March 2011

Purpose: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions. However, detection of some ALK fusions is problematic with conventional anti-ALK immunohistochemistry because of their low expression. By using sensitive immunohistochemistry, therefore, we reassessed “ALK-negative” IMT cases defined with conventional immunohistochemistry (approximately 50% of all examined cases).

Experimental Design: Two cases of ALK-negative IMT defined with conventional anti-ALK immunohistochemistry were further analyzed with sensitive immunohistochemistry [the intercalated antibody-enhanced polymer (iAEP) method].

Results: The two “ALK-negative” IMTs were found positive for anti-ALK immunohistochemistry with the iAEP method. 5′-rapid amplification of cDNA ends identified a novel partner of ALK fusion, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1 (PPFIBP1) in one case. The presence of PPFIBP1–ALK fusion was confirmed with reverse transcriptase PCR, genomic PCR, and FISH. We confirmed the transforming activities of PPFIBP1–ALK with a focus formation assay and an in vivo tumorigenicity assay by using 3T3 fibroblasts infected with a recombinant retrovirus encoding PPFIBP1–ALK. Surprisingly, the fusion was also detected by FISH in the other case.

Conclusions: Sensitive immunohistochemical methods such as iAEP will broaden the potential value of immunohistochemistry. The current ALK positivity rate in IMT should be reassessed with a more highly sensitive method such as iAEP to accurately identify those patients who might benefit from ALK-inhibitor therapies. Novel ALK fusions are being identified in various tumors in addition to IMT, and thus a reassessment of other “ALK-negative” cancers may be required in the forthcoming era of ALK-inhibitor therapy. Clin Cancer Res; 17(10); 3341–8. ©2011 AACR.
Determinants of Mitotic Catastrophe on Abrogation of the G2 DNA Damage Checkpoint by UCN-01
Authors: On Kin Fan , Chen Yue , Tang Ma Hoi , Chow Jeremy P.H. , Poon Randy Y.C.
Published: March 2011

Genotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G2 DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined. In this study, we tracked the fates of individual cells after checkpoint abrogation, focusing in particular on whether they undergo mitotic catastrophe. Surprisingly, while a subset of UCN-01–treated cells were immediately eliminated during the first mitosis after checkpoint abrogation, about half remained viable and progressed into G1. Both the delay of mitotic entry and the level of mitotic catastrophe were dependent on the dose of radiation. Although the level of mitotic catastrophe was specific for different cell lines, it could be promoted by extending the mitosis. In supporting this idea, weakening of the spindle-assembly checkpoint, by either depleting MAD2 or overexpressing the MAD2-binding protein p31comet, suppressed mitotic catastrophe. Conversely, delaying of mitotic exit by depleting either p31comet or CDC20 tipped the balance toward mitotic catastrophe. These results underscore the interplay between the level of DNA damage and the effectiveness of the spindle-assembly checkpoint in determining whether checkpoint-abrogated cells are eliminated during mitosis. Mol Cancer Ther; 10(5); 784–94. ©2011 AACR.
Circulating Levels of Vitamin D and Colon and Rectal Cancer: The Physicians' Health Study and a Meta-analysis of Prospective Studies
Authors: Lee Jung Eun , Li Haojie , Chan Andrew T. , Hollis Bruce W. , Lee I-Min , Stampfer Meir J. , Wu Kana , Giovannucci Edward , Ma Jing
Published: March 2011

It remains unknown whether increased risk with low levels of vitamin D is present for colon and/or rectal cancer. To investigate the association between circulating vitamin D levels and colon and rectal cancer, we examined the associations between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and colon and rectal cancer in the Physicians' Health Study and then conducted a meta-analysis of eight prospective studies of circulating levels of 25(OH)D and colon and rectal cancers, including the Physicians' Health Study. Study-specific ORs and 95% CIs were pooled by using a random-effects model. A total of 1,822 colon and 868 rectal cancers were included in the meta-analysis. We observed a significant inverse association for colorectal cancer (OR = 0.66; 95% CI, 0.54–0.81), comparing top versus bottom quantiles of circulating 25(OH)D levels. The inverse association was stronger for rectal cancer (OR = 0.50 for top versus bottom quantiles; 95% CI, 0.28–0.88) than colon cancer (OR = 0.77; 95% CI, 0.56–1.07; P value for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer. Cancer Prev Res; 4(5); 735–43. ©2011 AACR.
Effects of Tomato- and Soy-Rich Diets on the IGF-I Hormonal Network: A Crossover Study of Postmenopausal Women at High Risk for Breast Cancer
Authors: McLaughlin John M. , Olivo-Marston Susan , Vitolins Mara Z. , Bittoni Marisa , Reeves Katherine W. , Degraffinreid Cecilia R. , Schwartz Steven J. , Clinton Steven K. , Paskett Electra D.
Published: March 2011

To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone–binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 μmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 μmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted. Cancer Prev Res; 4(5); 702–10. ©2011 AACR.
Enforced Expression of miR-101 Inhibits Prostate Cancer Cell Growth by Modulating the COX-2 Pathway In Vivo
Authors: Hao Yubin , Gu Xinbin , Zhao Yuan , Greene Stephen , Sha Wei , Smoot Duane T. , Califano Joseph , Wu T.-C. , Pang Xiaowu
Published: March 2011

It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2–associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1CmiR101) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3′-untranslated region (3′-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1CmiR101 group (0.22 g) than the BPH1Cvec group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression. Cancer Prev Res; 4(7); 1073–83. ©2011 AACR.
In Vivo Longitudinal Imaging of Experimental Human Papillomavirus Infection in Mice with a Multicolor Fluorescence Mini-Endoscopy System
Authors: Mitsunaga Makoto , Kosaka Nobuyuki , Kines Rhonda C. , Roberts Jeffrey N. , Lowy Douglas R. , Schiller John T. , Ishihara Yasushige , Hasegawa Akira , Choyke Peter L. , Kobayashi Hisataka
Published: March 2011

Human papillomavirus (HPV) infection is the most common sexually transmitted infection. Vaccines for HPV infection can reduce the risk of developing cervical cancer. To further improve such vaccines and to explore other methods of preventing or treating viral infection, longitudinal studies in experimental animals are desirable. Here, we describe a newly developed multicolor endoscopic fluorescence imaging system to visualize early HPV infection with fluorescent protein–encoded pseudoviruses (PsV) in the female genital tract of living mice. With this imaging method, the course of HPV PsV infection and the effects of intervention to prevent infection can be monitored in a single mouse over time. Female immunocompetent or athymic mice were pretreated with a vaginal spermicide and then HPV PsV composed of an authentic viral capsid and encapsidating green or red fluorescent protein (GFP or RFP) reporter gene was intravaginally instilled. Expression of GFP or RFP was detected 1 day after PsV challenge, which peaked after 2 or 3 days and decreasing thereafter. No fluorescence was detected in vaccine-treated immunocompetent mice. By using serial infection of the same PsV type (HPV16) encoding either GFP or RFP, different infection patterns of repeated exposure can be monitored. This method offers the ability to monitor experimental virus infections before and after intervention, thereby accelerating the development of appropriate prevention and therapy. Cancer Prev Res; 4(5); 767–73. ©2011 AACR.
Clinical Significance of Pretreatment C-Reactive Protein in Patients with Advanced Nonsquamous, Non-Small Cell Lung Cancer Who Received Gefitinib
Authors: Masago Katsuhiro , Fujita Shiro , Togashi Yosuke , Kim Young Hak , Hatachi Yukimasa , Fukuhara Akiko , Nagai Hiroki , Irisa Kaoru , Sakamori Yuichi , Okuda Chiyuki , Mio Tadashi , Mishima Michiaki
Published: March 2011

Purpose: We examined patients with advanced nonsquamous, non-small cell lung cancer (NSCLC) to evaluate epidermal growth factor receptor (EGFR) mutation status and serum C-reactive protein (CRP) for their associations with response to gefitinib therapy and for prognostic impacts. Methods: Serum levels of CRP from 79 Japanese patients with advanced nonsquamous NSCLC were measured before the start of gefitinib. We used the peptic nucleic acid-locked nucleic acid clamp method to determine their EGFR somatic mutation status. We evaluated the relationship between each independent clinicopathological variable and the response to gefitinib therapy and the risk factors associated with prognosis. Results: Having CRP-positive serum and having wild-type EGFR were both independent negative predictive factors for the response to gefitinib treatment by multivariate logistic regression model analysis. Having CRP-positive serum and having wild-type EGFR were significant independent negative prognostic factors for survival based on multivariate analysis. Conclusions: Having CRP-positive serum predicted a lack of response to gefitinib therapy independent of EGFR mutational status. Both CRP-positive serum and wild-type EGFR were independent poor prognostic factors in patients with nonsquamous NSCLC who received gefitinib therapy.
Castration-Resistant Prostate Cancer: Targeted Therapies
Authors: Leo S. , Accettura C. , Lorusso V.
Published: March 2011

Background: Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. Objective: To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Methods: Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Results: Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. Conclusions: There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future.
In vitro Activities of Erythromycin, Tetracycline and Levofloxacin Alone and in Dual Combinations against Ureaplasma spp.
Authors: Luo Di-Qing , Liu Jing-Ye , Yang Wei , Zhang Bin , Yu Min-Jun , Wu Yi-Mou
Published: March 2011

Purpose: It was the aim of our study to evaluate the in vitro activities of tetracycline (TET), erythromycin (ERY) and levofloxacin (LVX) alone and in dual combinations against ureaplasmas. Methods: The minimum inhibitory concentrations (MICs) of 51 ureaplasmal strains were determined by microdilution assay. Results: TET was the most active when the antibiotics were used alone. The combinations resulted in significantly decreased MICs for every agent compared with the use of single antibiotics (p < 0.05, respectively), except for ERY in the ERY-LVX pair (p > 0.05), and decreased the MICs more significantly in the strains with an MIC ≧4 mg/l compared with MIC <4 mg/l, except for the TET-ERY pair. The ERY-LVX pair increased ERY MICs significantly in the MIC <4 mg/l group (p < 0.05). The combinations resulted in more beneficial MICs in strains where both agents had an MIC ≧4 mg/l compared with those where either had an MIC ≧4 mg/l, as well as in strains where either agent had an MIC <4 mg/l compared with those where both had an MIC <4 mg/l. Conclusions: Drugs in dual combinations always give more beneficial MICs against ureaplasmas than one agent alone. Combinational benefits prefer strains with a higher initial MIC.
Increased Fat Mass and Cardiac Septal Hypertrophy in Newborn Infants of Mothers with Well-Controlled Diabetes during Pregnancy
Authors: Åman J. , Hansson U. , Östlund I. , Wall K. , Persson B.
Published: March 2011

Background: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. Objective: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. Methods: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. Results: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. Conclusion: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.
Enhanced Proinflammatory Cytokine Response to Bacterial Lipopolysaccharide in the Adult Male Rat after either Neonatal or Prepubertal Ablation of Biological Testosterone Activity
Authors: Ongaro Luisina , Castrogiovanni Daniel , Giovambattista Andres , Gaillard Rolf C. , Spinedi Eduardo
Published: March 2011

A sex steroid-dependent modulation of the immune function in mammals is accepted, and evidence suggests that while estrogens enhance, androgens inhibit the immune response. The aim of this study was to explore in the adult male rat the effect of either neonatal flutamide (FTM) treatment or prepubertal orchidectomy (ODX) on endocrine markers in the basal condition and peripheral tumor necrosis factor alpha (TNFα) levels during inflammatory stress. For these purposes, (1) 5-day-old male rats were subcutaneously injected with either sterile vehicle alone or containing 1.75 mg FTM, and (2) 25-day-old male rats were sham operated or had ODX. Rats were sacrificed (at 100 days of age) in the basal condition for determination of peripheral metabolite levels. Additional rats were intravenously injected with bacterial lipopolysaccharide (LPS; 25 µg/kg body weight, i.v.) and bled for up to 4 h. Data indicate that (1) ODX increased peripheral glucocorticoid levels and reduced those of testosterone, whereas FTM-treated rats displayed low circulating leptin concentrations, and (2) LPS-induced TNFα secretion in plasma was significantly enhanced in the FTM and ODX groups. Our study supports that neonatal FTM treatment affected adiposity function, and adds data maintaining that androgens have a suppressive role in proinflammatory cytokine release in plasma during inflammation.
Use of Intravenous Etomidate to Control Acute Psychosis Induced by the Hypercortisolaemia in Severe Paediatric Cushing’s Disease
Authors: Chan L.F. , Vaidya M. , Westphal B. , Allgrove J. , Martin L. , Afshar F. , Hindmarsh P.C. , Savage M.O. , Grossman A.B. , Storr H.L.
Published: March 2011

Background: Psychosis secondary to paediatric Cushing’s disease (CD) is extremely rare and presents a significant management challenge. Method: We report a 14.7-year-old CD patient with acute psychosis and self-inflicted injuries following failed transsphenoidal pituitary surgery. Her mental state rapidly deteriorated precluding medical therapy. Results: Emergency intravenous low-dose etomidate infusion (3–3.5 mg/h) with dose titration according to the serum cortisol combined with a hydrocortisone infusion, in an intensive care setting, was effective in controlling the hypercortisolaemia. Her mental state improved with normalisation of her cortisol levels enabling oral administration of ketoconazole and bilateral adrenalectomy to be performed. Conclusion: This case illustrates the safe and effective use of a low-dose etomidate infusion in an unusual case of paediatric CD.
Influence of Estradiol and Fetal Stress on Luteinizing Hormone, Follicle-Stimulating Hormone, and Prolactin in Late-Gestation Fetal Sheep
Authors: Wood Charles E. , Keller-Wood Maureen
Published: March 2011

Background: Hypotension and reduced cerebral blood flow secondary to brachiocephalic occlusion (BCO) stimulate various homeostatic physiological and endocrine responses. Our previous studies have also suggested a role of estradiol in augmenting the fetal stress response to BCO. Objectives: We tested the hypothesis that gonadotropins and/or prolactin (PRL) are upregulated in fetal pituitary in response to fetal stress and play a role in the response to BCO-induced stress. Methods: We performed 3 studies: one in which we measured ovine fetal pituitary PRL, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) mRNA throughout the latter half of gestation in order to better understand the ontogenetic changes upon which dynamic responses are superimposed; one in which we measured these mRNA abundances in response to BCO and/or estrogen treatment, and one in which we measured plasma LH responses to BCO in chronically catheterized late-gestation fetal sheep. Results: PRL gene expression is increased dramatically in the last 20% of gestation. LH and FSH mRNAs were unchanged except for a transient dip in the expression of LH in the last few days before the normal time of spontaneous parturition. Chronic treatment with estradiol decreased LH and FSH mRNA, but increased PRL mRNA abundance after BCO. In contrast, BCO alone increases the abundance of LH, but not FSH or PRL mRNA in fetal pituitary. Plasma LH concentrations were not increased in response to BCO. Conclusions: We conclude that the late-gestation fetal sheep responds to hypotensive stress with increases in LH mRNA but not LH secretion. LH, FSH and PRL changes are therefore unlikely to contribute to the fetal response to cerebral hypoperfusion.
Chronic Obstructive Pulmonary Disease and Lung Cancer: New Molecular Insights
Authors: Adcock Ian M. , Caramori Gaetano , Barnes Peter J.
Published: March 2011

Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer amongst smokers. Cigarette smoke induces the release of many inflammatory mediators and growth factors including TGF-β, EGFR, IL-1, IL-8 and G-CSF through oxidative stress pathways and this inflammation may persist for decades after smoking cessation. Mucus production is also increased by these inflammatory mediators, further linking airway inflammation to an important mechanism of lung cancer. A greater understanding of the molecular and cellular pathobiology that distinguishes smokers with lung cancer from smokers with and without COPD is needed to unravel the complex molecular interactions between COPD and lung cancer. By understanding the common signalling pathways involved in COPD and lung cancer the hope is that treatments will be developed that not only treat the underlying disease process in COPD, but also reduce the currently high risk of developing lung cancer in these patients.
Psychological Distress in Patients with Benign Voice Disorders
Authors: Siupsinskiene Nora , Razbadauskas Artūras , Dubosas Laimis
Published: March 2011

Objective: The aims of this study were to investigate the frequency of anxiety and depression in patients with benign voice disorders with respect to gender and diagnosis and to determine correlations between psychological distress and some sociodemographic factors and the Voice Handicap Index (VHI). Methods: Psychological distress was assessed for 437 consecutive adult patients with benign voice disorders and 88 healthy controls by a standardized Hospital Anxiety and Depression Scale (HADS). In addition, sociodemographic factors, unhealthy habits and VHI were investigated. Results: Mild to severe HADS-Anxiety scores were seen in 42.1% of the whole patient group, while mild to severe HADS-Depression scores were seen in only 19.2% of patients. The anxiety rate rather than the depression rate in voice patients was found to be significantly higher compared to controls (p < 0.05). Female patients expressed more anxiety than males. HADS-Anxiety scores were similar for most benign voice disorders. The worst depression scores were found in patients with vocal fold paralysis. Higher psychological distress was significantly related to female gender, older age, less education and higher VHI scores. Conclusions: We recommend screening for psychological distress in patients with benign voice disorders using a simple HADS tool to identify those patients who might benefit from a more psychologically based approach to therapy.
Roles of DHA2 Family Transporters in Drug Resistance and Iron Homeostasis in Acinetobacter spp.
Authors: Hassan Karl A. , Brzoska Anthony J. , Wilson Neil L. , Eijkelkamp Bart A. , Brown Melissa H. , Paulsen Ian T.
Published: March 2011

Background:Acinetobacterbaumannii is a major cause of nosocomial infections worldwide due to its fitness within clinical settings and recalcitrance to conventional therapies. The drug: H+ antiporter 2 (DHA2) family export systems encoded by A. baumannii were investigated for their roles in promoting the success ofthis organism as a human pathogen. Methods: Bioinformatic tools were used to identify the DHA2 family transporters encoded by Acinetobacter spp. and establish their phylogenetic relationships. The drug resistance phenotypes conferred by the transporters were tested using both heterologously expressed proteins in Escherichia coli and Acinetobacter deletion mutants. The transcriptional responses of DHA2 family transporter genes to their substrates were established by qRT-PCR. Results: Six highly conserved DHA2 family proteins were identified in A. baumannii. Drug resistance phenotypes were established for two DHA2 family transporters. The expression of a third DHA2 family protein is highly responsive to the availability of iron. The gene encoding this protein is located within a putative siderophore biosynthesis locus, suggesting a physiological role in iron uptake, possibly via the export of a siderophore. Conclusions: These results highlight functions for DHA2 family proteins in both drug resistance and the maintenance of stable cellular physiology, emphasizing their importance in A. baumannii infections.
Socioeconomic Status, Medicaid Coverage, Clinical Comorbidity, and Rehospitalization or Death After an Incident Heart Failure Hospitalization
Authors: Foraker Randi E. , Rose Kathryn M. , Suchindran Chirayath M. , Chang Patricia P. , McNeill Ann M. , Rosamond Wayne D.
Published: March 2011

Background—

Among patients with heart failure (HF), early readmission or death and repeat hospitalizations may be indicators of poor disease management or more severe disease.

Methods and Results—

We assessed the association of neighborhood median household income (nINC) and Medicaid status with rehospitalization or death in the Atherosclerosis Risk in Communities cohort study (1987 to 2004) after an incident HF hospitalization in the context of individual socioeconomic status and evaluated the relationship for modification by demographic and comorbidity factors. We used generalized linear Poisson mixed models to estimate rehospitalization rate ratios and 95% CIs and Cox regression to estimate hazard ratios (HRs) and 95% CIs of rehospitalization or death. In models controlling for race and study community, sex, age at HF diagnosis, body mass index, hypertension, educational attainment, alcohol use, and smoking, patients with a high burden of comorbidity who were living in low-nINC areas at baseline had an elevated hazard of all-cause rehospitalization (HR, 1.40; 95% CI, 1.10 to 1.77), death (HR, 1.36; 95% CI, 1.02 to 1.80), and rehospitalization or death (HR, 1.36; 95% CI, 1.08 to 1.70) as well as increased rates of hospitalization compared to those with a high burden of comorbidity living in high-nINC areas. Medicaid recipients with a low level of comorbidity had an increased hazard of all-cause rehospitalization (HR, 1.19; 95% CI, 1.05 to 1.36) and rehospitalization or death (HR, 1.21; 95% CI, 1.07 to 1.37) and a higher rate of repeat hospitalizations compared to non-Medicaid recipients.

Conclusions—

Comorbidity burden appears to influence the association among nINC, Medicaid status, and rehospitalization and death in patients with HF.
A New Unsupervised Approach to Word Segmentation
Authors: Wang Hanshi , Zhu Jian , Tang Shiping , Fan Xiaozhong
Published: March 2011

This article proposes ESA, a new unsupervised approach to word segmentation. ESA is an iterative process consisting of 3 phases: Evaluation, Selection, and Adjustment. In Evaluation, both certainty and uncertainty of character sequence co-occurrence in corpora are considered as the statistical evidence supporting goodness measurement. Additionally, the statistical data of character sequences with various lengths become comparable with each other by using a simple process called Balancing. In Selection, a local maximum strategy is adopted without thresholds, and the strategy can be implemented with dynamic programming. In Adjustment, a part of the statistical data is updated to improve successive results. In our experiment, ESA was evaluated on the SIGHAN Bakeoff-2 data set. The results suggest that ESA is effective on Chinese corpora. It is noteworthy that the F-measures of the results are basically monotone increasing and can rapidly converge to relatively high values. Furthermore, the empirical formulae based on the results can be used to predict the parameter in ESA to avoid parameter estimation that is usually time-consuming.