bluuebunny/crossref_metadata_2025 huggingface dataset:
Public policy activity related to accessibility in the United States
Authors: Lazar Jonathan
Published: January 2011

The year 2010 has been very active in the area of public policy related to interface accessibility within the US. A number of events, which have been planned or discussed in previous years, have come to fruition. Other events have occurred which have started new policy processes related to accessibility.
The Acute Respiratory Distress Syndrome: Pathogenesis and Treatment
Authors: Matthay Michael A. , Zemans Rachel L.
Published: January 2011

The acute respiratory distress syndrome (ARDS) causes 40% mortality in approximately 200,000 critically ill patients annually in the United States. ARDS is caused by protein-rich pulmonary edema that causes severe hypoxemia and impaired carbon dioxide excretion. The clinical disorders associated with the development of ARDS include sepsis, pneumonia, aspiration of gastric contents, and major trauma. The lung injury is caused primarily by neutrophil-dependent and platelet-dependent damage to the endothelial and epithelial barriers of the lung. Resolution is delayed because of injury to the lung epithelial barrier, which prevents removal of alveolar edema fluid and deprives the lung of adequate quantities of surfactant. Lymphocytes may play a role in resolution of lung injury. Mortality has been markedly reduced with a lung-protective ventilatory strategy. However, there is no effective pharmacologic therapy, although cell-based therapy and other therapies currently being tested in clinical trials may provide novel treatments for ARDS.
EGFR Mutations and Lung Cancer
Authors: da Cunha Santos Gilda , Shepherd Frances A. , Tsao Ming Sound
Published: January 2011

Epidermal growth factor receptor (EGFR) is a transmembrane protein with cytoplasmic kinase activity that transduces important growth factor signaling from the extracellular milieu to the cell. Given that more than 60% of non–small cell lung carcinomas (NSCLCs) express EGFR, EGFR has become an important therapeutic target for the treatment of these tumors. Inhibitors that target the kinase domain of EGFR have been developed and are clinically active. More importantly, such tyrosine kinase inhibitors (TKIs) are especially effective in patients whose tumors harbor activating mutations in the tyrosine kinase domain of the EGFR gene. More recent trials have suggested that for advanced NSCLC patients with EGFR mutant tumors, initial therapy with a TKI instead of chemotherapy may be the best choice of treatment. Therefore, mutation testing is mandatory to identify these patients, given that selection based only on clinico-pathologic characteristics is inadequate. We review the role of EGFR mutations in the diagnosis and management of NSCLC.
Mechanisms of Leukocyte Transendothelial Migration
Authors: Muller William A.
Published: January 2011

Neither the innate nor adaptive immune system “responds” unless leukocytes cross blood vessels. This process occurs through diapedesis, in which the leukocyte moves in an ameboid fashion through tightly apposed endothelial borders and, in some cases, through the endothelial cell itself. This review focuses on the active role of the endothelial cell in diapedesis. Several mechanisms play a critical role in transendothelial migration, including signals derived from clustering of apically disposed intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, disruption or loosening of adherens junctions, and targeted recycling of platelet/endothelial cell adhesion molecule and other molecules from the recently described lateral border recycling compartment. Surprisingly, many of the same molecules and mechanisms that regulate paracellular migration also control transcellular migration. A hypothesis that integrates the various known mechanisms of transmigration is proposed.
Molecular Genetics of Colorectal Cancer
Authors: Fearon Eric R.
Published: January 2011

Over the past three decades, molecular genetic studies have revealed some critical mutations underlying the pathogenesis of the sporadic and inherited forms of colorectal cancer (CRC). A relatively limited number of oncogenes and tumor-suppressor genes—most prominently the APC, KRAS, and p53 genes—are mutated in a sizeable fraction of CRCs, and a larger collection of genes that are mutated in subsets of CRC have begun to be defined. Together with DNA-methylation and chromatin-structure changes, the mutations act to dysregulate conserved signaling networks that exert context-dependent effects on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Much work remains to be done to fully understand the nature and significance of the individual and collective genetic and epigenetic defects in CRC. Some key concepts for the field have emerged, two of which are emphasized in this review. Specifically, the gene defects in CRC often target proteins and pathways that exert pleiotropic effects on the cancer cell phenotype, and particular genetic and epigenetic alterations are linked to biologically and clinically distinct subsets of CRC.
Starting in Immunology by Way of Immunopathology
Authors: Unanue Emil R.
Published: January 2011

This article comments on my trajectory first from Havana as a medical student, to Pittsburgh as a pathology intern, then to La Jolla. It reviews my initial experience in immunology research at the Scripps Research Institute in the early 1960s. Under Frank Dixon, my work examined how antibodies to the glomerular basement membrane (GBM) cause disease. I present these studies in the broader context of immunological renal injury. The early studies by Dixon and his group examining the models of acute or chronic serum sickness were major for our understanding of renal and vascular pathology. I review them because of their historical importance in immunopathology and also cover facets of Dixon's overall contributions to immunology. The studies in serum sickness and anti-GBM nephritis led to an understanding of autoimmune glomerulonephritides, the first proven autoantibody-induced diseases.
Biomedical Differences Between Human and Nonhuman Hominids: Potential Roles for Uniquely Human Aspects of Sialic Acid Biology
Authors: Varki Nissi M. , Strobert Elizabeth , Dick Edward J. , Benirschke Kurt , Varki Ajit
Published: January 2011

Although humans are genetically very similar to the evolutionarily related nonhuman hominids (chimpanzees, bonobos, gorillas, and orangutans), comparative studies suggest a surprising number of uniquely human differences in the incidence and/or severity of biomedical conditions. Some differences are due to anatomical changes that occurred during human evolution. However, many cannot be explained either by these changes or by known environmental factors. Because chimpanzees were long considered models for human disease, it is important to be aware of these differences, which appear to have been deemphasized relative to similarities. We focus on the pathophysiology and pathobiology of biomedical conditions that appear unique to humans, including several speculative possibilities that require further study. We pay particular attention to the possible contributions of uniquely human changes in the biology of cell-surface sialic acids and the proteins that recognize them. We also discuss the metabolic incorporation of a diet-derived nonhuman sialic acid, which generates a novel xeno-autoantigen reaction, and chronic inflammation known as xenosialitis.
Zebrafish Models for Cancer
Authors: Liu Shu , Leach Steven D.
Published: January 2011

First established as a valuable vertebrate model system for studying development, zebrafish have emerged as an attractive animal system for modeling human cancers. Major technical advances have been essential for the generation of zebrafish cancer models relevant to human diseases. These models develop tumors in various organ sites that bear striking resemblance to human malignances, both histologically and genetically. Thus, the focus of cancer research in zebrafish has transcended the need to validate zebrafish as a viable model organism to study cancer biology. With the significant advantages of in vivo imaging, the power of forward genetics, well-established high efficiency for transgenesis, and ease of transplantation, further exploration of the zebrafish cancer models not only will generate unique insights into underlying mechanisms of cancer but will also provide platforms useful for drug discovery.
Is there a Learning Curve for Pancreaticoduodenectomy after Fellowship Training?
Authors: Hardacre Jeffrey M.
Published: January 2011

Background. Limited data exist regarding a learning curve for pancreaticoduodenectomy (PD). This study examines whether a learning curve exists for the performance of PD after fellowship training. Methods. Review of the outcomes of a single surgeon's first 60 PDs after completion of specialty training in pancreatic surgery. Results. Sixty PDs were performed over five years, with the final 30 being done in the last 15 months. Patient age and gender did not differ between the first 30 and last 30 patients. When comparing the first 30 PDs to the second 30 PDs, significant improvements were found in operative time (463 versus 388 minutes), length of stay (10 versus 7 days), and receipt of adjuvant therapy (58% versus 91%). There were no significant differences found in mortality (7% versus 0%), complications (60% versus 50%), readmissions (18% versus 20%), or margin-positive resections (25% versus 24%). Conclusion. Even with extensive training in pancreatic surgery, a learning curve exists for the performance of PD. With experience, improvements were made in operative time, but more importantly in patient outcomes including length of stay and receipt of adjuvant therapy.
On Mappings with Contractive Iterate at a Point in Generalized Metric Spaces
Authors: Gajić Ljiljana , Lozanov-Crvenković Zagorka
Published: January 2011

Using the setting of generalized metric space, the so-called G-metric space, fixed point theorems for mappings with a contractive and a generalized contractive iterate at a point are proved. These results generalize some comparable results in the literature. A common fixed point result is also proved.
Pseudoangiomatous Stromal Hyperplasia: A Case Report
Authors: Masannat Yazan A. , Whitehead Stephen , Hawley Ian , Apthorp Lesley , Shah Elizabeth F.
Published: January 2011

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferating breast condition. It was first reported in 1986 when Vuitch, Rosen, and Erlandson described nine cases of benign well-circumscribed, breast masses that simulated vascular lesions consisting of mammary stromal proliferations (Vuitch et al. (1986)). Since then there have been few reported cases of PASH in the literature (Taira et al. (2005)). We describe a large PASH, mimicking inflammatory carcinoma in a young lady that was excised with excellent cosmetic results.
Multiobjective Optimal Control of HIV Dynamics
Authors: Zarei Hassan , Kamyad Ali Vahidian , Effati Sohrab
Published: January 2011

Various aspects of the interaction of HIV with the human immune system can be modeled by a system of ordinary differential equations. This model is utilized, and a multiobjective optimal control problem (MOOCP) is proposed to maximize the CD4+ T cells population and minimize both the viral load and drug costs. The weighted sum method is used, and continuous Pareto optimal solutions are derived by solving the corresponding optimality system. Moreover, a model predictive control (MPC) strategy is applied, with the final goal of implementing Pareto optimal structured treatment interruptions (STI) protocol. In particular, by using a fuzzy approach, the MOOCP is converted to a single‐objective optimization problem to derive a Pareto optimal solution which among other Pareto optimal solutions has the best satisfaction performance. Then, by using an embedding method, the problem is transferred into a modified problem in an appropriate space in which the existence of solution is guaranteed by compactness of the space. The metamorphosed problem is approximated by a linear programming (LP) model, and a piecewise constant solution which shows the desired combinations of reverse transcriptase inhibitor (RTI) and protease inhibitor (PI) drug efficacies is achieved.
Positive Solution for the Elliptic Problems with Sublinear and Superlinear Nonlinearities
Authors: Yuan Chunmei , Guo Shujuan , Tong Kaiyu
Published: January 2011

This paper deals with the existence of positive solutions for the elliptic problems with sublinear and superlinear nonlinearities −Δu = λa(x)up + b(x)uq in Ω, u > 0 in Ω, u = 0 on ∂Ω, where λ > 0 is a real parameter, 0 < p < 1 < q. Ω is a bounded domain in ℝN   (N ≥ 3), and
a(x) and b(x) are some given functions. By means of variational method and super‐subsolution method, we obtain some results about existence of positive solutions.
Superconductivity due to Condensation of Monopoles around RCD Strings in SU(2) Gauge Theory
Authors: Rajput B. S. , Kumar Sandeep
Published: January 2011

The study of the condensation of monopoles and the resulting chromomagnetic superconductivity have been undertaken in restricted chromodynamics of SU(2) gauge theory. Constructing the RCD Lagrangian and the partition function for monopoles in terms of string action and the action of the current around the strings, the monopole current in RCD chromo magnetic superconductor has been derived and it has shown that in London′ limit the penetration length governs the monopole density around RCD string in chromo magnetic superconductors while with finite (nonzero) coherence length the leading behavior of the monopole density at large distances from the string is controlled by the coherence length and not by the penetration length.
Limitations of Online Information on Abdominal Aortic Aneurysm
Authors: Goldberg Carolyn G. , Berman Loren , Gusberg Richard J.
Published: January 2011

Background. Patients with AAA face a complex decision, and knowledge of the risks and benefits of each treatment option is essential to informed decision-making. Here we assess the current information on the internet accessible to patients regarding the management of AAA.Study Design. We performed a search on Google using the keywords “abdominal aortic aneurysm” and reviewed the top 50 web sites. We focused on information related to treatment options and alternatives to treatment and the risks of each option.Results. Twenty-seven websites were included in the study. Nearly 30% of websites discussed the risk of mortality and myocardial infarction after open surgery, compared to only 7.4% for both risks after EVAR. Other complications were listed by fewer websites. Fifty-five percent of websites reported that patients had a faster recovery following EVAR, but only 18.5% mentioned the risk of reintervention after EVAR or the need for long-term surveillance with CT scans.Conclusions. While most websites included descriptive information on AAA and mentioned the potential treatment options available to patients, the discussion of the risks of open surgery and EVAR was inadequate. These results suggest that websites frequently accessed by patients lack important information regarding surgical risk.
Attenuation of Brain Nitrostative and Oxidative Damage by Brain Cooling during Experimental Traumatic Brain Injury
Authors: Kuo Jinn-Rung , Lo Chong-Jeh , Chang Ching-Ping , Lin Mao- Tsun , Chio Chung-Ching
Published: January 2011

The aim of the present study was to ascertain whether brain cooling causes attenuation of traumatic brain injury by reducing brain nitrostative and oxidative damage. Brain cooling was accomplished by infusion of 5 mL of 4°C saline over 5 minutes via the external jugular vein. Immediately after the onset of traumatic brain injury, rats were randomized into two groups and given 37°C or 4°C normal saline. Another group of rats were used as sham operated controls. Behavioral and biochemical assessments were conducted on 72 hours after brain injury or sham operation. As compared to those of the sham‐operated controls, the 37°C saline‐treated brain injured animals displayed motor deficits, higher cerebral contusion volume and incidence, higher oxidative damage (e.g., lower values of cerebral superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, but higher values of cerebral malondialdehyde), and higher nitrostative damage (e.g., higher values of neuronal nitric oxide synthase and 3‐nitrotyrosine). All the motor deficits and brain nitrostative and oxidative damage were significantly reduced by retrograde perfusion of 4°C saline via the jugular vein. Our data suggest that brain cooling may improve the outcomes of traumatic brain injury in rats by reducing brain nitrostative and oxidative damage.
Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic
Authors: Shanker Manish , Jin Jiankang , Branch Cynthia D. , Miyamoto Shinya , Grimm Elizabeth A. , Roth Jack A. , Ramesh Rajagopal
Published: January 2011

Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.
The Effect of IntelliDrive on the Efficiency of Highway Transportation Systems
Authors: Nekoui Mohammad , Pishro-Nik Hossein , Ni Daiheng
Published: January 2011

Recently, the IntelliDrive initiative has been proposed by the US Department of Transportation (USDOT)
to enhance on-road safety and efficiency. In this study, we provide a mathematical framework which predicts the effect of such technologies on the efficiency of multilane highway systems prior to their real-life deployment. Our study shall encompass mixed traffic conditions in which a variety of assisted, automated and unequipped vehicles coexist. We show that intervehicular communications improves the flow of vehicles by reducing the perception-reaction (P-R) times of drivers and, in some cases, allowing for more efficient lane-changing operations. As we shall see, unlike the latter, the former effect of IntelliDrive on driver P-R time is always there, regardless of the specific traffic conditions.
Strong Convergence of Modified Halpern Iterations in CAT(0) Spaces
Authors: Cuntavepanit A , Panyanak B
Published: January 2011

Strong convergence theorems are established for the modified Halpern iterations of nonexpansive mappings in CAT(0) spaces. Our results extend and improve the recent ones announced by Kim and Xu (2005), Hu (2008), Song and Chen (2008), Saejung (2010), and many others.
Male Bias in the Song Control System despite Female Bias in Song Rate in Streak-Backed Orioles (Icterus pustulatus)
Authors: Hall Zachary J. , MacDougall-Shackleton Scott A. , Osorio-Beristain Marcela , Murphy Troy G.
Published: January 2011

The song control system is a group of discrete interconnected nuclei found in the brains of all songbirds (suborder Passeri). Previous studies have reported a positive relationship between sex differences in song nucleus volumes and sex differences in song behavior across numerous songbird species, with species exhibiting greater sex differences in behavior also exhibiting greater sex differences in the brain. This body of comparative research, however, has failed to incorporate data from a bird species in which females sing more than males. In this study, we examine song nucleus volumes in both sexes of the streak-backed oriole (Icterus pustulatus), a New World blackbird with a female bias in song rate and similar song complexity between the sexes. Results from this neuroanatomical analysis are contrary to what was to be expected from previous research: despite the female bias in song rate, males have a significantly larger HVC and area X song nucleus volumes. Specifically, male HVC was 75% larger than that of females, and male area X was 64% larger than that of females. There was no significant sex difference in the size of the nucleus robustus arcopallialis. The lack of a positive relationship between song nuclei and singing behavior in these orioles demonstrates that our current understanding of song modulation via the song control system may be overly reliant on basic measures such as total volumes.
Virtual Reconstructions of the Endocranial Cavity of Rhea americana (Aves, Palaeognathae): Postnatal Anatomical Changes
Authors: Picasso Mariana B.J. , Tambussi Claudia P. , Degrange Federico J.
Published: January 2011

We examined the external anatomy of the endocast of the Greater Rhea (Rhea americana, Palaeognathae), during 3 main stages of its postnatal life, and compared it with information available on other palaeognathous birds. Series of scans with spiral computed tomographies were obtained from 3 skulls of different ages (chick, juvenile and adult) of R. americana; digital 3-dimensional reconstruction was performed and brain volumes were calculated from the models obtained. Qualitative assessment of the brain anatomy of R. americana indicates a conical and ventrally located bulbus olfactorius, laterally expanded hemispherium telencephali, well-developed eminentia sagittalis, and conspicuous cerebellum and tectum mesencephali. Anatomy of the chick brain was markedly different: less lateral expansion of the hemispherium telencephali, and lesser development of the eminentia sagittalis and auricula cerebelli. Little change between chicks and adults was observed in some brain regions such as the tectum mesencephali, while the eminentia sagittalis showed great increase in size. The large size of the eminentia sagittalis coupled with its increasing development during ontogeny could reflect its importance for visual processing functions and the way these improve during growth. Finally, the brain of R. americana is similar to that of Struthio and Dromaius, but differs from that of the Tinamidae and of Apteryx, allowing recognition of 3 distinct brain morphologies among the Palaeognathae.
Induction Chemotherapy with Docetaxel/Cisplatin/5-Fluorouracil for Patients with Node-Positive Esophageal Cancer
Authors: Watanabe Masayuki , Nagai Yohei , Kinoshita Kuichi , Saito Seiya , Kurashige Junji , Karashima Ryuichi , Hirashima Kotaro , Sato Nobutaka , Imamura Yu , Hiyoshi Yukiharu , Baba Yoshifumi , Iwagami Shiro , Miyamoto Yuji , Iwatsuki Masaaki , Hayashi Naoko , Baba Hideo
Published: January 2011

Background: Despite improvements in the surgical management of esophageal cancer, the prognosis of patients with lymph node metastases is still unsatisfactory. Recently, survival benefit of neoadjuvant or induction chemotherapy for patients with esophageal cancer has been highlighted. Methods: Efficacy and toxicity of induction chemotherapy for esophageal cancer were reviewed. In addition, our experience on modified docetaxel/cisplatin/5-FU (DCF) as induction chemotherapy was also demonstrated. The modified DCF consisted of 60 mg/m2 of docetaxel on day 1, and 350 mg/m2 of 5-FU and 6 mg/m2 of cisplatin on days 1–5. Two courses have been administered as induction chemotherapy in 51 patients with node-positive esophageal cancer. Response was evaluated by RECIST v1.0 and changes in standardized uptake value by 18F-fluorodeoxyglucose positron emission tomography. Results: Induction chemotherapy may be beneficial for node-positive esophageal cancer, although the consensus has not yet been established. A regimen of induction chemotherapy should have a high response rate and cisplatin/5-FU may be underpowered as an induction setting. DCF can be a candidate for the regimen of induction chemotherapy for esophageal cancer, although severe adverse events have been reported. Several modified regimens to reduce the toxicity have been reported. The response rate of our series was 61% and a significant decrease in standardized uptake values was observed after the induction chemotherapy. Although high-grade neutropenia was still observed with this regimen, neither treatment-related death nor delay in the following treatment was observed. Conclusions: Modified DCF can be a regimen of induction chemotherapy for node-positive esophageal cancer because of its high efficacy, although an adequate care for severe neutropenia is needed.
Daikenchuto Ameliorates Muscle Hypercontractility in a Murine T-Cell-Mediated Persistent Gut Motor Dysfunction Model
Authors: Akiho Hirotada , Nakamura Kazuhiko
Published: January 2011

Background and Aims: Low-grade inflammation and immunological alterations are evident in functional gastrointestinal disorders such as irritable bowel syndrome (IBS). We evaluated the effects of daikenchuto (DKT), a pharmaceutical grade Japanese herbal medicine, on the hypercontractility of intestinal smooth muscle persisting after acute inflammation induced by a T-cell-activating anti-CD3 antibody (αCD3). Methods: BALB/c mice were injected with αCD3 (12.5 µg, i.p.), and DKT (2.7 g/kg) was administered orally once daily for 1 week. The contraction of isolated small intestinal muscle strips and muscle cells was examined on day 7 after αCD3 injection. The gene and protein expressions in the small intestines were evaluated by real-time PCR and multiplex immunoassays, respectively, on days 1, 3 and 7 after αCD3 injection. Results: αCD3 injection resulted in significant increases in carbachol-evoked contractility in the muscle strips and isolated smooth muscle cells on day 7. DKT ameliorated the αCD3-induced muscle hypercontractility on day 7 in both the muscle strips and smooth muscle cells. αCD3 injection rapidly up- and downregulated the mRNA and protein expressions of pro- and anti-inflammatory cytokines, respectively. Although the influence of DKT on the mRNA expressions was moderate, the protein expressions of IL-13 and IL-17 were significantly decreased. Conclusions: We observed changes in the intestinal muscle contractility in muscle strips and muscle cells following resolution of inflammation in a T-cell-mediated model of enteropathy. The observed modulation of cytokine expression and function by DKT may lead to the development of new pharmacotherapeutic strategies aimed at a wide variety of gut motor dysfunction disorders.
Usefulness of Magnifying Narrow-Band Imaging Endoscopy in the Helicobacter pylori-Related Chronic Gastritis
Authors: Okubo Masaaki , Tahara Tomomitsu , Shibata Tomoyuki , Nakamura Masakatsu , Kamiya Yoshio , Yoshioka Daisuke , Maeda Yoshiteru , Yonemura Joh , Ishizuka Takamitsu , Arisawa Tomiyasu , Hirata Ichiro
Published: January 2011

Combining the narrow-band imaging (NBI) system and magnifying endoscopy allows simple and clear visualization of microscopic structures of the superficial mucosa and its capillary patterns, which may be useful for precise endoscopic diagnosis in the gastrointestinal tract, being more closely to histopathological diagnosis. In the non-neoplastic gastric mucosa, there have been reports showing a potential usefulness of magnifying NBI for the diagnosis of Helicobacter pylori infection, degree of histological gastritis, and intestinal metaplasia. We have shown that magnifying NBI appearances in the non-neoplastic gastric mucosa also predicts pepsinogen levels, which indicates extension of gastric atrophy in the entire stomach, and gastric cancer occurrence. Furthermore, we have shown that magnifying NBI appearances predicts the result of H. pylori treatment. Clear visualization of fine mucosal and capillary patterns, obtained by magnifying NBI, allows prediction of the histological condition, more in detail without biopsy, and it may also be useful for less invasive, and cost-effective endoscopic gastric cancer surveillance, and prediction of H. pylori eradication.
Current Status of Narrow-Band Imaging Magnifying Colonoscopy for Colorectal Neoplasia in Japan
Authors: Oba S. , Tanaka S. , Sano Y. , Oka S. , Chayama K.
Published: January 2011

The narrow-band imaging system can be used to examine the microvascular architecture and surface pattern on the mucosal surface with high sensitivity. The clinical significance of NBI observation is summarized as follows: (1) differential diagnosis of hyperplasia, adenoma, and carcinoma; (2) diagnosis according to the presence of a surface pattern as an alternative to magnifying endoscopic observation with dye spraying, and (3) determination of the invasion depth of an early colorectal carcinoma. However, at present, many NBI magnifying observation classifications for colorectal tumor exist in Japan. To internationally standardize the NBI observation criteria, a simple classification system is required. On the basis of these backgrounds, an international cooperative group (Colon Tumor NBI Interest Group – CTNIG) has developed a simple category classification (NICE classification: NBI International Colorectal Endoscopic Classification) which classifies NBI findings into types 1–3.
Immunohistochemical Analysis of REG Iα Expression in Ulcerative Colitis-Associated Neoplastic Lesions
Authors: Tanaka Hiroyuki , Fukui Hirokazu , Fujii Shigehiko , Sekikawa Akira , Yamagishi Hidetsugu , Ichikawa Kazuhito , Tomita Shigeki , Imura Johji , Yasuda Yoshikazu , Chiba Tsutomu , Fujimori Takahiro
Published: January 2011

Background and Aims: The regenerating gene (REG)Iα has been identified by microarray analysis as a gene that is distinctly overexpressed in ulcerative colitis (UC), and its protein product is suggested to play a pivotal role in the development of UC-associated carcinoma. In the present study, we investigated the significance of REG Iα expression as a diagnostic marker of UC-associated neoplasia. Methods: Tissue samples were obtained from colectomy specimens from 31 patients with long-standing UC (mean disease duration 17.2 years, range 5–29). The lesions were evaluated according to the International Classification for Dysplasia in Inflammatory Bowel Diseases, and the sections were examined using immunohistochemistry for REG Iα and p53. Results: In the ‘regenerating atypia’ group, REG Iα immunoreactivity was restricted to the lower third of the UC mucosa (grade 1). Lesions classified as ‘indefinite for dysplasia’ also showed predominantly basal-type staining for REG Iα. However, in ‘low-grade dysplasia’ and ‘high-grade dysplasia’ lesions, the localization of REG Iα immunoreactivity expanded to the middle (grade 2) and upper (grade 3) third of the UC mucosa, respectively. The REG Iα immunostaining pattern differed significantly (p < 0.0001) between non-neoplastic and neoplastic lesions, and was significantly (p < 0.0001) associated with p53 overexpression. Conclusions: Immunohistochemical analysis of REG Iα expression is useful for differential diagnosis of non-neoplastic and neoplastic lesions in UC tissues.
FGF19 Protects Colonic Epithelial Cells against Hydrogen Peroxide
Authors: Uchiyama Kazuhiko , Naito Yuji , Takagi Tomohisa , Mizushima Katsura , Hayashi Natsuko , Handa Osamu , Ishikawa Takeshi , Yagi Nobuaki , Kokura Satoshi , Yoshikawa Toshikazu
Published: January 2011

Background/Aims: The apoptosis induced by hydrogen peroxide (H2O2) in colonic epithelial cells is very important for the pathogenesis of inflammatory bowel disease (IBD). Fibroblast growth factor (FGF) 15, the human ortholog of FGF19, is reported to be secreted from colonic myofibroblasts and enhances colonic epithelial restitution, but little is known about the function of FGF19 to colonic epithelial cells. In the present study, we investigate the anti-apoptosis effect of FGF19 in colonic epithelial cells treated with H2O2. Methods: Young adult mouse colonic epithelial (YAMC) cells are used to investigate the protective role of FGF19. Cellular viability was determined by WST-8 assay, and apoptosis was measured by Hoechst staining and Western blotting of cleaved caspase-3. YAMC cells were pretreated by FGF19 and H2O2 was used for cellular damage. Results: We demonstrated that pretreatment of FGF19 (50 ng/ml) significantly protects YAMC cells treated with H2O2 assessed by WST-8. We also demonstrated Hoechst staining of YAMC cells and that H2O2-induced apoptosis is significantly reduced by FGF19 treatment via inhibition of the caspase-3 pathway. Conclusion: These results indicate FGF19 protects YAMC cells against H2O2 and might be related to the pathogenesis of IBD. Even further studies are needed – FGF19 may be one of the possible therapeutic strategies of IBD.
Visceral Obesity and the Risk of Barrett’s Esophagus
Authors: Akiyama Tomoyuki , Yoneda Masato , Maeda Shin , Nakajima Atsushi , Koyama Shigeru , Inamori Masahiko
Published: January 2011

It still remains controversial whether simple obesity, as measured by the body mass index (BMI), is an independent risk factor for Barrett’s esophagus (BE). Recent studies have shown abdominal obesity, as defined by the waist circumference (WC) and the waist-to-hip ratio (WHR), to be a risk factor for BE, independent of the BMI, with the association between BMI and BE being no longer observed after adjustment for the WC and WHR. Moreover, visceral obesity, as directly measured by the surface area of the visceral adipose tissue (VAT) on abdominal CT images, has also been reported to have an association with the risk of BE. In addition to the mechanical effects of abdominal obesity, that is, increase of the intra- abdominal pressure by the large amount of adipose tissue, circulating factors secreted from the VAT, such as tumor necrosis factor-α, interleukin-6, leptin, and adiponectin, have also been proposed to be pathogenetically linked to BE and esophageal adenocarcinoma. Obesity is associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal obesity, especially visceral obesity. This raises several questions regarding the pathogenesis of obesity-related BE. Larger studies with prospective enrollment of patients are required for further examination of this issue.
Antibiotic Combination Therapy for Steroid Withdrawal in Steroid-Dependent Ulcerative Colitis
Authors: Terao Shuichi , Yamashiro Kenzo , Tamura Isamu , Hirano Takahiro , Ohkusa Toshifumi , Kato Kimitoshi
Published: January 2011

Background and Aim: Immunosuppressive drugs are recommended for use as replacements of steroid therapy in sustaining remission of steroid-dependent ulcerative colitis (UC). However, discontinuation of these therapeutic agents leads to a high relapse, and their long-term administration has not been proven safe. A newly introduced antibiotic combination therapy led to improvement and remission of active UC. The aim of this study is to examine whether this new therapy can replace immunosuppressive agents and allow discontinuation of steroids in steroid-dependent UC remission. Methods: 48 patients with steroid-dependent UC were recruited for a 2-week treatment with amoxicillin, tetracycline, and metronidazole (ATM). Examination of clinical symptoms, endoscopy, and histological evaluation were performed before and 6 and 12 months after treatment. Results: The proportion of patients who showed clinical improvement at 6 and 12 months after treatment was 54.2% (26/48) and 75.0% (36/48), respectively. The rate of clinical remission at 6 and 12 months was 31.3% (15/48) and 37.5% (18/48), respectively. Steroid withdrawal was attained in 64.6% (31/48) and 70.8% (34/48) of patients at 6 and 12 months, respectively. Endoscopic improvement was detected in 56.3% (27/48), and histological improvement was detected in 52.1% (25/48) at the final observation point for each patient. Conclusion: The triple antibiotic therapy resulted in improvement, remission, and steroid withdrawal in steroid-dependent UC patients.
Gastrointestinal Bleeding after Percutaneous Coronary Intervention
Authors: Tanigawa Tetsuya , Watanabe Toshio , Nadatani Yuji , Otani Koji , Machida Hirohisa , Okazaki Hirotoshi , Yamagami Hirokazu , Watanabe Kenji , Tominaga Kazunari , Fujiwara Yasuhiro , Arakawa Tetsuo
Published: January 2011

Percutaneous coronary intervention (PCI) is now performed in a wide range of patients with coronary artery disease. Complications of PCI include in-stent re-stenosis and in-stent thrombosis. According to the recent 2005 guidelines of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions, dual antiplatelet therapy with low-dose aspirin and thienopyridine derivatives such as ticlopidine and clopidogrel should be used in patients who have undergone PCI. A serious complication of dual antiplatelet therapy is bleeding, most of which arise from the gastrointestinal (GI) tract. In this article we review published studies about GI bleeding in patients who have undergone PCI. The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization and cost. Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI. Recent clinical and experimental studies indicate that administration of low-dose aspirin may also increase the risk of adverse events in the small intestine. Although some prophylactic strategies such as proton-pump inhibitor, H2 receptor antagonist and eradication of Helicobacter pylori are proposed, there are few randomized controlled trials assessing the best strategy for the prevention of GI bleeding after PCI. Further extensive studies are required to ascertain the beneficial effect of prophylactic agents for dual antiplatelet therapy following PCI.
Clinical Outcome and Clinicopathological Characteristics of Recurrence after Laparoscopic Gastrectomy for Advanced Gastric Cancer
Authors: Yoshimura Fumihiro , Inaba Kazuki , Kawamura Yuichiro , Ishida Yoshinori , Taniguchi Keizo , Isogaki Jun , Satoh Seiji , Kanaya Seiichiro , Sakurai Yoichi , Uyama Ichiro
Published: January 2011

Background: Although laparoscopic gastrectomy has been recognized as a treatment of early gastric cancer, the indication for laparoscopic gastrectomy with D2 lymph node dissection has remained controversial. D2 lymph node dissection is considered to be feasible for advanced gastric cancer in some high-volume institutions specifically trained for the laparoscopic procedure. This study was undertaken to determine the clinical outcome and clinicopathological characteristics of patients who showed recurrence following laparoscopic gastrectomy for advanced gastric cancer. Methods: From August 1999 through February 2009, among 805 patients who underwent laparoscopic gastrectomy associated with regional lymph node dissection, a total of 209 patients undergoing gastrectomy associated with lymph node dissection who consequently obtained complete resection for advanced gastric cancer were subjected to the retrospective analysis to evaluate clinical outcome. Results: The mean period of postoperative observation was 1,068 days. The final stages of the 209 cases were as follows: 83 in IB, 56 in II, 46 in IIIA, and 24 in IIIB. The 5-year survival rate was 89.1% in stage IB, 93.1% in stage II, 52.5% in stage IIIA, and 46.5% in stage IIIB, respectively. A total of 27 patients (12.9%) had recurrence. Postoperative recurrence of gastric carcinoma occurred in peritoneal dissemination in 13 patients, liver in 7, distant lymph nodes in 6, ovary in 3, lung in 2, skin in 1, and meninges in 1 patient. There were neither port-site metastases nor locoregional recurrence. Conclusion: The characteristics and the rate of postoperative recurrence after laparoscopic gastrectomy for advanced gastric cancer were not greatly different from those of the open conventional procedure. Although further observation is required to finally conclude long-term survival, laparoscopic radical gastrectomy may possibly be indicated for patients with advanced gastric cancer.
A Reduced Progenitor Pool Population Accounts for the Rudimentary Appearance of the Septum, Medial Pallium and Dorsal Pallium in Birds
Authors: Charvet Christine J.
Published: January 2011

To date, most studies comparing birds and mammals have focused on the similarities in brain development, architecture and connectivity. However, major differences in size, anatomy and organization exist in the telencephalon of adult birds and mammals. For instance, the septum, medial pallium and dorsal pallium of birds appear rudimentary compared with those of mammals. To identify the developmental processes that give rise to this difference in size and anatomy of the septum, medial pallium and dorsal pallium, the thickness of the ventricular zone that encompasses these regions was measured in embryonic birds (i.e. chickens, sparrows) and mammals (i.e. rabbits, hedgehogs, shrews, platypus). Cumulative bromodeoxyuridine (BrdU) labeling in chickens at embryonic day 7 and 8 was also used to examine levels of cell proliferation in the ventricular zone of the septum, medial pallium and dorsal pallium. The study’s main finding is that the ventricular zone of the septum, medial pallium and dorsal pallium is thinner in birds than in mammals. In chickens, the septum, medial pallium and dorsal pallium ventricular zone harbor few proliferating (i.e. BrdU+) cells. Collectively, these findings suggest that a reduced progenitor pool population account for the ‘rudimentary’ appearance of the avian septum, medial pallium and dorsal pallium.
The Mitochondrial Connection in Auditory Neuropathy
Authors: Cacace Anthony T. , Pinheiro Joaquim M.B.
Published: January 2011

‘Auditory neuropathy’ (AN), the term used to codify a primary degeneration of the auditory nerve, can be linked directly or indirectly to mitochondrial dysfunction. These observations are based on the expression of AN in known mitochondrial-based neurological diseases (Friedreich’s ataxia, Mohr-Tranebjærg syndrome), in conditions where defects in axonal transport, protein trafficking, and fusion processes perturb and/or disrupt mitochondrial dynamics (Charcot-Marie-Tooth disease, autosomal dominant optic atrophy), in a common neonatal condition known to be toxic to mitochondria (hyperbilirubinemia), and where respiratory chain deficiencies produce reductions in oxidative phosphorylation that adversely affect peripheral auditory mechanisms. This body of evidence is solidified by data derived from temporal bone and genetic studies, biochemical, molecular biologic, behavioral, electroacoustic, and electrophysiological investigations.
Maxillary Dental Arch Dimensions in 6-Year-Old Children with Articulatory Speech Disorders
Authors: Heliövaara Arja
Published: January 2011

Aims: To evaluate maxillary dental arch dimensions in 6-year-old children with articulatory speech disorders and to compare their dental arch dimensions with age- and sex-matched controls without speech disorders. Methods: Fifty-two children (15 girls) with errors in the articulation of the sounds /r/, /s/ or /l/ were compared retrospectively with age- and sex-matched controls from dental casts taken at a mean age of 6.4 years (range 5.0–8.4). All children with articulatory speech disorders had been referred to City of Helsinki Health Care, Dental Care Department by a phoniatrician or a speech therapist in order to get oral-motor activators (removable palatal plates) to be used in their speech therapy. A χ2-test and paired Student’s t tests were used in the statistical analyses. Results: The children with articulatory speech disorders had similar maxillary dental arch widths but smaller maxillary dental arch length than the controls. Conclusion: This small series suggests that 6-year-old children with articulatory speech disorders may have decreased maxillary dental arch length.
Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer’s Disease
Authors: Leyhe Thomas , Saur Ralf , Eschweiler Gerhard W. , Milian Monika
Published: January 2011

Background/Aims: Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods: We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer’s disease (EAD). Results: The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions: Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.
Sublexical Properties of Spoken Words Modulate Activity in Broca's Area but Not Superior Temporal Cortex: Implications for Models of Speech Recognition
Authors: Vaden Kenneth I. , Piquado Tepring , Hickok Gregory
Published: January 2011

Many models of spoken word recognition posit that the acoustic stream is parsed into phoneme level units, which in turn activate larger representations [McClelland, J. L., & Elman, J. L. The TRACE model of speech perception. Cognitive Psychology, 18, 1–86, 1986], whereas others suggest that larger units of analysis are activated without the need for segmental mediation [Greenberg, S. A multitier theoretical framework for understanding spoken language. In S. Greenberg & W. A. Ainsworth (Eds.), Listening to speech: An auditory perspective (pp. 411–433). Mahwah, NJ: Erlbaum, 2005; Klatt, D. H. Speech perception: A model of acoustic-phonetic analysis and lexical access. Journal of Phonetics, 7, 279–312, 1979; Massaro, D. W. Preperceptual images, processing time, and perceptual units in auditory perception. Psychological Review, 79, 124–145, 1972]. Identifying segmental effects in the brain's response to speech may speak to this question. For example, if such effects were localized to relatively early processing stages in auditory cortex, this would support a model of speech recognition in which segmental units are explicitly parsed out. In contrast, segmental processes that occur outside auditory cortex may indicate that alternative models should be considered. The current fMRI experiment manipulated the phonotactic frequency (PF) of words that were auditorily presented in short lists while participants performed a pseudoword detection task. PF is thought to modulate networks in which phoneme level units are represented. The present experiment identified activity in the left inferior frontal gyrus that was positively correlated with PF. No effects of PF were found in temporal lobe regions. We propose that the observed phonotactic effects during speech listening reflect the strength of the association between acoustic speech patterns and articulatory speech codes involving phoneme level units. On the basis of existing lesion evidence, we interpret the function of this auditory–motor association as playing a role primarily in production. These findings are consistent with the view that phoneme level units are not necessarily accessed during speech recognition.