bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studies
Authors: Manjappa A.S. , Nanjwade Basavaraj K. , Manvi F.V. , Murthy R.S.R. 
Published: July 2009

AbstractMost ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol‐to‐gel transition in the cul‐de‐sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti‐inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH‐triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E15LV), which acted as a viscosity enhancer. The prepared formulations were characterized for clarity, pH, drug content, rheology, and in vivo drug release. Clarity, pH, and drug content of the developed formulations were found to be satisfactory. The developed formulation showed pseudo‐plastic rheology. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also importantly is the ease of instillation afforded and decreased frequency of instillation resulting in better patient acceptance. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.
Development and use of methylnaltrexone, a peripherally acting opioid antagonist, to treat side effects related to opioid use
Authors: Yuan Chun‐Su , Foss Joseph F. , Williams Wade A. , Moss Jonathan 
Published: July 2009

AbstractOpioid medications are used extensively as potent analgesics for treating moderate to severe pain. Although opioids offer reliable pain relief, their use is associated with a number of adverse effects, especially constipation. Conventional measures for ameliorating opioid‐induced adverse effects are often insufficient. Thus, reducing the severity of these adverse effects is of utmost importance for patients who require the benefits of opioid analgesics. Since opioids mediate pain‐relieving and adverse effects through the same classes of receptors, i.e.,mu,delta, andkappa, it has been challenging to dissociate beneficial effects from detrimental ones. Methylnaltrexone is the first peripherally acting opioid receptor antagonist to receive FDA approval. This compound offers the therapeutic potential to block or reverse the undesired side effects of opioids that are mediated by receptors located in the periphery (e.g., in the gastrointestinal tract), without affecting analgesia or precipitating opioid withdrawal symptoms, which are mediated predominantly by receptors in the central nervous system. This review provides a history of the development of methylnaltrexone, discusses studies that relate to opioid bowel dysfunction, and explores other uses of this compound. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.
Particle tracking model of electrophoretic morphogen movement reveals stochastic dynamics of embryonic gradient
Authors: Zhang Ying , Levin Michael 
Published: July 2009

AbstractSome developmental events rely on an electrophoretic force to produce morphogenetic gradients. To quantitatively explore the dynamics of this process, we constructed a stochastic model of an early phase of left–right patterning: serotonin movement through the gap junction‐coupled blastomeres of the Xenopus embryo. Particle‐tracking simulations showed that a left–right gradient is formed rapidly, quickly reaching a final stable level. The voltage difference was critical for producing a morphogen gradient of the right steepness; gap junctional connectivity and morphogen mass determined the timing of the gradient. Endogenous electrophoresis drives ∼50% of the particles across more than one cell width, and ∼20% can travel across half the embryo. The stochastic behavior of the resulting gradients exhibited unexpected complexity among blastomeres' morphogen content, and showed how spatiotemporal variability within individual cells resulted in robust and consistent gradients across the embryonic left–right axis. Analysis of the distribution profile of gradient gain values made quantitative predictions about the conditions that result in the observed background level of laterality defects in unperturbed frog embryos. This work provides a general model that can be used to quantitatively analyze the unexpectedly complex dynamics of morphogens in a wide variety of systems. Developmental Dynamics 238:1923–1935, 2009. © 2009 Wiley‐Liss, Inc.
Mathematical modeling of the capillary‐like pattern generated by adrenomedullin‐treated human vascular endothelial cells in vitro
Authors: Guidolin Diego , Albertin Giovanna , Sorato Elisa , Oselladore Barbara , Mascarin Alessandra , Ribatti Domenico 
Published: July 2009

AbstractA recently proposed approach was used to model the self‐organization into capillary‐like structures of human vascular endothelial cells cultured on Matrigel. The model combines a Cellular Potts Model, considering cell adhesion, cytoskeletal rearrangement and chemotaxis, and a Partial Differential Equation model describing the release and the diffusion of a chemoattractant. The results were compared with the data from real in vitro experiments to establish the capability of the model to accurately reproduce both the spontaneous self‐assembly of unstimulated cells and their self‐organization in the presence of the pro‐angiogenic factor adrenomedullin. The results showed that the model can accurately reproduce the self‐assembly of unstimulated cells, but it failed in reproducing the adrenomedullin‐induced self‐organization of the cells. The extension of the model to include cell proliferation led to a good match between simulated and experimental patterns in both cases with predicted proliferation rates in agreement with the data of cell proliferation experiments. Developmental Dynamics 238:1951–1963, 2009. © 2009 Wiley‐Liss, Inc.
Development of the neuromuscular system during asexual propagation in an invertebrate chordate
Authors: Tiozzo Stefano , Murray Maureen , Degnan Bernard M. , De Tomaso Anthony W. , Croll Roger P. 
Published: July 2009

AbstractBotryllus schlosseri is a colonial ascidian, and the closest relative to vertebrates that can completely regenerate its entire body, including all somatic and germline tissues, using an asexual developmental pathway called blastogenesis. This regenerative potential exhibited by Botryllus and other colonial ascidians does not exist in any other chordate and makes B. schlosseri a promising model to investigate the cellular and molecular basis of regeneration. In this report, we describe postembryonic myogenesis and characterized the development of the neural system during blastogenic development. α‐Tubulin immunoreactivity revealed a high correlation with previous studies on the motor nervous system. The pattern of the serotoninergic system in the adult reflects that observed in solitary ascidians, but in early blastogenesis suggests a morphogenic role of this monoamine. In summary, this study provides the morphological framework to dissect the mechanisms underlying the ability to regenerate entire organ systems as an adult in a chordate model. Developmental Dynamics 238:2081–2094, 2009. © 2009 Wiley‐Liss, Inc.
Male‐specific expression of Aldh1a1 in mouse and chicken fetal testes: Implications for retinoid balance in gonad development
Authors: Bowles Josephine , Feng Chun‐Wei , Knight Deon , Smith Craig A. , Roeszler Kelly N. , Bagheri‐Fam Stefan , Harley Vincent R. , Sinclair Andrew H. , Koopman Peter 
Published: July 2009

AbstractBalanced production and degradation of retinoids is important in regulating development of several organ systems in the vertebrate embryo. Among these, it is known that retinoic acid (RA), and the retinoid‐catabolyzing enzyme CYP26B1 together regulate the sex‐specific behavior of germ cells in developing mouse gonads. We report here that the gene encoding a cytosolic class‐1 aldehyde dehydrogenase, ALDH1A1, a weak catalyst of RA production, is strongly expressed in a male‐specific manner in somatic cells of the developing mouse testis, beginning shortly after Sry expression is first detectable. This expression pattern is conserved in the developing male gonad of the chicken and is dependent on the testis‐specific transcription factor SOX9. Our data suggest that low levels of RA may be required for early developmental events in the testis, or that Aldh1a1 expression in the fetus may prefigure a later requirement for ALDH1A1 in regulating spermatogenesis postnatally. Developmental Dynamics 238:2073–2080, 2009. © 2009 Wiley‐Liss, Inc.
High resolution map of Caenorhabditis elegans gap junction proteins
Authors: Altun Zeynep F. , Chen Bojun , Wang Zhao‐Weng , Hall David H. 
Published: July 2009

AbstractThe innexin family of gap junction proteins has 25 members in Caenorhabditis elegans. Here, we describe the first high‐resolution expression map of all members through analysis of live worms transformed with green fluorescent protein under the control of entire promoter regions. Our analyses show that innexins have dynamic expression patterns throughout development and are found in virtually all cell types and tissues. Complex tissues, such as the pharynx, intestine, gonad, as well as scaffolding tissues and guidepost cells express a variety of innexins in overlapping or complementary patterns, suggesting they may form heteromeric and heterotypic channels. Innexin expression occurs in several types of cells that are not known to form gap junctions as well as in a pair of migrating cells, suggesting they may have hemichannel function. Therefore, innexins likely play roles in almost all body functions, including embryonic development, cell fate determination, oogenesis, egg laying, pharyngeal pumping, excretion, and locomotion. Developmental Dynamics 238:1936–1950, 2009. © 2009 Wiley‐Liss, Inc.
Unified description of regeneration by coupled dynamical systems theory: Intercalary/segmented regeneration in insect legs
Authors: Yoshida Hiroshi , Kaneko Kunihiko 
Published: July 2009

AbstractRegeneration phenomena are ubiquitous in nature and are studied in a variety of experiments. Positional information and feedback‐loop hierarchy are theories that have been proposed to explain ordering rules in regeneration; however, some regeneration phenomena violate the rules derived from them. In particular, grafted junction stumps with the same value/hierarchy sometimes lead to one extra segmented portion, termed segmented regeneration. To present a unified description of all insect leg regeneration phenomena, we propose a theoretical mechanism for regeneration without postulating positional information, by using a model that consists of intracellular reaction dynamics of chemical concentrations, cell‐to‐cell interactions, and an increase in cell number. As a normal developmental process, successive differentiation from pluripotent cells appears, as described by transition from cells with intracellular chaotic dynamics to those with oscillatory or fixed‐point dynamics. By assigning chaotic and nonchaotic cell types to corresponding positions instead of positional information, intercalary, segmented, and tarsus regeneration are explained coherently. With this assignment of pluripotency to chaotic dynamics, a unified description of regeneration is obtained with some predictive value for new experiments. Developmental Dynamics 238:1974–1983, 2009. © 2009 Wiley‐Liss, Inc.
Porcine pluripotency cell signaling develops from the inner cell mass to the epiblast during early development
Authors: Hall Vanessa J. , Christensen Josef , Gao Yu , Schmidt Mette H. , Hyttel Poul 
Published: July 2009

AbstractThe signaling mechanisms regulating pluripotency in porcine embryonic stem cells and embryos are unknown. In this study, we characterize cell signaling in the in‐vivo porcine inner cell mass and later‐stage epiblast. We evaluate expression of OCT4, NANOG, SOX2, genes within the JAK/STAT pathway (LIF, LIFR, GP130), FGF pathway (bFGF, FGFR1, FGFR2), BMP pathway (BMP4), and downstream‐activated genes (STAT3, c‐Myc, c‐Fos, and SMAD4). We discovered two different expression profiles exist in the developing porcine embryo. The D6 porcine blastocyst (inner cell mass stage) is devoid in the expression of most genes analyzed, with the exception of OCT4. In contrast, the D11 epiblast expressed 10 of the 12 genes investigated. Immunocytochemistry confirmed LIFR and bFGF was not expressed in the epiblast, but within the trophectoderm. These findings reveal cell signaling associated with maintaining pluripotency in human embryonic stem cells is detectable in the porcine epiblast, but not in the inner cell mass. Developmental Dynamics 238:2014–2024, 2009. © 2009 Wiley‐Liss, Inc.
Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography
Authors: Biehl Jesse K. , Yamanaka Satoshi , Desai Tejal A. , Boheler Kenneth R. , Russell Brenda 
Published: July 2009

AbstractThe niche in which stem cells reside and differentiate is a complex physicochemical microenvironment that regulates cell function. The role played by three‐dimensional physical contours was studied on cell progeny derived from mouse embryonic stem cells using microtopographies created on PDMS (poly‐dimethyl‐siloxane) membranes. While markers of differentiation were not affected, the proliferation of heterogeneous mouse embryonic stem cell‐derived progeny was attenuated by 15 μm‐, but not 5 μm‐high microprojections. This reduction was reversed by Rho kinase and myosin light chain kinase inhibition, which diminishes the tension generating ability of stress fibers. Purified cardiomyocytes derived from embryonic stem cells also showed significant blunting of proliferation and increased beating rates compared with cells grown on flat substrates. Thus, proliferation of stem cell‐derived progeny appears to be regulated by microtopography through tension‐generation of contractility in the third‐dimension. These results emphasize the importance of topographic cues in the modulation of stem cell progeny behavior. Developmental Dynamics 238:1964–1973, 2009. © 2009 Wiley‐Liss, Inc.
Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung
Authors: Abler Lisa L. , Mansour Suzanne L. , Sun Xin 
Published: July 2009

AbstractFibroblast growth factor 10 (FGF10) signaling through FGF receptor 2 (FGFR2) is required for lung initiation. While studies indicate that Fgf10 and Fgfr2 are also important at later stages of lung development, their roles in early branching events remain unclear. We addressed this question through conditional inactivation of both genes in mouse subsequent to lung initiation. Inactivation of Fgf10 in lung mesenchyme resulted in smaller lobes with a reduced number of branches. Inactivation of Fgfr2 in lung epithelium resulted in disruption of lobes and small epithelial outgrowths that arose arbitrarily along the main bronchi. In both mutants, there was an increase in cell death. Also, the expression patterns of key signaling molecules implicated in branching morphogenesis were altered and a proximal lung marker was expanded distally. Our results indicate that both Fgf10 and Fgfr2 are required for a normal branching program and for proper proximal–distal patterning of the lung.Developmental Dynamics 238:1999–2013, 2009. © 2009 Wiley‐Liss, Inc.
Obesity: Is it a mental disorder?
Authors: Marcus Marsha D. , Wildes Jennifer E. 
Published: July 2009

AbstractObjective:Using Wakefield's conceptualization of mental disorder as “harmful mental dysfunction” (Wakefield, Am Psychol, 47, 373–388, 1992), we examined the evidence for including obesity as a mental disorder in DSM‐V.Method:We searched computer databases and examined reference lists from review articles published in the last 10 years to identify empirical papers relevant to the present review.Results:Obesity is a condition of heterogeneous etiology that is harmful for most individuals. However, there is scant evidence that obesity, in general, is caused by mental dysfunction. Although recent work examining the neurocircuitry of energy balance has suggested that mental dysfunction may be involved in the etiology of specific obesity phenotypes, findings are too preliminary to support classification of obesity as a mental disorder. Nevertheless, there is evidence that obesity is related to mental disorder and many of the medications used to treat psychiatric illness.Discussion:There is little evidence for including obesity as a mental disorder in DSM‐V. However, results confirm the importance of monitoring adiposity routinely among patients with psychiatric illness. © 2009 American Psychiatric Association. (Int J Eat Disord 2009)
Validity and utility of the current definition of binge eating
Authors: Wolfe Barbara E. , Baker Christina Wood , Smith Adrian T. , Kelly‐Weeder Susan 
Published: July 2009

AbstractObjectiveBinge eating, a cardinal symptom of bulimia nervosa (BN) and binge eating disorder (BED), continues to pose challenges in terms of its definition and thus construct validity and clinical utility. This article reviews the available empirical data that support or refute the current DSM‐IV‐TR defined characteristics of a binge episode.MethodA systematic literature review was conducted using Medline/PubMed electronic database on DSM‐IV‐TR defined binge characteristics and associated attributes.ResultsData support the current DSM guidelines indicating that binge episodes typically occur in less than 2 h. Size of binge episodes has variability across BN and BED diagnostic groups. Loss of control (LOC) continues to be a core feature of binge eating. Negative affect is the most widely reported antecedent. Strikingly, little is known about binge episodes among individuals with anorexia nervosa‐binge/purge subtype.DiscussionAvailable empirical evidence supports the current DSM duration and LOC attributes of a binge episode in BN and BED. However, a more controversial issues is the extent to which size is important in the definition of a binge episode (e.g., subjective vs. objective episodes) across diagnostic categories and the extent to which binge size informs prognosis, treatment, and clinical outcomes. Further study of binge eating attributes in AN is needed. © 2009 American Psychiatric Association. Int J Eat Disord 2009
Rapid release of cytoplasmic IL‐15 from tumor‐associated macrophages is an initial and critical event in IL‐12‐initiated tumor regression
Authors: Watkins Stephanie K. , Li Bing , Richardson Katharine S. , Head Kimberly , Egilmez Nejat K. , Zeng Qun , Suttles Jill , Stout Robert D. 
Published: July 2009

AbstractThis study reveals that the IL‐15 rapidly released into serum upon IL‐12 injection into tumor‐bearing mice is critical for the subsequent leukocytic infiltration of the tumor and tumor‐bearing tissue. The increase in serum IL‐15 occurs within 2 h after IL‐12 injection concomitantly with a decrease in cytoplasmic IL‐15 in tumor‐associated Mϕ (TAM). Injection of anti‐IL‐15 one hour prior to IL‐12 abrogates subsequent leukocytic infiltration into the tumor and prevents the IL‐12‐induced reduction of primary tumor mass and the clearance of metastases. Administration of anti‐IL‐15 18 h after IL‐12 did not have a detectable impact on IL‐12‐induced leukocytic infiltration of the tumor. Deletion of NK cells had no impact on the IL‐12‐induced change in the functional phenotype of TAM or on the subsequent initiation of leukocytic infiltration of the tumor. In concert with our previous studies demonstrating that IL‐12 reduces tumor‐supportive activities of TAM, the current study supports the hypothesis that functional re‐programming of TAM not only undermines Mϕ support for tumor growth but also contributes to a critical step in the initiation of anti‐tumor immune responses. In this context, the functional plasticity and pro‐immunogenic potential of TAM may constitute a significant and unappreciated target in existing cytokine therapies.
Strategies for optimizing targeting and delivery of mucosal HIV vaccines
Authors: Ahlers Jeffrey D. , Belyakov Igor M. 
Published: July 2009

AbstractEffective frontline defenses against HIV‐1 will require targeting vaccines to mucosal tissue in order to induce αβ CD8+ lymphocytes in mucosal effector sites (lamina propria and intraepithelial compartment) as well as antibody secreting plasma cells that can neutralize and limit free virus. A concerted second wave of assault against the virus will require the activation and recruitment of antigen specific memory CD4+ and CD8+ T cells in mesenteric lymph nodes and distal secondary lymphoid organs. New delivery strategies targeting the “right” DC subsets in combination with delivery of mucosal adjuvants and innate signals for activating DC will be essential for mucosal vaccines in order to circumvent the naturally tolerogenic environment and the induction of Tregs. Mucosal delivery of antigen in combination with inflammatory signals has been shown to empower systemic immunization by directing responses to mucosal sites for imprinting optimum mucosal memory. Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines.
Human CD8+CXCR3+ T cells have the same function as murine CD8+CD122+ Treg
Authors: Shi Zhe , Okuno Yusuke , Rifa'i Muhaimin , Endharti Agustina Tri , Akane Kazuyuki , Isobe Ken‐ichi , Suzuki Haruhiko 
Published: July 2009

AbstractThe importance of CD8+CD122+ Treg in the maintenance of immune homeostasis has been previously demonstrated in mice. Because the expression pattern of CD8 and CD122 in humans is different from that in mice, human CD8+ Treg that correspond to the murine CD8+CD122+ Treg have not been identified. In this study, we performed DNA microarray analyses to compare the gene expression profiles of CD8+CD122+ cells and CD8+CD122− cells in mice and found that CXCR3 was preferentially expressed in CD8+CD122+ cells. When we analyzed the expression of CD122 and CXCR3 in murine CD8+ cells, we observed a definite population of CD122+CXCR3+ cells. CD8+CXCR3+ cells in mice showed similar regulatory activities to CD8+CD122+ cells by in vivo and in vitro assays. While CD8+CD122+CXCR3+ cells are present in mice, CD8+CXCR3+ cells, but not CD8+CD122+ cells, are present in humans. In the in vitro assay, human CD8+CXCR3+ cells showed the regulatory activity of producing IL‐10 and suppressing IFN‐γ production from CD8+CXCR3− cells. These results suggest that human CD8+CXCR3+ T cells are the counterparts of murine CD8+CD122+ Treg.