bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of phosphatidylinositol 3-kinase signaling in hepatic stellate cells blocks the progression of hepatic fibrosis #
Authors: Son Gakuhei , Hines Ian N. , Lindquist Jeff , Schrum Laura W. , Rippe Richard A. 
Published: July 2009

Abstract
The hepatic stellate cell (HSC) is the primary cell type in the liver responsible for excess collagen deposition during fibrosis. Following a fibrogenic stimulus the cell changes from a quiescent vitamin A–storing cell to an activated cell type associated with increased extracellular matrix synthesis and increased cell proliferation. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been shown to regulate several aspects of HSC activation in vitro, including collagen synthesis and cell proliferation. Using a targeted approach to inhibit PI3K signaling specifically in HSCs, we investigated the role of PI3K in HSCs using a rodent model of hepatic fibrosis. An adenovirus expressing a dominant negative form of PI3K under control of the smooth muscle α-actin (αSMA) promoter was generated (Ad-SMAdnPI3K). Transducing HSCs with Ad-SMAdnPI3K resulted in decreased proliferation, migration, collagen expression, and several additional profibrogenic genes, while also promoting cell death. Inhibition of PI3K signaling was also associated with reduced activation of Akt, p70 S6 kinase, and extracellular regulated kinase signaling as well as reduced cyclin D1 expression. Administering Ad-SMAdnPI3K to mice following bile duct ligation resulted in reduced HSC activation and decreased extracellular matrix deposition, including collagen expression. A reduction in profibrogenic mediators, including transforming growth factor beta, tissue inhibitor of metalloproteinase 1, and connective tissue growth factor was also noted. However, liver damage, assessed by alanine aminotransferase levels, was not reduced. Conclusion: Inhibition of PI3K signaling in HSCs during active fibrogenesis inhibits extracellular matrix deposition, including synthesis of type I collagen, and reduces expression of profibrogenic factors. These data suggest that targeting PI3K signaling in HSCs may represent an effective therapeutic target for hepatic fibrosis. (Hepatology 2009.)
Vitamin D mediates its action in human colon carcinoma cells in a calcium‐sensing receptor‐dependent manner: downregulates malignant cell behavior and the expression of thymidylate synthase and survivin and promotes cellular sensitivity to 5‐FU
Authors: Liu Guangming , Hu Xin , Chakrabarty Subhas 
Published: July 2009

AbstractVitamin D (VD) protects against colon carcinogenesis by mechanisms not fully understood. We had earlier reported on the similarity in the biologic action of VD and that of the calcium‐sensing receptor (CaSR) in human colon carcinoma cells. At the molecular level, the CaSR gene contains 2 VD response elements and VD stimulates the expression of CaSR. In this study, we investigated on the relationship between VD action and CaSR function. We determined and compared the action of VD in human colon carcinoma cells (CBS, Moser, Caco‐2 and HCT116) and their CaSR knocked‐down counterparts. VD inhibited cellular proliferation, cellular invasion, and anchorage‐independent growth and stimulated the expression of p21/Waf1 but not in CaSR knocked‐down cells. These results demonstrate, for the first time, that the known tumor‐suppressive function of VD requires functional CaSR and knocking down CaSR expression abrogated this function of VD. We recently reported that activation of CaSR in human colon carcinoma cells downregulated the expression of thymidylate synthase (TS) and survivin and promoted a significant increase in sensitivity to cytotoxic drugs. We now demonstrate, for the first time, that VD suppressed the expression of TS and survivin, TS and survivin gene transcriptional activities and promoted a cytotoxic response to 5‐FU in a CaSR‐dependent manner. Ectopic expression of wild‐type CaSR in colon carcinoma cells also inhibited the expression of TS and survivin and enhanced cellular sensitivity to 5‐FU. VD, however, could no longer enhance cellular sensitivity to 5‐FU in cells overexpressing CaSR.
Tip‐enhanced Raman scattering studies of histidine on novel silver substrates
Authors: Deckert‐Gaudig Tanja , Deckert Volker 
Published: July 2009

AbstractTip‐enhanced Raman scattering (TERS) experiments of histidine immobilized on an atomically flat silver surface are presented. The substrate consists of silver nanoplates with a diameter of a few micrometers and a height about 20 nm. At such heights, the plates are still transparent to visible wavelengths, which is important for optimal illumination and detection. The Raman spectroscopic results strongly support a homogeneous adsorption of chemically different states of histidine on the silver surface. In addition, the influence of the silver surface and the TERS tip on the spectra of histidine is discussed with respect to the multiple coordination centers in the molecule. Copyright © 2009 John Wiley & Sons, Ltd.
Determination of purine alkaloids and catechins in different parts of Camellia assamica var. kucha by HPLC‐DAD/ESI‐MS/MS
Authors: Lu Jia‐Li , Wang Dong‐Mei , Shi Xiang‐Gang , Yang De‐Po , Zheng Xin‐Qiang , Ye Chuang‐Xing 
Published: July 2009

AbstractBACKGROUND: Kucha (Camellia assamica var. kucha) is a novel wild tea resource grown in China and a tea plant containing a sizable amount of theacrine (1,3,7,9‐tetramethyluric acid). High‐performance liquid chromatography (HPLC) analysis of purine alkaloids and catechins in young leaves of Kucha has been reported previously. However, the compositions of purine alkaloids and catechins in other parts of the plant remain unknown, and more information about the chemical constituents of Kucha is also necessary for further research and development of this new tea resource.RESULTS: Using HPLC with diode array detection coupled with electrospray ionisation tandem mass spectrometry (HPLC‐DAD/ESI‐MS/MS), three purine alkaloids, seven catechins and four non‐catechin phenolic compounds were identified or tentatively identified in Kucha. Purine alkaloids and catechins in leaves at different developmental stages, flowers, stems, pericarps and seeds of the plant were also quantified for the first time by the HPLC method, which was fully validated. Recoveries of the quantified compounds ranged from 96.67 to 104.33%.CONCLUSION: The results showed that the total contents of purine alkaloids and catechins were highest in young leaves of Kucha. Theacrine was detected in all parts of the plant and found to be most abundant in pericarps. Copyright © 2009 Society of Chemical Industry
Post‐treatment of Ganoderma lucidum reduced liver fibrosis induced by thioacetamide in mice
Authors: Wu Yueh‐Wern , Fang Hsun‐Lang , Lin Wen‐Chuan 
Published: July 2009

AbstractThe present study was aimed at assessing the effects of Ganoderma lucidum extract (GLE) on an established liver fibrosis model with reference to the previously reported hepatoprotective effect of GLE against CCl4‐induced fibrosis in rats. Repeated administration of thioacetamide (TAA) for 12 weeks to mice induced liver fibrosis. Treatment with GLE after the induction of liver fibrosis decreased the hepatic hydroxyproline content and improved liver histology. RT‐qPCR analysis showed that GLE treatment reduced the mRNA expression of collagen (α1)(I), smooth muscle α‐actin, tissue inhibitor of metalloproteinase 1 and metalloproteinase‐13. In addition, the TAA‐induced decrease in total collagenase activity was reversed by GLE treatment. In conclusion, oral administration of GLE reversed TAA‐induced liver fibrosis, the mechanism of which might be related to the enhancement of collagenase activity. Copyright © 2009 John Wiley & Sons, Ltd.
Experience with an extensible workspace for analysis of low‐level usage data
Authors: Thomas Richard C. , Karahasanović Amela 
Published: July 2009

AbstractAnalysis of low‐level usage data collected in empirical studies of user interaction is well known as a demanding task. Existing techniques for data collection and analysis are either application specific or data‐driven. This paper presents a workspace for data cleaning, transformation and analysis of low‐level usage data that we have developed and reports our experience with it. By its five‐level architecture, the workspace makes a distinction between more general data that typically can be used in initial data analysis and the data answering a specific research question. The workspace was used in four studies and in total 6.5M user actions were collected from 238 participants. The collected data have been proven to be useful for: (i) validating solution times, (ii) validating process conformances, (iii) exploratory studies on program comprehension for understanding use of classes and documents and (iv) testing hypotheses on keystroke latencies. We have found workspace creation to be demanding in time. Particularly demanding were determining the context of actions and dealing with deficiencies. However, once these processes were understood, it was easy to reuse the workspace for different experiments and to extend it to answer new research questions. Based on our experience, we give a set of guidelines that might help in setting up studies, collecting and preparing data. We recommend that designers of data collection instruments add context to each action. Furthermore, we recommend rapid iterations starting early in the process of data preparation and analysis, and covering both general and specific data. Copyright © 2009 John Wiley & Sons, Ltd.
Regulatory roles of transforming growth factor beta family members in folliculogenesis
Authors: Myers Michelle , Pangas Stephanie A. 
Published: July 2009

AbstractBidirectional signaling between the oocyte and surrounding somatic cells is absolutely essential for successful germ cell development in mammals. Oocytes secrete proteins that are necessary for granulosa cells growth and differentiation, whilst granulosa cells regulate oocyte development and integrate ovarian function with the rest of the body by orchestrating gonadal steroidogenesis. The importance of communication between the oocyte and granulosa cells is highlighted by genetic deletion of members of the transforming growth factor beta (TGFβ) family and their downstream signaling components. Such knockout models have uncovered an interesting spectrum of reproductive phenotypes that have greatly advanced our knowledge of ovarian function and dysfunction. The current review focuses on some of the more recent transgenic mouse models that elucidate the intraovarian TGFβ signaling vital for oocyte and granulosa cell development. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:

Developmental Biology > Lineages
A Novel Robot-Assisted Technique for Excision of a Posterior Mediastinal Thyroid Goiter
Authors: Podgaetz Eitan , Gharagozloo Farid , Najam Farzad , Sadeghi Nader , Margolis Marc , Tempesta Barbara J. 
Published: July 2009

Objective Intrathoracic thyroid goiter is an uncommon condition. Most goiters are found in the superior and anterior mediastinum, which can be removed either through a cervical approach or through a combined cervicotomy and sternotomy approach. Extension of the goiter into the posterior mediastinum is even less common. Transcervival approach to thyroid goiters in the posterior mediastinum can be difficult, necessitating a thoracotomy, with its associated morbidity. Methods A 69-year-old patient underwent robotic assisted minimally invasive procedure, with the daVinci surgical robotic system to excise a thyroid goiter that extended into the posterior mediastinum. The blood supply of the mediastinal portion of the goiter originated from the right internal thoracic artery. The thoracic and mediastinal portion of the goiter was approached with robot-assisted minimally invasive surgical techniques. Small incisions were used to gain access to the posterior mediastinum via the right pleural cavity, obviating the need for thoracotomy. Using precise movements of the robotic arm, the mediastinal part of the goiter was dissected off vital structures, from within the posterior mediastinum. Total thyroidectomy was then completed using the cervical approach. Results The patient tolerated the procedure well, with minimal intraoperative blood loss. The patient was discharged home after a short hospital stay. Conclusions Robotic surgical techniques for removal of a substernal goiter and other thyroid masses with mediastinal extension, in combination with cervical incision, are effective. Robotic-assisted techniques can complement video-assisted thoracic surgical techniques and broaden the indications for minimally invasive surgery.
Fast Track Minimally Invasive Transmyocardial Revascularization
Authors: Wehberg Kurt E. , Jackson Debra , Walters Joseph , Redmond Brandon , Todd James C. , Ogburn Nicholas L. , Leonard Steven 
Published: July 2009

Objective We evaluated the initial results of a fast-track discharge protocol for patients undergoing minimally invasive transmyocardial revascularization (MiTMR). Methods Fifteen male patients, aged 64.5 ± 9.2 years, with an ejection fraction of 46.8% ± 9.9%, underwent MiTMR through a mini-left anterior thoracotomy aided by robotic-controlled thoracoscopic assistance. A postoperative management protocol included immediate extubation, early chest tube and pulmonary artery catheter removal, and mobilization within 12 hours. Results There were no operative arrhythmias or in-hospital mortalities. Three of 15 patients developed left lower lobe atelectasis, delaying discharge between 2 and 5 days. Overall hospital length of stay was 1.4 ± 1.2 days, although 12 of 15 patients (80%) were discharged to home in 23 hours. Mild-moderate cardiomyopathy (ejection fraction 30%–50%) was not associated with prolonged length of stay. Mean hospital profit margin was $1882.50. One 30-day readmission occurred on day 23 for rapid atrial fibrillation, and one death occurred on day 11. Conclusions Despite these high-risk patients having end-staged, ischemic coronary artery disease, most MiTMR patients can be discharged to home in less than 24 hours. Perioperative morbidity and mortality rates are relatively low, and hospital profit margins are modest.
Seasonal changes in suppressive capacity of CD4+ CD25+ T cells from patients with hayfever are allergen‐specific and may result in part from expansion of effector T cells among the CD25+ population
Authors: Anderson A. E. , Mackerness K. J. , Aizen M. , Carr V. A. , Nguyen D. , Pre F. Du , Durham S. R. , Robinson D. S. 
Published: July 2009

SummaryBackground
Suppression of allergen‐stimulated peripheral blood CD4+ CD25− effector T cells by CD4+ CD25+ regulatory T cells obtained from subjects with allergic rhinoconjunctivitis is reduced during the pollen season when compared with out of season.Objective
We examined possible explanations for this effect of seasonal pollen exposure on suppression of allergen responses.Methods
CD4+ CD25− and CD4+ CD25+ T cells were isolated from blood obtained from 44 volunteers with allergic rhinoconjunctivitis during and out of the UK grass pollen season. Co‐cultures were performed with grass pollen extract and house dust mite (HDM) to examine allergen specificity. The frequency of IL‐5 and IL‐10 producing cells was determined by ELISPOT and the expression of T cell activation markers and the CD25+ regulatory T cell‐associated transcription factor Foxp3 were examined. Lactic acid stripping of IgE was used to determine IgE dependence of T cell responses.Results
The seasonal reduction in suppression by CD4+ CD25+ T cells was confirmed and was shown to be allergen specific because suppression of HDM‐stimulated cultures was not affected significantly. The CD4+ CD25+ population contained IL‐5 and IL‐10 producing cells but increases in their frequencies with seasonal pollen exposure were not significant. Both activation marker and Foxp3 expression increased during the pollen season. IgE stripping reduced CD4+ and CD4+ CD25− T cell responses to allergen, but had no effect on suppression by CD4+ CD25+ T cells.Conclusion
The seasonal reduction in suppression of grass pollen‐stimulated effector T cells by CD4+ CD25+ T cells is allergen specific and cannot be explained by increased IgE‐facilitated allergen presentation. We suggest that changes in the proportion of effector to regulatory T cells among the CD25+ population isolated may partially explain these findings, and that trafficking to the site of allergic disease may reduce allergen‐specific regulatory T cell numbers in peripheral blood.
The definition and diagnosis of Asthma
Authors: Hargreave F. E. , Nair P. 
Published: July 2009

SummaryThe diagnosis of asthma depends on what we mean by the word. Its definition continues to be controversial because there is no single genetic or environmental cause. Addressed from a descriptive point of view, the disease components include airway inflammation, symptoms, variable airflow limitation and chronic airflow limitation. The essentialist definition conveys the message that asthma is a separate disease entity, fails to identify a primary defining characteristic which separates it from other diseases and is long winded. These disadvantages are overcome by the nominalist definition of asthma in which the word ‘asthma’refers to an abnormality of airway function, specifically to wide variations in airflow limitation over short periods of time. In patients with asthma the other components of airway disease need to be considered. These have separate nominalist definitions and especially include different types of bronchitis for airway inflammation and chronic obstructive pulmonary disease for chronic airflow limitation. What is present will vary between and within patients. The accurate diagnosis of asthma and of other components of disease all require objective measurements. Currently spirometry and airway responsiveness should be available to the general practitioner, who sees milder disease, and additional quantitative sputum cell counts in specialist practice, where moderate to severe disease is more prevalent. Such measurements characterize the patient, identify heterogeneity and allow treatment to be personalized.
Haemopoietic processes in allergic disease: eosinophil/basophil development
Authors: Gauvreau G. M. , Ellis A. K. , Denburg J. A. 
Published: July 2009

SUMMARYHaemopoietic myeloid progenitors contribute to the ongoing recruitment of pro‐inflammatory cells, such as eosinophils and basophils (Eo/B), to target tissue sites in allergic diseases. It is apparent that the development of allergic inflammation is critically dependent on the ability of the bone marrow to support the proliferation, differentiation and mobilization of haemopoietic progenitors. The haemopoietic inductive microenvironment in the bone marrow is crucial for providing signals necessary for maintenance of progenitor populations at varying stages of lineage commitment and permitting these cells to circulate in the bloodstream. Progenitors demonstrate responsiveness to specific cytokines, which varies with stage of differentiation. Pro‐inflammatory signals, Th2 cytokines in particular, generated following allergen challenge, can impact on haemopoietic progenitor differentiation and mobilization, leading to accelerated Eo/B production. Allergen inhalation by allergic asthmatics induces a time‐dependent change in cytokine levels within the bone marrow compartment, influencing differentiation of Eo/B progenitors, as evidenced by the relationship between increased bone marrow IL‐5 levels and Eo/B production. It is proposed that inhaled allergen induces trafficking of IL‐5‐producing T lymphocytes to the bone marrow, further promoting eosinophilopoiesis through IL‐5R signalling. In this manner, Th2 lymphocyte trafficking from the airway may regulate events occurring in the bone marrow. Negative regulators of Eo/B differentiation, including Th1 cytokines, may prove to be important for restoring homeostasis. Eo/B progenitors are also altered in cord blood of infants at risk of atopy and asthma, offering a potential biomarker for, and raising the possibility that Eo/B progenitors are directly involved in the development of allergic disease. For example, changes in the expression of haemopoietic cytokine receptors on cord blood progenitor cells are associated with maternal allergic sensitization, atopic risk and its development, suggesting that haemopoietic processes underlying the allergic phenotype may begin to evolve in the perinatal period.
Protein expression in salivary glands of rats with streptozotocin diabetes
Authors: Mednieks Maija I. , Szczepanski Andrew , Clark Brett , Hand Arthur R. 
Published: July 2009

SummaryDiabetes mellitus (DM) is a widespread disease with high morbidity and health care costs. An experimental animal model was employed, using morphological and biochemical methods, to investigate the effects of DM on the expression and compartmentation of salivary gland proteins. The distribution of proline‐rich proteins (PRP), submandibular mucin (Muc10) and the regulatory (RI and RII) subunits of cyclic AMP‐dependent protein kinase type I and type II was determined in the parotid and submandibular (SMG) glands of rats treated with streptozotocin. Quantitative immunocytochemistry of secretory granules in diabetic glands revealed decreases of 30% for PRP in both the parotid and SMG, and a 40% decrease in Muc10 in the SMG. Immunogold labelling showed that RII decreased in nuclei and the cytoplasm in diabetic acinar cells while labelling of secretory granules was similar in control and diabetic parotid. Electrophoresis and Western blotting of tissue extracts of two secretory proteins showed that the response to DM and insulin treatment was gland specific: PRP showed little change in the SMG, but decreased in the parotid in DM and was partially restored after insulin treatment. Photoaffinity labelling showed only RI present in the SMG and mainly RII in the parotid. The results of this and previous studies demonstrating highly specific changes in salivary protein expression indicate that the oral environment is significantly altered by DM, and that oral tissues and their function can be compromised. These findings may provide a basis for future studies to develop tests using saliva for diabetic status or progression in humans.
Blue fish burgers: nutritional characterisation and sensory optimisation
Authors: Di Monaco Rossella , Cavella Silvana , Masi Paolo , Sevi Agostino , Caroprese Mariangela , Marzano Alessandra , Conte Amalia , Del Nobile Matteo Alessandro 
Published: July 2009

SummaryIn order to reduce waste of marine resources, valorise fishing discards and move towards fish consumption, a new ready‐to‐cook seafood product was developed. In particular, a chemical investigation on chub mackerel and hake was conducted to the aim of mixing the two fish species to produce nutritionally balanced fish burgers. In addition, to evaluate consumer opinion about these new fresh products and best acceptability of different proportions of mackerel and hake, focus group interviews and consumer test were also performed. The results of the chemical analyses achieved on both selected fish species gave rise to minimally processed fish products with a high amount of chub mackerel, therefore providing the desired nutritional properties and low level of hake in order to obtain firmer and wetter burgers. By means of focus group interviews, the novelty and high level of convenience of the developed fresh commodity was highlighted. Consumer test declared that the most successful sample was that with 70% chub mackerel and 30% hake.