bluuebunny/crossref_metadata_2025_split huggingface dataset:
T Cell Factor 1 Regulates Thymocyte Survival via a RORγt-Dependent Pathway
Authors: Wang Ruiqing , Xie Huimin , Huang Zhaofeng , Ma Jian , Fang Xianfeng , Ding Yan , Sun Zuoming 
Published: October 2011

Abstract
Survival of CD4+CD8+ double-positive (DP) thymocytes plays a critical role in shaping the peripheral T cell repertoire. However, the mechanisms responsible for the regulation of DP thymocyte lifespan remain poorly understood. In this work, we demonstrate that T cell factor (TCF)-1 regulates DP thymocyte survival by upregulating RORγt. Microarray analysis revealed that RORγt was significantly downregulated in TCF-1−/− thymocytes that underwent accelerated apoptosis, whereas RORγt was greatly upregulated in thymocytes that had enhanced survival due to transgenic expression of a stabilized β-catenin (β-catTg), a TCF-1 activator. Both TCF-1−/− and RORγt−/− DP thymocytes underwent similar accelerated apoptosis. Forced expression of RORγt successfully rescued TCF-1−/− DP thymocytes from apoptosis, whereas ectopically expressed TCF-1 was not able to rescue the defective T cell development because of the lack of RORγt-supported survival. Furthermore, activation of TCF-1 by stabilized β-catenin was able to enhance DP thymocyte survival only in the presence of RORγt, indicating that RORγt acts downstream of TCF-1 in the regulation of DP thymocyte survival. Moreover, β-catenin/TCF-1 directly interacted with the RORγt promoter region and stimulated its activity. Therefore, our data demonstrated that TCF-1 enhances DP thymocyte survival through transcriptional upregulation of RORγt, which we previously showed is an essential prosurvival molecule for DP thymocytes.
Adenosinergic Regulation of the Expansion and Immunosuppressive Activity of CD11b+Gr1+ Cells
Authors: Ryzhov Sergey , Novitskiy Sergey V. , Goldstein Anna E. , Biktasova Asel , Blackburn Michael R. , Biaggioni Italo , Dikov Mikhail M. , Feoktistov Igor 
Published: October 2011

AbstractExtracellular adenosine and purine nucleotides are elevated in many pathological situations associated with the expansion of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). Therefore, we tested whether adenosinergic pathways play a role in MDSC expansion and functions. We found that A2B adenosine receptors on hematopoietic cells play an important role in accumulation of intratumoral CD11b+Gr1high cells in a mouse Lewis lung carcinoma model in vivo and demonstrated that these receptors promote preferential expansion of the granulocytic CD11b+Gr1high subset of MDSCs in vitro. Flow cytometry analysis of MDSCs generated from mouse hematopoietic progenitor cells revealed that the CD11b+Gr-1high subset had the highest levels of CD73 (ecto-5′-nucleotidase) expression (Δmean fluorescence intensity [MFI] of 118.5 ± 16.8), followed by CD11b+Gr-1int (ΔMFI of 57.9 ± 6.8) and CD11b+Gr-1−/low (ΔMFI of 12.4 ± 1.0) subsets. Even lower levels of CD73 expression were found on Lewis lung carcinoma tumor cells (ΔMFI of 3.2 ± 0.2). The high levels of CD73 expression in granulocytic CD11b+Gr-1high cells correlated with high levels of ecto-5′-nucleotidase enzymatic activity. We further demonstrated that the ability of granulocytic MDSCs to suppress CD3/CD28-induced T cell proliferation was significantly facilitated in the presence of the ecto-5′-nucleotidase substrate 5′-AMP. We propose that generation of adenosine by CD73 expressed at high levels on granulocytic MDSCs may promote their expansion and facilitate their immunosuppressive activity.
Glycogen Synthase Kinase-3β Is a Prosurvival Signal for the Maintenance of Human Mast Cell Homeostasis
Authors: Rådinger Madeleine , Smrž Daniel , Metcalfe Dean D. , Gilfillan Alasdair M. 
Published: October 2011

Abstract
Homeostasis of mature tissue-resident mast cells is dependent on the relative activation of pro- and antiapoptotic regulators. In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) in the survival of neoplastic and nonneoplastic human mast cells. GSK3β was observed to be phosphorylated at the Y216 activating residue under resting conditions in both the neoplastic HMC1.2 cell line and in peripheral blood-derived primary human mast cells (HuMCs), suggesting constitutive activation of GSK3β in these cells. Lentiviral-transduced short hairpin RNA knockdown of GSK3β in both the HMC1.2 cells and HuMCs resulted in a significant reduction in cell survival as determined with the MTT assay. The decrease in stem cell factor (SCF)-mediated survival in the GSK3β knockdown HuMCs was reflected by enhancement of SCF withdrawal-induced apoptosis, as determined by Annexin V staining and caspase cleavage, and this was associated with a pronounced reduction in SCF-mediated phosphorylation of Src homology 2 domain-containing phosphatase 2 and ERK1/2 and reduced expression of the antiapoptotic proteins Bcl-xl and Bcl-2. These data show that GSK3β is an essential antiapoptotic factor in both neopastic and nontransformed primary human mast cells through the regulation of SCF-mediated Src homology 2 domain-containing phosphatase 2 and ERK activation. Our data suggest that targeting of GSK3β with small m.w. inhibitors such as CHIR 99021 may thus provide a mechanism for limiting mast cell survival and subsequently decreasing the intensity of the allergic inflammatory response.
α9β1 Integrin-Mediated Signaling Serves as an Intrinsic Regulator of Pathogenic Th17 Cell Generation
Authors: Kanayama Masashi , Morimoto Junko , Matsui Yutaka , Ikesue Masahiro , Danzaki Keiko , Kurotaki Daisuke , Ito Koyu , Yoshida Toshimichi , Uede Toshimitsu 
Published: October 2011

Abstract
The interaction between matricellular proteins such as tenascin-C (TN-C) and osteopontin (OPN) and integrins has been implicated in the pathology of rheumatoid arthritis in which Th17 cells are recognized as primary pathogenic cells. The differentiation of Th17 cells is tightly regulated by cytokines derived from APCs, receiving various signals including TLR stimuli. In this study, we used a collagen-induced arthritis model and found that increased numbers of α9 integrin-positive conventional dendritic cells and macrophage were detectable in the draining lymph node (dLN) shortly following first immunization, and these cells produced both TN-C and OPN, ligands for α9 integrin. α9 integrin-mediated signaling, induced by TN-C and OPN, promoted the production of Th17-related cytokines by conventional dendritic cells and macrophages in synergy with TLR2 and 4 signaling. This led to the Th17 cell differentiation and arthritis development. Moreover, Th17 cells generated under blocking of α9 integrin-mediated signaling showed low level of CCR6 expression and impaired migration ability toward CCL20. Thus, we have identified α9 integrin-mediated signaling by TN-C and OPN as a novel intrinsic regulator of pathogenic Th17 cell generation that contributes to the development of rheumatoid arthritis.
A p53 Defect Sensitizes Various Stages of B Cell Development to Lymphomagenesis in Mice Carrying an IgH 3′ Regulatory Region-Driven c-myc Transgene
Authors: Fiancette Rémi , Rouaud Pauline , Vincent-Fabert Christelle , Laffleur Brice , Magnone Virginie , Cogné Michel , Denizot Yves 
Published: October 2011

Abstract
Although c-myc is classically described as the driving oncogene in Burkitt’s lymphoma (BL), deregulation and mutations of c-myc have been reported in multiple solid tumors and in other mature B cell malignancies such as mantle cell lymphoma (MCL), myeloma, and plasma cell lymphoma (PCL). After translocation into the IgH locus, c-myc is constitutively expressed under the control of active IgH enhancers. Those located in the IgH 3′ regulatory region (3′RR) are master control elements of class switch recombination and of the transcriptional burst associated with plasma cell differentiation. c-myc-3′RR mice are prone to lymphomas with rather homogeneous, most often BL-like, phenotypes with incomplete penetrance (75% tumor incidence) and long latencies (10–12 mo). To reproduce c-myc–induced mature B cell lymphomagenesis in the context of an additional defect often observed in human lymphomas, we intercrossed c-myc-3′RR with p53+/− mice. Double transgenic c-myc-3′RR/p53+/− mice developed lymphoma with short latency (2–4 mo) and full penetrance (100% tumor incidence). The spectrum of B lymphomas occurring in c-myc-3′RR/p53+/− mice was widened, including nonactivated (CD43−) BL, activated (CD43+) BL, MCL-like lymphoma, and PCL, thus showing that 3′RR-mediated deregulation of c-myc can promote various types of B lymphoproliferation in cells that first acquired a p53 defect. c-myc/p53+/− mice closely reproduce many features of BL, MCL, and PCL and provide a novel and efficient model to dissect the molecular events leading to c-myc–induced lymphomagenesis and an important tool to test potential therapeutic agents on malignant B cells featuring various maturation stages.
Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development
Authors: Patel Kamlesh , Jhamb Sarbjit Singh , Singh Prati Pal 
Published: October 2011

ABSTRACTLatent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.
Agreement of Two Different Laboratory Methods Used to Measure Electrolytes
Authors: Albert Venencia , Subramanian Arulselvi , Rangarajan Kanchana , Pandey Ravindra Mohan 
Published: October 2011

ABSTRACT
Aim: The aim of our study was to do an agreement analysis of two different laboratory methods used to measure electrolytes i.e., between the ISE based Beckman Coulter Synchron CX9 PRO Biochemistry analyzer and RAL′s Ion3 Flame Photometer (Técnica para el Laboratorio, Barcelona, Spain), in serum samples.
Materials and Methods: This cross sectional study was done over a period of three months from September′09 through December′09 on routine biochemistry samples. A total of 6492 samples were received for routine biochemistry analysis from those 630 blood samples were randomly processed for this study. Two ml of sample was taken in a plain gel tube (LABTECH Disposables, Ahmedabad, India), centrifuged and further processed using both systems within one hour of the sampling to obtain the Na and K concentrations in the samples. The bias and variability of differences in measured values were analyzed according to Bland and Altman method.
Results: Flame photometry method has drawbacks such as low throughput, requires manual operation, is a time consuming procedure. Ion selective electrodes technique is a more universal method for the high throughput determination of electrolytes in physiological samples; Beckman Coulter Synchron CX9 PRO is an example of such a system. The mean difference between the two methods (standard minus test) and 95% limits of agreement for sodium in serum was -7.8±17.3 (-42.2 to 26.6) and in urine was -22±41 (-104 to 60). Similarly, the mean difference between the two methods for potassium values in serum was found to be -0.25±0.75 (-1.75 to 1.25) and in urine was -5.3±38.9 (-83.1 to 72.5). With 95% confidence interval, the value of sodium and potassium as determined by both the methods lie between the upper and lower limit showing 95% limits of agreement.
Conclusion: Good degree of agreement was seen on comparing the two methods for measuring the electrolytes; the use of Synchron CX9 in place of Flame photometer for electrolyte analysis in serum and urine is justified or use the two interchangeably.
The cytomorphologic spectrum of small-cell carcinoma and large-cell neuroendocrine carcinoma in body cavity effusions: A study of 68 cases
Authors: Khalbuss Walid E. , Yang Huaitao , Lian Qian , Elhosseiny Abdelmonem , Pantanowitz Liron , Monaco Sara E 
Published: October 2011

Background:
Small-cell carcinoma (SCC) and large-cell neuroendocrine carcinoma (LCNEC) are uncommon in serous body cavity effusions. The purpose of this study is to examine the cytomorphological spectrum of SCC and LCNEC in body cavity serous fluids.

Materials and Methods:
We have 68 cases from 53 patients who had metastatic SCC or LCNEC diagnoses. All cytology slides and the available clinical data, histological follow-up, and ancillary studies were reviewed.

Results:
A total of 68 cases (60 pleural, 5 peritoneal, and 3 pericardial effusions) from 53 patients with an average age of 73 years (age range 43-92 years) were reported as diagnostic or suspicious of SCC (52 cases) or LCNEC (16 cases). The primary site was lung in 56 cases, pancreas in 6 cases, and 2 cases each from cervix, colon, and the head and neck region. Of the 68 cases, 48 cases had no history of malignancy of the same type. Ancillary studies were used in 46 cases (68%) including flow cytometric studies in 5 cases. There were three predominant cytomorphological patterns observed including small-cell clusters with prominent nuclear molding (33 cases, 49%), large-cell clusters mimicking non-small-cell carcinoma (18 cases, 26%), and single-cell pattern mimicking lymphoma (17 cases, 25%). Significant apoptosis was seen in 22 cases (33%) and marked tumor cell cannibalism was seen in 11 cases (16%). Nucleoli were prominent in 16 cases (24%). The most frequent neuroendocrine markers performed were synaptophysin and chromogranin.

Conclusions:
The most common cytomorphologic patterns seen in body cavity effusions of SCC and LCNEC were small-cell clusters with nuclear molding. However, in 51% of the cases either a predominant single-cell pattern mimicking lymphoma or large-cell clusters mimicking non-small carcinoma were noted. In our experience, effusions were the first manifestation of disease in the majority of patients diagnosed with neuroendocrine carcinoma. Therefore, familiarity with the cytomorphological spectrum of neuroendocrine carcinomas in fluid cytology may help in rapidly establishing an accurate diagnosis and in directing appropriate management.
Malignancy rate in nondominant nodules in patients with multinodular goiter: Experience with 1,606 cases evaluated by ultrasound-guided fine needle aspiration cytology
Authors: Paksoy Nadir , Yazal Kadri , Çorak Selin 
Published: October 2011

Background:
Conventional medical sources recommend the use of fine needle aspiration cytology (FNAC) for single thyroid nodules and the dominant nodule in multinodular goiter (MNG). The purpose of the present study was to analyze the utility of FNAC for multiple thyroid nodules in patients with MNG and to determine the rate of malignancy in teh nondominant nodules.

Materials and Methods:
Our private practice performed ultrasound-guided FNAC on 1,606 patients between February 2001 and February 1, 2010. In the MNG cases, samples were taken from the dominant nodule and from trhee suspicious / nonsuspicious nodules larger than 1 cm on ultrasound. Ninety-four cases were diagnosed as ‘suspiciously malignant’(SUS) or ‘malignant’ (POS) based on FNAC.

Results:
The rate of an SUS / POS diagnosis was 5.7% in the dominant nodules; 2.3% of the nondominant nodules had a SUS / POS diagnosis in FNAC (p = 0.0003). Follow-up revealed malignancy in 15 (35.7%) nondominant nodules and in 27 (64.2%) dominant nodules, with 42 MNG cases undergoing surgery. X test showed a ‘p-level of 0.0003’ between the percentages of SUS / POS diagnosis in dominanat and nondominanat nodules. It was less than the significance level of 0.05. Therefore, the result was regarded to be statistically significant.

Conclusions:
Nondominant nodules could harbor malignancy. The risk of malignancy in nondominant nodules in MNG should not be underestimated. We have shown that the dominant nodule in patients with MNG was in fact about 2.5 times more likely to be malignant than a nondominant nodule. The use of FNAC for nondominant nodules could enhance the likelihood of detecting malignancy in an MNG.
Randomized Trial of a Computer-Tailored Intervention for Patients with Depression
Authors: Levesque Deborah A. , Van Marter Deborah F. , Schneider Robert J. , Bauer Mark R. , Goldberg David N. , Prochaska James O. , Prochaska Janice M. 
Published: October 2011

Purpose. Examine the efficacy of a computer-tailored intervention (CTI) based on the transtheoretical model (TTM) for reducing depression, an increasingly important component of health promotion programs. Design. Pretest-posttest randomized trial. Setting. Participants were recruited and treated at home after being identified in two primary care clinics in Eastern Massachusetts and Chicago, Illinois. Subjects. A total of 350 adults experiencing at least mild symptoms of depression but not involved in or planning to seek treatment for depression. Intervention. A print manual and three CTI reports tailored to stage of change for using effective methods to prevent or reduce depression, other TTM variables, level of depression, and behavior. Measures. Pre-post changes and reliable and clinically significant change on the Beck Depression scale II and pre-post changes on the 20-item Medical Outcomes Study Short Form survey–based measure of physical functioning at 9 months' follow-up. Analysis. t-tests and χ2 tests. Complete-case analysis and two intention-to-treat analyses—assumption of no change and multiple imputation (MI)—are reported. Exploratory analyses examined whether the effects of the intervention on depression were moderated by five subject characteristics: baseline level of depression, baseline level of physical functioning, baseline stage of change for preventing or managing depression, age, and education. Results. Complete-case and intention-to-treat analyses showed that the intervention group experienced significantly greater improvements in depression (d = .220–.355); results for physical functioning were weaker (d = .150–.309) and did not reach statistical significance in the MI analysis. The effects of the intervention on reliable and clinically significant change in depression were largest among participants who were experiencing moderate depression (d = .363–.519) or severe depression (d = .603–.718) or who were in the precontemplation or contemplation stage (d = .573–.856) at baseline.
The ACTIVATE Study: Results from a Group-Randomized Controlled Trial Comparing a Traditional Worksite Health Promotion Program with an Activated Consumer Program
Authors: Terry Paul E. , Fowles Jinnet Briggs , Xi Min , Harvey Lisa 
Published: October 2011

Purpose. This study compares a traditional worksite-based health promotion program with an activated consumer program and a control program Design. Group randomized controlled trial with 18-month intervention. Setting. Two large Midwestern companies. Subjects. Three hundred and twenty employees (51% response). Intervention. The traditional health promotion intervention offered population-level campaigns on physical activity, nutrition, and stress management. The activated consumer intervention included population-level campaigns for evaluating health information, choosing a health benefits plan, and understanding the risks of not taking medications as prescribed. The personal development intervention (control group) offered information on hobbies. The interventions also offered individual-level coaching for high risk individuals in both active intervention groups. Measures. Health risk status, general health status, consumer activation, productivity, and the ability to evaluate health information. Analysis. Multivariate analyses controlled for baseline differences among the study groups. Results. At the population level, compared with baseline performance, the traditional health promotion intervention improved health risk status, consumer activation, and the ability to recognize reliable health websites. Compared with baseline performance, the activated consumer intervention improved consumer activation, productivity, and the ability to recognize reliable health websites. At the population level, however, only the activated consumer intervention improved any outcome more than the control group did; that outcome was consumer activation. At the individual level for high risk individuals, both traditional health coaching and activated consumer coaching positively affected health risk status and consumer activation. In addition, both coaching interventions improved participant ability to recognize a reliable health website. Consumer activation coaching also significantly improved self-reported productivity. Conclusion. An effective intervention can change employee health risk status and activation both at the population level and at the individual high risk level. However, program engagement at the population level was low, indicating that additional promotional strategies, such as greater use of incentives, need to be examined. Less intensive coaching can be as effective as more intensive, albeit both interventions produced modest behavior change and retention in the consumer activation arm was most difficult. Further research is needed concerning recruitment and retention methods that will enable populations to realize the full potential of activated consumerism.