bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT2 Contributes to Promotion of Colorectal and Skin Carcinogenesis
Authors: Gamero Ana M. , Young Matthew R. , Mentor-Marcel Roycelynn , Bobe Gerd , Scarzello Anthony J. , Wise Jennifer , Colburn Nancy H. 
Published: March 2010

Abstract
Signal transducer and activator of transcription 2 (STAT2) is an essential transcription factor in the type I IFN (IFN-α/β) signal transduction pathway and known for its role in mediating antiviral immunity and cell growth inhibition. Unlike other members of the STAT family, IFNs are the only cytokines known to date that can activate STAT2. Given the inflammatory and antiproliferative dual nature of IFNs, we hypothesized that STAT2 prevents inflammation-induced colorectal and skin carcinogenesis by altering the inflammatory immune response. Contrary to our hypothesis, deletion of STAT2 inhibited azoxymethane/dextran sodium sulfate–induced colorectal carcinogenesis as measured by prolonged survival, lower adenoma incidence, smaller polyps, and less chronic inflammation. STAT2 deficiency also inhibited 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate–induced skin carcinogenesis as indicated by reduced papilloma multiplicity. A potential mechanism by which STAT2 promotes carcinogenesis is through activation of proinflammatory mediators. Deletion of STAT2 decreased azoxymethane/dextran sodium sulfate–induced expression and release of proinflammatory mediators, such as interleukin-6 and CCL2, and decreased interleukin-6 release from skin carcinoma cells, which then decreased STAT3 activation. Our findings identify STAT2 as a novel contributor to colorectal and skin carcinogenesis that may act to increase the gene expression and secretion of proinflammatory mediators, which in turn activate the oncogenic STAT3 signaling pathway. Cancer Prev Res; 3(4); 495–504. ©2010 AACR.
NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects
Authors: Olson Janelle A. , Leveson-Gower Dennis B. , Gill Saar , Baker Jeanette , Beilhack Andreas , Negrin Robert S. 
Published: March 2010

AbstractNatural killer (NK) cells suppress graft-versus-host disease (GVHD) without causing GVHD themselves. Our previous studies demonstrated that allogeneic T cells and NK cells traffic similarly after allogeneic bone marrow transplantation (BMT). We therefore investigated the impact of donor NK cells on donor alloreactive T cells in GVHD induction. Animals receiving donor NK and T cells showed improved survival and decreased GVHD score compared with controls receiving donor T cells alone. Donor T cells exhibited less proliferation, lower CD25 expression, and decreased interferon-γ (IFN-γ) production in the presence of NK cells. In vivo, we observed perforin- and Fas ligand (FasL)–mediated reduction of donor T cell proliferation and increased T cell apoptosis in the presence of NK cells. Further, activated NK cells mediated direct lysis of reisolated GVHD-inducing T cells in vitro. The graft-versus-tumor (GVT) effect was retained in the presence of donor NK cells. We demonstrate a novel mechanism of NK cell–mediated GVHD reduction whereby donor NK cells inhibit and lyse autologous donor T cells activated during the initiation of GVHD.
Investigating determinants of out-of-pocket spending and strategies for coping with payments for healthcare in southeast Nigeria
Authors: Onwujekwe Obinna E , Uzochukwu Benjamin SC , Obikeze Eric N , Okoronkwo Ijeoma , Ochonma Ogbonnia G , Onoka Chima A , Madubuko Grace , Okoli Chijioke 
Published: March 2010

Abstract

Background
Out-of-pocket spending (OOPS) is the major payment strategy for healthcare in Nigeria. Hence, the paper assessed the determinants socio-economic status (SES) of OOPS and strategies for coping with payments for healthcare in urban, semi-urban and rural areas of southeast Nigeria. This paper provides information that would be required to improve financial accessibility and equity in financing within the public health care system.

Methods
The study areas were three rural and three urban areas from Ebonyi and Enugu states in South-east Nigeria. Cross-sectional survey using interviewer-administered questionnaires to randomly selected householders was the study tool. A socio-economic status (SES) index that was developed using principal components analysis was used to examine levels of inequity in OOPS and regression analysis was used to examine the determinants of use of OOPS.

Results
All the SES groups equally sought healthcare when they needed to. However, the poorest households were most likely to use low level and informal providers such as traditional healers, whilst the least poor households were more likely to use the services of higher level and formal providers such as health centres and hospitals. The better-off SES more than worse-off SES groups used OOPS to pay for healthcare. The use of own money was the commonest payment-coping mechanism in the three communities. The sales of movable household assets or land were not commonly used as payment-coping mechanisms. Decreasing SES was associated with increased sale of household assets to cope with payment for healthcare in one of the communities. Fee exemptions and subsidies were almost non-existent as coping mechanisms in this study

Conclusions
There is the need to reduce OOPS and channel and improve equity in healthcare financing by designing and implementing payment strategies that will assure financial risk protection of the poor such pre-payment mechanisms with government paying for the poor.
Epithelial Protein Lost in Neoplasm α (Eplin-α) is transcriptionally regulated by G-actin and MAL/MRTF coactivators
Authors: Leitner Laura , Shaposhnikov Dmitry , Descot Arnaud , Hoffmann Reinhard , Posern Guido 
Published: March 2010

Abstract
Epithelial Protein Lost in Neoplasm α is a novel cytoskeleton-associated tumor suppressor whose expression inversely correlates with cell growth, motility, invasion and cancer mortality. Here we show that Eplin-α transcription is regulated by actin-MAL-SRF signalling. Upon signal induction, the coactivator MAL/MRTF is released from a repressive complex with monomeric actin, binds the transcription factor SRF and activates target gene expression. In a transcriptome analysis with a combination of actin binding drugs which specifically and differentially interfere with the actin-MAL complex (Descot et al., 2009), we identified Eplin to be primarily controlled by monomeric actin. Further analysis revealed that induction of the Eplin-α mRNA and its promoter was sensitive to drugs and mutant actins which stabilise the repressive actin-MAL complex. In contrast, the Eplin-β isoform remained unaffected. Knockdown of MRTFs or dominant negative MAL which inhibits SRF-mediated transcription impaired Eplin-α expression. Conversely, constitutively active mutant actins and MAL induced Eplin-α. MAL and SRF were bound to a consensus SRF binding site of the Eplin-α promoter; the recruitment of MAL to this region was enhanced severalfold upon induction. The tumor suppressor Eplin-α is thus a novel cytoskeletal target gene transcriptionally regulated by the actin-MAL-SRF pathway, which supports a role in cancer biology.
RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones
Authors: Della Peruta Marco , Giagulli Cinzia , Laudanna Carlo , Scarpa Aldo , Sorio Claudio 
Published: March 2010

Abstract

Background
Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mice: S2-m with a low metastatic potential and highly metastatic S2-CP9 using RHOA and PRKCZ cell-permeable inhibitory peptides.

Methods
Adhesion assays, cell permeable peptides, RHOA activity assay, western blotting

Results
When used in combination cell-permeable inhibitory peptides partially inhibited cell adhesion by about 50% in clone S2-CP9. In clone S2-m, the effect was limited to 15% inhibition. In a wound healing assay, S2-CP9 was sensitive only to treatment with the combination of both RHOA and PRKCZ inhibitory peptides. Conversely, S2-m was unable to migrate toward both ends of the wound in basal conditions. Migration of cells through a membrane with 8 μm pores was completely abolished in both clones by individual treatment with RHOA and PRKCZ inhibitory peptides.

Conclusion
Herein, we demonstrate a critical role for RHOA and PRKCZ in the regulation of different aspects of cell motility of pancreatic adenocarcinoma and demonstrate the need to inhibit both pathways to obtain a functionally relevant effect in most assays. These results indicate that RHOA and PRKCZ, and their downstream effectors, can represent important pharmacological targets that could potentially control the highly metastatic attitude of PDAC.
The effect of ageing on human lymphocyte subsets: comparison of males and females
Authors: Yan Jun , Greer Judith M , Hull Renee , O'Sullivan John D , Henderson Robert D , Read Stephen J , McCombe Pamela A 
Published: March 2010

AbstractBackgroundThere is reported to be a decline in immune function and an alteration in the frequency of circulating lymphocytes with advancing age. There are also differences in ageing and lifespan between males and females. We performed this study to see if there were differences between males and females in the frequency of the different lymphocyte subsets with age.ResultsUsing flow cytometry we have examined different populations of peripheral blood leukocytes purified from healthy subjects with age ranging from the third to the tenth decade. We used linear regression analysis to determine if there is a linear relationship between age and cell frequencies. For the whole group, we find that with age there is a significant decline in the percentage of naïve T cells and CD8+T cells, and an increase in the percentage of effector memory cells, CD4+foxp3+T cells and NK cells. For all cells where there was an effect of ageing, the slope of the curve was greater for men than for women and this was statistically significant for CD8+αβ+T cells and CD3+CD45RA-CCR7-effector memory cells. There was also a difference for naïve cells but this was not significant.ConclusionThe cause of the change in percentage of lymphocyte subsets with age, and the different effects on males and females is not fully understood but warrants further study.
Prevalence of a virus similar to human hepatitis B virus in swine
Authors: Li Wengui , She Ruiping , Liu Liqiang , You Hua , Yin Jun 
Published: March 2010

Abstract

Background
The objective of this study is to established evidence of the existence of a novel member of the hepadnavirus family endemic in swine. Temporarily this virus was designated as swine hepatitis B virus (SHBV). This SHBV can be detected by using human hepatitis B virus diagnostic kits including ELISA, immunohistochemical staining, and transmission electron microscopy (TEM). Also seroprevalence of pig farms in Beijing, China, and pathological features of SHBV infection was determined.

Results
Screened result shows that overall prevalence of HBsAg was 24.8%, closed to that of anti-HBsAg, whereas HBeAg and anti-HBe were barely detectable. The distribution of HBsAg and HBcAg was examined by immunohistochemistry of liver samples. Typical hepatitis pathological change, such as spotty parenchymal cell degeneration, necrosis of hepatocytes and proliferation of fibrous connective tissue were observed during histopathological analysis. Analysis of HBsAg-positive serum with TEM revealed two morphologic forms, 20 nm and 40 nm sized particles, similar to small spherical and Danes particles of HBV. Observation of the ultrastructure of the liver also found HBV-like particles in the nucleus of hepatocytes.

Conclusion
Our research result implies that SHBV could be a causative agent of swine. The discovery of SHBV will unveil novel evolutionary aspects of hepatitis and provides new information for further hepadnavirus research.
The eSS rat, a nonobese model of disordered glucose and lipid metabolism and fatty liver
Authors: Daniele Stella M , Montenegro Silvana M , Tarres María C , Picena Juan C , Martinez Stella M 
Published: March 2010

Abstract

Background
eSS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia. Diabetic symptoms worsen during the second year of life as insulin release decreases. In 12-month-old males a diffuse hepatic steatosis was detected. We report the disturbances of lipid metabolism of the model with regard to the diabetic syndrome.

Methods
The study was conducted in eight 12-month-old eSS male rats and seven age/weight matched eumetabolic Wistar rats fed with a complete commercial diet al libitum. Fasting plasmatic glucose, insulin, triglycerides, total cholesterol, low-density and high-density lipoprotein, and nonesterified fatty acids levels were measured. Very low density and intermediate-density lipoproteins were analyzed and hepatic lipase activity was determined.

Results
eSS rats developed hyperglycemia and hyperinsulinemia, indicating insulin resistance. Compared with controls, diabetic rats exhibited high plasmatic levels of NEFA, triglycerides (TG), total cholesterol (Chol) and LDL-Chol while high-density lipoprotein (HDL) cholesterol values were reduced. eSS rats also displayed TG-rich VLDL and IDL particles without changes in hepatic lipase activity.

Conclusion
The nonobese eSS rats develop a syndrome characterized by glucose and lipid disorders and hepatic steatosis that may provide new opportunities for studying the pathogenesis of human type 2 diabetes.
Impact of Tobacco Smoking Cessation on Stable Clozapine or Olanzapine Treatment
Authors: Lowe Erin J , Ackman Margaret L 
Published: March 2010

Objective To examine the pharmacokinetic implications and potential clinical effects of tobacco smoking cessation in patients on stable clozapine or olanzapine treatment. Data sources A literature search of MEDLINE (1950–November 2009) and EMBASE (1980–November 2009) was conducted using the search terms smoking, tobacco, cigarette, cannabis, smoking cessation, cytochrome P450, antipsychotic, clozapine, and olanzapine. In addition, reference lists from publications identified were searched manually. Study selection and data extraction English-language articles and human studies were identified, yielding 111 returns. Articles that reported clinical outcomes following smoking cessation were selected. Pharmacokinetic data for these drugs were reviewed and articles that provided relevant background information were also included. Data synthesis Pharmacokinetic studies have demonstrated more rapid clearance of olanzapine and lower clozapine and norclozapine (desmethylclozapine) concentrations in smokers compared to nonsmokers. These studies also found that smokers require higher doses of these agents than nonsmokers. There are case reports of adverse clinical outcomes following smoking cessation in patients being treated with olanzapine and clozapine. Reports that included serum concentrations consistently found elevations following smoking cessation, and dosage reductions of 30–40% were required to achieve pre-cessation concentrations. Worsening psychiatric symptoms, somnolence, hypersalivation, extreme fatigue, extrapyramidal effects, and seizures have all been reported following smoking cessation in this patient group. Conclusions Pharmacists need to be aware of potential risks associated with smoking cessation in patients stabilized on clozapine or olanzapine. Toxicity as a result of recent smoking reduction or cessation may be a reason for hospital admission. For hospitalized patients, pharmacists should obtain information concerning smoking status, including cessation attempts. Nonspecific signs and symptoms of elevated clozapine or olanzapine concentrations should be considered in relation to clinical status while the patient is hospitalized. Measurement of baseline serum clozapine concentrations and/or empiric dosage adjustment in patients expected to have a prolonged hospital stay with forced smoking cessation may be appropriate.
Recombinant Factor VIIa to Manage Major Bleeding from Newer Parenteral Anticoagulants
Authors: Vavra Kellie A , Lutz Mark F , Smythe Maureen A 
Published: March 2010

Objective To evaluate the use of recombinant factor VIIa (rFVIIa) to reverse major bleeding from newer parenteral anticoagulant therapy. Data sources MEDLINE/PubMed was searched from January 2000 through December 2009 using the terms recombinant factor VIIa, rFVIIa, NovoSeven, enoxaparin, argatroban, fondaparinux, lepirudin, bivalirudin, idraparinux, nadroparin, hirudin, and desirudin. References of identified articles were reviewed. Data synthesis Data evaluating the role of rFVIIa to reverse major bleeding from newer parenteral anticoagulant therapy is limited to case reports and small laboratory investigations. Laboratory investigations suggest that rFVIIa may be effective in reversing the hemostatic effects of newer parenteral anticoagulants. In most case reports analyzed, standard interventions for bleeding (eg, fresh frozen plasma, packed red blood cells) were attempted prior to using rFVIIa. Sixteen published cases describe the use of rFVIIa to reverse major bleeding from low-molecular-weight heparins, synthetic pentasaccharides, and direct thrombin inhibitors. Initial doses ranged from 20 to 120 μg/kg. rFVIIa was considered effective or partially effective based upon clinical response in 13 cases. Use was not effective in 3 cases because of a thrombotic event, no change in hemostasis, and death from bleeding complications. As thrombosis is the major safety concern, an individualized risk-benefit assessment is required prior to the use of rFVIIa therapy to restore hemostasis. Conclusions rFVIIa may be considered to manage major refractory bleeding from newer parenteral anticoagulant agents when the benefit is thought to outweigh the thrombotic risk.
Immediate Hypersensitivity to Moxifloxacin with Tolerance to Ciprofloxacin: Report of Three Cases and Review of the Literature
Authors: Chang Brenda , Knowles Sandra R , Weber Elizabeth 
Published: March 2010

Objective To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. Case summaries A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. Discussion Moxiffoxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. Conclusions Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.
Measurement of excitation functions for production of cerium radioisotopes by deuteron induced reactions on natural cerium for nanobioscience applications
Authors: Simonelli Federica , Abbas Kamel , Chau Huu-tai P. , Holzwarth Uwe , Cydzik I. 
Published: March 2010

Abstract
Cerium based nanoparticles would play an important role in the field of nanotechnology ranging from fuel additives to sun creams, and to various medical applications. Radiolabelled cerium can be accurately and precisely traced during each step of their applications, thanks to the sensitivity of nuclear measurement techniques. This work is focused on the study of the production of cerium radioisotopes and more precisely, as few data are available, on the determination of the excitation functions for production of cerium radioisotopes by deuteron induced nuclear reactions on natural cerium. We measured the excitation functions for the nuclear reactions natCe(d, x)139g,141,143Ce and also for natCe(d, x)142gPr in the energy range of 5 to 18.5 MeV. Theoretical simulations of these excitation functions were performed using the TALYS calculation code. We have shown that with deuteron beam irradiation, several radioisotopes of cerium can be activated and the cross section data of the relevant nuclear reactions are produced for the first time. Thick target yields of 0.1, 1.1 and 3.2 MBq/μA h were reached for 139gCe, 141Ce and 143Ce, respectively, which are sufficient for various biological studies such as cellular uptake of cerium based nanoparticles.
Distribution and Potential Spread of Japanese Knotweed (Polygonum cuspidatum) in Canada Relative to Climatic Thresholds
Authors: Bourchier Robert S. , Van Hezewijk Brian H. 
Published: March 2010

AbstractJapanese knotweed (JK) is one of the most aggressive invasive plants known in the U.K., where its biology has been well-studied. It was introduced into Canada around 1900, but only recently has it become a serious concern in the province of British Columbia (BC). Climatic conditions, including annual degree days and mean-annual minimum temperatures at knotweed sites in British Columbia were modeled in BioSIM, using weather normals and long-term daily weather data, and compared to published thresholds (degree day = 2,505 DD, minimum temperature = −30.2 C, base temperature 0 C). The degree-day threshold was more limiting to JK in British Columbia than mean-minimum temperature (12.3% of province habitat was suitable for JK based on degree days compared with 26% for mean-minimum temperature). A new annual-precipitation threshold of 735 mm/year based on 95% of known knotweed sites in BC was identified. The best-fit logistic regression model included degree days and annual precipitation and predicted knotweed presence/absence with over 97% efficiency. Existing knotweed sites occupy just over half of the suitable habitat in BC, indicating there are still significant areas to be invaded. The limiting threshold for knotweed was reversed in Southern Ontario with between 35 to 53% of the habitat suitable based on minimum temperatures, whereas degree-day accumulations and annual precipitation were not limiting. Warmer temperatures from 2000 to 2008 resulted in an increase to 53% of the habitat in Southern Ontario being suitable for knotweed, compared to 35% when 1971 to 2000 weather normals were used. Different climatic thresholds among provinces might result in selection for different invasive knotweed genotypes. This could influence the success of biological control agents because of differential host suitability of knotweed genotypes. Habitat suitability maps generated will enable better targeting of knotweed surveys based on the risk of knotweed establishment.