bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia
Authors: Scheinberg Phillip , Fischer Steven H. , Li Li , Nunez Olga , Wu Colin O. , Sloand Elaine M. , Cohen Jeffrey I. , Young Neal S. , John Barrett A. 
Published: December 2006

Abstract
The natural history of EBV and CMV reactivation and the potential for serious complications following antibody-based immunosuppressive treatment for bone marrow failure syndromes in the absence of transplantation is not known. We monitored blood for EBV and CMV reactivation by polymerase chain reaction (PCR) weekly in 78 consecutive patients (total of 99 immunosuppressive courses) with aplastic anemia. Four regimens were studied: (1) HC, horse ATG/cyclosporine; (2) HCS, horse ATG/CsA/sirolimus; (3) RC, rabbit ATG/CsA; and (4) CP, alemtuzumab. There were no cases of EBV or CMV disease, but EBV reactivation occurred in 82 (87%) of 94 and CMV reactivation in 19 (33%) of 57 seropositive patients after starting immunosuppression. The median peak EBV copies were higher in the RC group when compared with HC, HCS, and alemtuzumab (P < .001). The median duration of PCR positivity for EBV was higher in the RC group compared with HC, HCS, and alemtuzumab (P = .001). Subclinical reactivation of both EBV and CMV is common and nearly always self-limited in patients with bone marrow failure receiving immunosuppression; different regimens are associated with different intensity of immunosuppression as measured by viral load and lymphocyte count; and viral reactivation patterns differ according to immunosuppressive regimens.
Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia
Authors: Román-Gómez José , Cordeu Lucia , Agirre Xabier , Jiménez-Velasco Antonio , San José-Eneriz Edurne , Garate Leire , Calasanz María José , Heiniger Anabel , Torres Antonio , Prosper Felipe 
Published: December 2006

AbstractActivation of the Wnt/β-catenin signaling pathway is a hallmark of a number of solid tumors. We analyzed the regulation of the Wnt/β-catenin pathway in acute lymphoblastic leukemia (ALL) and its role in the pathogenesis of the disease. We found that expression of the Wnt inhibitors sFRP1, sFRP2, sFRP4, sFRP5, WIF1, Dkk3, and Hdpr1 was down-regulated due to abnormal promoter methylation in ALL cell lines and samples from patients with ALL. Methylation of Wnt inhibitors was associated with activation of the Wnt-signaling pathway as demonstrated by the up-regulation of the Wnt target genes WNT16, FZ3, TCF1, LEF1, and cyclin D1 in cell lines and samples and the nuclear localization of β-catenin in cell lines. Treatment of ALL cells with the Wnt inhibitor quercetin or with the demethylating agent 5-aza-2′-deoxycytidine induced an inactivation of the Wnt pathway and induced apoptosis of ALL cells. Finally, in a group of 261 patients with newly diagnosed ALL, abnormal methylation of Wnt inhibitors was associated with decreased 10-year disease-free survival (25% versus 66% respectively, P < .001) and overall survival (28% versus 61% respectively, P = .001). Our results indicate a role of abnormal Wnt signaling in ALL and establish a group of patients with a significantly worse prognosis (methylated group).
Cohort effects in dynamic models and their impact on vaccination programmes: an example from Hepatitis A
Authors: Srinivasa Rao Arni SR , Chen Maggie H , Pham Ba' Z , Tricco Andrea C , Gilca Vladimir , Duval Bernard , Krahn Murray D , Bauch Chris T 
Published: December 2006

AbstractBackgroundInfection rates for many infectious diseases have declined over the past century. This has created a cohort effect, whereby older individuals experienced a higher infection rate in their past than younger individuals do now. As a result, age-stratified seroprevalence profiles often differ from what would be expected from constant infection rates.MethodsHere, we account for the cohort effect by fitting an age-structured compartmental model with declining transmission rates to Hepatitis A seroprevalence data for Canadian-born individuals. We compare the predicted impact of universal vaccination with and without including the cohort effect in the dynamic model.ResultsWe find that Hepatitis A transmissibility has declined by a factor of 2.8 since the early twentieth century. When the cohort effect is not included in the model, incidence and mortality both with and without vaccination are significantly over-predicted. Incidence (respectively mortality) over a 20 year period of universal vaccination is 34% (respectively 90%) higher than if the cohort effect is included. The percentage reduction in incidence and mortality due to vaccination are also over-predicted when the cohort effect is not included. Similar effects are likely for many other infectious diseases where infection rates have declined significantly over past decades and where immunity is lifelong.ConclusionFailure to account for cohort effects has implications for interpreting seroprevalence data and predicting the impact of vaccination programmes with dynamic models. Cohort effects should be included in dynamic modelling studies whenever applicable.
Heterogeneity of mammary lesions represent molecular differences
Authors: Namba Ruria , Maglione Jeannie E , Davis Ryan R , Baron Colin A , Liu Stephenie , Carmack Condie E , Young Lawrence JT , Borowsky Alexander D , Cardiff Robert D , Gregg Jeffrey P 
Published: December 2006

AbstractBackgroundHuman breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies.MethodsWe utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution.ResultsWe demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes that occur in the transition to invasive carcinoma are subtle, with few consistent changes and no association with phenotype.ConclusionWe propose that the early lesions carry the important genetic changes that reflect the major phenotypic information, while additional genetic changes that accumulate in the invasive carcinoma are less associated with the overall phenotype.
Study protocol of a cluster randomised controlled trial investigating the effectiveness of a tailored energy balance programme for recent retirees
Authors: Werkman Andrea , Schuit Albertine J , Kwak Lydia , Kremers Stef PJ , Visscher Tommy LS , Kok Frans J , Schouten Evert G 
Published: December 2006

Abstract

Background
People in transitional life stages, such as occupational retirement, are likely to gain weight and accumulate abdominal fat mass caused by changes in physical activity and diet. Hence, retirees are an important target group for weight gain prevention programmes, as described in the present paper.

Methods/Design
A systematic and stepwise approach (Intervention Mapping) is used to develop a low-intensity energy balance intervention programme for recent retirees. This one-year, low-intensity multifaceted programme aims to prevent accumulation of abdominal fat mass and general weight gain by increasing awareness of energy balance and influencing related behaviours of participants' preference. These behaviours are physical activity, fibre intake, portion size and fat consumption. The effectiveness of the intervention programme is tested in a cluster randomised controlled trial. Measurements of anthropometry, physical activity, energy intake, and related psychosocial determinants are performed at baseline and repeated at 6 months for intermediate effect, at 12 months to evaluate short-term intervention effects and at 24 months to test the sustainability of the effects.

Discussion
This intervention programme is unique in its focus on retirees and energy balance. It aims at increasing awareness and takes into account personal preferences of the users by offering several options for behaviour change. Moreover, the intervention programme is evaluated at short-term and long-term and includes consecutive outcome measures (determinants, behaviour and body composition).
In vitro cell cultures obtained from different explants of Corylus avellanaproduce Taxol and taxanes
Authors: Bestoso Federica , Ottaggio Laura , Armirotti Andrea , Balbi Alessandro , Damonte Gianluca , Degan Paolo , Mazzei Mauro , Cavalli Francesca , Ledda Bernardetta , Miele Mariangela 
Published: December 2006

Abstract

Background
Taxol is an effective antineoplastic agent, originally extracted from the bark of Taxus brevifolia with a low yield. Many attempts have been made to produce Taxol by chemical synthesis, semi-synthesis and plant tissue cultures. However, to date, the availability of this compound is not sufficient to satisfy the commercial requirements. The aim of the present work was to produce suspension cell cultures from plants not belonging to Taxus genus and to verify whether they produced Taxol and taxanes. For this purpose different explants of hazel (Corylus avellana species) were used to optimize the protocol for inducing in vitro callus, an undifferentiated tissue from which suspension cell cultures were established.

Results
Calli were successfully induced from stems, leaves and seeds grown in various hormone concentrations and combinations. The most suitable callus to establish suspension cell cultures was obtained from seeds. Media recovered from suspension cell cultures contained taxanes, and showed antiproliferative activity on human tumour cells. Taxol, 10-deacetyltaxol and 10-deacetylbaccatin III were the main taxanes identified. The level of Taxol recovered from the media of hazel cultures was similar to that found in yew cultures. Moreover, the production of taxanes in hazel cell cultures increased when elicitors were used.

Conclusion
Here we show that hazel cell cultures produce Taxol and taxanes under controlled conditions. This result suggests that hazel possesses the enzymes for Taxol production, which until now was considered to be a pathway particular to Taxus genus. The main benefit of producing taxanes through hazel cell cultures is that hazel is widely available, grows at a much faster rate in vivo, and is easier to cultivate in vitro than yew. In addition, the production of callus directly from hazel seeds shortens the culture time and minimizes the probability of contamination. Therefore, hazel could become a commercial source of Taxol and taxanes, both to be used as new therapeutic agents or as new precursors for Taxol semi-synthesis.
P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity
Authors: Zhang Lili , Nie Linghu , Maki Carl G 
Published: December 2006

Abstract

Background
p53 is a tumor suppressor and potent inhibitor of cell growth. P73 is highly similar to p53 at both the amino acid sequence and structural levels. Given their similarities, it is important to determine whether p53 and p73 function in similar or distinct pathways. There is abundant evidence for negative cross-talk between glucocorticoid receptor (GR) and p53. Neither physical nor functional interactions between GR and p73 have been reported. In this study, we examined the ability of p53 and p73 to interact with and inhibit GR transcriptional activity.

Results
We show that both p53 and p73 can bind GR, and that p53 and p73-mediated transcriptional activity is inhibited by GR co-expression. Wild-type p53 efficiently inhibited GR transcriptional activity in cells expressing both proteins. Surprisingly, however, p73 was either unable to efficiently inhibit GR, or increased GR activity slightly. To examine the basis for this difference, a series of p53:p73 chimeric proteins were generated in which corresponding regions of either protein have been swapped. Replacing N- and C-terminal sequences in p53 with the corresponding sequences from p73 prevented it from inhibiting GR. In contrast, replacing p73 N- and C-terminal sequences with the corresponding sequences from p53 allowed it to efficiently inhibit GR. Differences in GR inhibition were not related to differences in transcriptional activity of the p53:p73 chimeras or their ability to bind GR.

Conclusion
Our results indicate that both N- and C-terminal regions of p53 and p73 contribute to their regulation of GR. The differential ability of p53 and p73 to inhibit GR is due, in part, to differences in their N-terminal and C-terminal sequences.
Antiphospholipid reactivity against cardiolipin metabolites occurring during endothelial cell apoptosis
Authors: Alessandri Cristiano , Sorice Maurizio , Bombardieri Michele , Conigliaro Paola , Longo Agostina , Garofalo Tina , Manganelli Valeria , Conti Fabrizio , Esposti Mauro Degli , Valesini Guido 
Published: December 2006

AbstractWe have recently shown that cardiolipin (CL) and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. In this study, we investigate the immunoreactivity to CL derivatives occurring during endothelial apoptosis in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We compared the serum immunoreactivity to CL with that of its derivatives monolysocardiolipin (MCL), dilysocardiolipin (DCL), and hydrocardiolipin (HCL) by means of both enzyme-linked immunosorbent assay and thin-layer chromatography (TLC) immunostaining. In addition, we investigated the composition of phospholipid extracts from the plasma membrane of apoptotic endothelial cells and the binding of patients' sera to the surface of the same cells by using high-performance TLC and immunofluorescence analysis. The average reactivity to MCL was comparable with that of CL and significantly higher than that for DCL and HCL in patients studied, both in the presence or in the absence of beta2-glycoprotein I. Of relevance for the pathogenic role of these autoantibodies, immunoglobulin G from patients' sera showed an increased focal reactivity with the plasma membrane of endothelial cells undergoing apoptosis. Interestingly, the phospholipid analysis of these light membrane fractions showed an accumulation of both CL and MCL. Our results demonstrated that a critical number of acyl chains in CL derivatives is important for the binding of antiphospholipid antibodies and that MCL is an antigenic target with immunoreactivity comparable with CL in APS and SLE. Our finding also suggests a link between apoptotic perturbation of CL metabolism and the production of these antibodies.
Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages
Authors: Armani Chiara , Catalani Elisabetta , Balbarini Alberto , Bagnoli Paola , Cervia Davide 
Published: December 2006

AbstractSomatostatin (SRIF)-14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst1–sst5) is poorly understood in humans. In our study, we demonstrate that human macrophages, differentiated from PBMC-derived monocytes, express sst1 and sst2 mRNAs. sst1 and sst2 are mostly localized at the cell surface and display active binding sites. In particular, sst1/sst2 activation results in a weak internalization of sst1, and the sst2 internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogs SOM230 and KE108, but not by SRIF-14 or cortistatin-14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst1 and sst2 using CH-275 and SMS 201-995/L-779,976, respectively. Further, sst1- and sst2-mediated effects are reversed by the sst1 antagonist SRA-880 or the sst2 antagonist CYN 154806, respectively. CH-275, SMS 201-995, and L-779,976, but not SRIF-14, decrease mRNA expression and secretion of the MCP-1. In addition, SRIF-14, CH-275, SMS 201-995, and L-779,976 decrease IL-8 secretion, and they do not affect IL-8 mRNA expression. In contrast, SRIF-14 and sst1/sst2 agonists do not affect the secretion of matrix metalloproteinase-9. Collectively, our results suggest that the SRIF system, through sst1 and sst2, exerts mainly an immunosuppressive effect in human macrophages and may, therefore, represent a therapeutic window that can be exploited for the development of new strategies in pharmacological therapy of inflammation.
Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C
Authors: Byrnes Adriana A , Li Ding-You , Park Kiwon , Thompson Douglas , Mocilnikar Cathleen , Mohan Parvathi , Molleston Jean P , Narkewicz Michael , Zhou Huanfang , Wolf Stanley F , Schwarz Kathleen B , Karp Christopher L 
Published: December 2006

AbstractAlthough IFN-α forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN-α alone. The antiviral activities of IFN-α formed the rationale for its use in viral hepatitis. However, IFN-α and the other Type I IFNs are also pleiotropic immune regulators. Type I IFNs can promote IFN-γ production by activating STAT4 but can also inhibit production of IL-12, a potent activator of STAT4 and IFN-γ production. The efficacy of IFN-α in the treatment of hepatitis C may therefore depend in part on the balance of IFN-γ-inducing and IL-12-suppressing effects. We characterized the effects of pegylated IFN-α therapy for hepatitis C on the capacity of patients’ PBMC to produce IL-12 and IFN-γ ex vivo. Cells from patients with a sustained virological response to therapy had significantly greater levels of IFN-α-driven IFN-γ production prior to treatment than those from nonresponding patients. No differences in pretreatment IL-12 productive capacity were seen between patient groups. However, therapy with IFN-α led to suppression of inducible IL-12 production throughout the course of therapy in both groups of patients.
The Protective Effect of Tribulus terrestris in Diabetes
Authors: AMIN AMR , LOTFY MOHAMED , SHAFIULLAH MOHAMED , ADEGHATE ERNEST 
Published: December 2006

Abstract:
Tribulus terrestris L (TT) is used in the Arabic folk medicine to treat various diseases. The aim of this article was to investigate the protective effects of TT in diabetes mellitus (DM). Diabetes is known to increase reactive oxygen species (ROS) level that subsequently contributes to the pathogenesis of diabetes. Rats were divided into six groups and treated with either saline, glibenclamide (Glib), or TT for 30 days. Rats in group 1 were given saline after the onset of streptozotocin (STZ)‐induced diabetes; the second diabetic group was administered Glib (10 mg/kg body weight). The third diabetic group was treated with the TT extract (2 g/kg body weight), while the first, second, and third nondiabetic groups were treated with saline solution, Glib, and TT extract, respectively. At the end of the experiment, serum and liver samples were collected for biochemical and morphological analysis. Levels of serum alanine aminotransferase (ALT) and creatinine were estimated. In addition, levels of malondialdehyde (MDA) and reduced glutathione (GSH) were assayed in the liver. The tested TT extract significantly decreased the levels of ALT and creatinine in the serum (P < 0.05) in diabetic groups and lowered the MDA level in liver (P < 0.05) in diabetic and (P < 0.01) nondiabetic groups. On the other hand, levels of reduced GSH in liver were significantly increased (P < 0.01) in diabetic rats treated with TT. Histopathological examination revealed significant recovery of liver in herb‐treated rats. This investigation suggests that the protective effect of TT for STZ‐induced diabetic rats may be mediated by inhibiting oxidative stress.
The Relative Contributions of Aging, Health, and Lifestyle Factors to Serum Testosterone Decline in Men
Authors: Travison Thomas G. , Araujo Andre B. , Kupelian Varant , O’Donnell Amy B. , McKinlay John B. 
Published: December 2006

AbstractContext: Although it is known that serum testosterone (T) concentrations decline with age, the relative contributions of changes in health and lifestyle to that decline have not been adequately assessed.Objective: The objective of this study was to establish the relative importance of aging, health, and lifestyle in contributing to male T decline.Design: A prospective cohort study of health and endocrine functioning in randomly selected men with a baseline visit (T1, 1987–1989) and two follow-up visits (T2, 1995–1997; T3, 2002–2004) was conducted.Setting: An observational study of men residing in greater Boston, Massachusetts, was conducted.Participants: Participants included 1667 men aged 40 to 70 at baseline; follow-up was conducted on 947 (57%) and 584 (35%) at T2 and T3, respectively.Main Outcome Measures: Main outcome measures included total serum T, calculated free T (FT), and SHBG.Results: There were substantial declines in total serum T and FT levels associated with aging alone. However, many health and lifestyle changes were associated with accelerated decline. A 4- to 5-kg/m2 increase in body mass index or loss of spouse was associated with declines in total serum T comparable to that associated with approximately 10 yr of aging. Results were similar for FT, but fewer factors were associated with SHBG after age was taken into account.Conclusions: Both chronological aging and changes in health and lifestyle factors are associated with declines in serum T. Comorbidities and lifestyle influences may be as strongly associated with declining T levels as is aging itself over the short- to midterm. These results suggest the possibility that age-related hormone decline may be decelerated through the management of health and lifestyle factors.