bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas
Authors: Honma Keiichiro , Tsuzuki Shinobu , Nakagawa Masao , Tagawa Hiroyuki , Nakamura Shigeo , Morishima Yasuo , Seto Masao 
Published: July 2009

AbstractThe constitutive activation of nuclear factor-κB (NF-κB) has been implicated in tumorigenesis of lymphoid malignancies. We have previously shown that chromosome 6q was frequently deleted in ocular marginal zone B-cell lymphoma and identified TNFAIP3/A20, a negative regulator of NF-κB pathways, as the primary target for 6q deletion. In the study reported here, we extended the analysis to other subsets of non-Hodgkin lymphomas and found that A20 is frequently deleted in mantle cell lymphoma and diffuse large B-cell lymphoma. Importantly, A20 promoter methylation or gene mutation is also frequently detected in these lymphomas, raising the possibility that inactivation of A20 may be involved in lymphomagenesis. To address this question, we conducted overexpression experiments in lymphoma cell lines with A20 deletion and down-regulated expression of A20 with an siRNA technique in Epstein-Barr virus–infected lymphoblastoid cell lines. These experiments found that overexpression of A20 induced apoptosis and silencing of A20 was associated with resistance to apoptosis and enhanced clonogenicity. The cells with down-regulated A20 exhibited enhanced NF-κB activities, which may account for the observed effects. These results indicate that our study provides a novel insight into molecular mechanisms leading to lymphoma and that specific targeting of NF-κB pathways may be advantageous for treatment.
Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice
Authors: Chitu Violeta , Ferguson Polly J. , de Bruijn Rosalie , Schlueter Annette J. , Ochoa Luis A. , Waldschmidt Thomas J. , Yeung Yee-Guide , Stanley E. Richard 
Published: July 2009

AbstractThe mouse Lupo (I282N) mutation in proline-serine-threonine phosphatase–interacting protein 2 (PSTPIP2) leads to reduced expression of PSTPIP2 that is associated with a macrophage-mediated autoinflammatory disease. Another mutation in PSTPIP2, L98P, termed chronic multifocal osteomyelits (cmo), leads to a disease in mice that resembles chronic recurrent multifocal osteomyelits in humans. The cellular basis of cmo disease was investigated. cmo disease develops independently of lymphocytes and is cured by bone marrow transplantation. Macrophages, mast cells, and osteoclasts from cmo mice fail to express detectable PSTPIP2 protein. Asymptomatic Pstpip2cmo/cmo mice have increased circulating levels of macrophage inflammatory protein 1-α and interleukin-6, and their macrophages exhibit increased production of these inflammatory mediators, which is normalized by retroviral expression of wild-type PSTPIP2. Spleens of asymptomatic cmo mice contain increased numbers of macrophage precursors, and cmo mice mobilize more macrophage precursors in response to a sterile inflammatory stimulus. Signal transducer and activator of transcription 1 is elevated in cmo splenic macrophages, which also exhibit increased colony-stimulating factor-1–stimulated proliferation and increased extracellular signal-regulated kinase 1/2 phosphorylation. PSTPIP2 overexpression in macrophages leads to the opposite phenotype. Thus, PSTPIP2 deficiency causes both an expansion of macrophage progenitors and increased responsiveness of mature macrophages to activating stimuli, which together prime the organism for exaggerated and sustained responses leading to autoinflammatory disease.
Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose
Authors: Pulsipher Michael A. , Chitphakdithai Pintip , Logan Brent R. , Leitman Susan F. , Anderlini Paolo , Klein John P. , Horowitz Mary M. , Miller John P. , King Roberta J. , Confer Dennis L. 
Published: July 2009

AbstractWe report outcomes of 932 recipients of unrelated donor peripheral blood stem cell hematopoietic cell transplantation (URD-PBSC HCT) for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome enrolled on a prospective National Marrow Donor Program trial from 1999 through 2003. Preparative regimens included myeloablative (MA; N = 611), reduced-intensity (RI; N = 160), and nonmyeloablative (NMA; N = 161). For MA recipients, CD34+ counts greater than 3.8 × 106/kg improved neutrophil and platelet engraftment, whereas improved overall survival (OS) and reduced transplant-related mortality (TRM) were seen for all preparative regimens when CD34+ cell doses exceeded 4.5 × 106/kg. Higher infused doses of CD34+ cell dose did not result in increased rates of either acute or chronic graft-versus-host disease (GVHD). Three-year OS and disease-free survival (DFS) of recipients of MA, RI, and NMA approaches were similar (33%, 35%, and 32% OS; 33%, 30%, and 29% DFS, respectively). In summary, recipients of URD-PBSC HCT receiving preparative regimens differing in intensity experienced similar survival. Higher CD34+ cell doses resulted in more rapid engraftment, less TRM, and better 3-year OS (39% versus 25%, MA, P = .004; 38% versus 21% RI/NMA, P = .004) but did not increase the risk of GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00785525.
The role of chemokine receptors in acute lung allograft rejection
Authors: Geleff S. , Draganovici D. , Jaksch P. , Segerer S. 
Published: July 2009

Recruitment of inflammatory cells to vascularised allografts is a hallmark of rejection, and paves the way for chronic allograft injury. Chemokines play pivotal roles in the directed movement of leukocytes. Herein, we define the distribution of chemokine receptors for the most common cell types during human lung allograft rejection as a prerequisite for therapeutic interventions.Immunohistochemistry was performed on lung allograft biopsies from 54 patients for the chemokine receptors CCR5, CXCR3 and CXCR1 and the Duffy antigen/receptor for chemokines (DARC).Perivascular infiltrates in acute lung rejection are composed of subsets of mononuclear cells expressing the chemokine receptors CXCR1, CXCR3 and CCR5. DARC-positive small vessels and capillary vessels were associated with sites of inflammation and their number was increased during episodes of acute lung rejection. DARC expression correlated with an increase in interstitial CCR5-positive T-cells and CXCR1-positive leukocytes. Leucokytic infiltrates in bronchial/bronchiolar rejection express CXCR1 and CXCR3.This is the first study that demonstrates an induction of the chemokine binding protein DARC at sites of acute human lung allograft rejection. Co-localisation with the chemokine receptors CXCR1 and CCR5 may indicate a role for DARC expression during leukocyte adhesion and interstitial infiltration.
Relationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV infection
Authors: Leidl L. , Mayanja-Kizza H. , Sotgiu G. , Baseke J. , Ernst M. , Hirsch C. , Goletti D. , Toossi Z. , Lange C. 
Published: July 2009

Infection with HIV is the greatest risk factor for tuberculosis (TB) in Africa. Tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube (QFT-G-IT) and T-Spot.TB assays were performed in newly diagnosed HIV-infected individuals with and without active TB and in HIV-uninfected subjects at a university outpatient clinic in Kampala, Uganda.A total of 135 individuals were enrolled: 109 with a new diagnosis of HIV-1 infection but no active TB, 19 with HIV-1 infection and active TB, and seven HIV-uninfected healthy subjects. In control subjects immune responses were positive in 57.2% by TST and in 100% by at least one interferon-γ release assay.In HIV-1 infected patients without active TB, induration in the TST (mm) (rho = 0.41, p-value <0.0001) and concentration of interferon (IFN)-γ in the QFT-G-IT tube withMycobacterium tuberculosis-specific antigens (rho = 0.38; p = 0.0001) were negatively correlated to numbers of circulating CD4+ T-cells, while numbers of IFN-γ producing cells (rho = 0.03–0.13; p-value = 0.21–0.77) and frequencies of positive test results for the T-Spot.TB test among groups of patients with different levels of immunodeficiency remained constant (p-value = 0.46).In HIV-1 infection, TST and QFT-G-IT immune responses are both strongly related to the degree of immunodeficiency, while results of the T-Spot.TB are independent of the level of CD4+ T-cell depletion.
A randomised controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea
Authors: Lam J. C. M. , Lam B. , Yao T. J. , Lai A. Y. K. , Ooi C. G. , Tam S. , Lam K. S. L. , Ip M. S. M. 
Published: July 2009

The effects of treatment of obstructive sleep apnoea (OSA) on glucose metabolism have been investigated previously with conflicting results. This study evaluated the impact of nasal continuous positive airway pressure (nCPAP) treatment of OSA on insulin sensitivity.Males with moderate/severe OSA and no significant comorbidity were randomised to a therapeutic or sham nCPAP treatment group for 1 week and then reassessed. Those who received therapeutic nCPAP were further evaluated at 12 weeks. Insulin sensitivity (Kitt) was estimated by the short insulin tolerance test. Other evaluations included blood pressure, metabolic profile, urinary catecholamines and intra-abdominal fat.In total, 61 Chinese subjects were randomised. 31 subjects receiving therapeutic nCPAP showed an increase in Kitt(6.6±2.9 to 7.6±3.2 %·min−1; p = 0.017), while the 30 patients on sham CPAP had no significant change, and the changes in Kittwere different between the two groups (p = 0.022). At 12 weeks, improvement in Kittwas seen in 20 subjects with BMI ≥25 kg·m−2(median (interquartile range) 28.3 (26.6–31.5); p = 0.044), but not in the nine subjects with BMI<25 kg·m−2, or the entire group.The findings indicate that therapeutic nCPAP treatment of OSA for 1 week improved insulin sensitivity in nondiabetic males, and the improvement appeared to be maintained after 12 weeks of treatment in those with moderate obesity.
The impact of time on the systemic inflammatory response in pneumococcal pneumonia
Authors: Calbo E. , Alsina M. , Rodríguez-Carballeira M. , Lite J. , Garau J. 
Published: July 2009

The aim of our study was to analyse the impact of time from onset of symptoms on the systemic cytokine concentrations in patients with pneumococcal pneumonia.Adults with severe pneumococcal pneumonia were prospectively included. At admission, vital signs, time from onset of pneumonia symptoms and circulating levels of C-reactive protein (CRP), serum amyloid A (SAA), tumour necrosis factor (TNF)-α, and interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-1ra were recorded.32 patients were included; 13 patients had <48 h of evolution and 19 patients had been sick for >48 h. The group with a longer time of evolution presented higher plasmatic levels of TNF-α (19.1±8.5versus35.5±26 pg·mL−1), fibrinogen (6±1.8versus9±2); CRP (130±85versus327±131) and SAA (678±509versus984±391). Concentrations of TNF-α were associated with the presence of bacteraemia, initial blood pressure <90 mmHg and with a lower oxygen saturation at admission. Likewise, TNF-α levels were correlated with concentrations of IL-1β (r = 0.49), IL-6 (r = 0.41) and IL-8 (r = 0.40).In pneumococcal pneumonia, patients with a longer time of evolution presented with higher levels of pro-inflammatory cytokines and a higher expression of acute phase proteins, suggesting a sustained release of pneumococcal antigens over time.
Rituximab-induced lung disease: a systematic literature review
Authors: Lioté H. , Lioté F. , Séroussi B. , Mayaud C. , Cadranel J. 
Published: July 2009

The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab.A systematic literature review was performed on English-language reports in PubMed until September 2008.Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease.Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.
Genetic association study ofCYP1A1polymorphisms identifies risk haplotypes in nonsmall cell lung cancer
Authors: Wright C. M. , Larsen J. E. , Colosimo M. L. , Barr J. J. , Chen L. , McLachlan R. E. , Yang I. A. , Bowman R. V. , Fong K. M. 
Published: July 2009

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association ofCYP1A1gene polymorphisms and haplotypes with lung cancer risk.A case–control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate threeCYP1A1variants,CYP1A1*2A(rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)),CYP1A1*2C(rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) andCYP1A1*4(rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods.TheCYP1A1*2AandCYP1A1*2Cvariants were significantly over-represented in NSCLC cases compared with controls, whereas theCYP1A1*4variant was under-represented.CYP1A1haplotypes (in allele orderCYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population.The present study has identified risk haplotypes forCYP1A1in NSCLC and confirmed thatCYP1A1polymorphisms are a minor risk factor for NSCLC.
A novel Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) grafted Polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study
Authors: Shi Shuai , Guo QingFa , Kan Bing , Fu ShaoZhi , Wang XiuHong , Gong ChangYang , Deng HongXin , Luo Feng , Zhao Xia , Wei YuQuan , Qian ZhiYong 
Published: July 2009

Abstract

Background
Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection in vitro. However, its in vivo application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.

Results
Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-g-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-g-PEI was characterized by 1H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-g-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-g-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.

Conclusion
The cytotoxicity and in vitro transfection study indicated that PCFC-g-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).
Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR
Authors: Raynor Michael P , Stephenson Sally-Anne , Pittman Kenneth B , Walsh David CA , Henderson Michael A , Dobrovic Alexander 
Published: July 2009

Abstract

Introduction
The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells.

Results
Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients.
Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08).

Conclusion
Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.
17β-Estradiol at Low Concentrations Acts through Distinct Pathways in Normal Versus Benign Prostatic Hyperplasia-Derived Prostate Stromal Cells
Authors: Park Irwin I. , Zhang Qiang , Liu Victoria , Kozlowski James M. , Zhang Ju , Lee Chung 
Published: July 2009

Abstract
The aim of this study was to identify differential responses to low concentrations of 17β-estradiol (E2) in primary stromal cell cultures derived from either normal organ donors or benign prostatic hyperplasia or hypertrophy (BPH) specimens. Furthermore, we sought to identify the potential mechanism of E2 action in these cell types, through either a genomic or nongenomic mechanism. We initially treated stromal cells derived from five normal prostates or five BPH specimens with low concentrations of E2 (0.001–1.0 nm) and analyzed their growth response. To determine whether genomic or nongenomic pathways were involved, we performed studies using specific estrogen receptor antagonists to confirm transcriptional activity or MAPK inhibitors to confirm the involvement of rapid signaling. Results of these studies revealed a fundamental difference in the mechanism of the response to E2. In normal cells, we found that a nongenomic, rapid E2 signaling pathway is predominantly involved, mediated by G protein-coupled receptor-30 and the subsequent activation of ERK1/2. In BPH-derived prostate stromal cells, a genomic pathway is predominantly involved because the addition of ICI 182780 was sufficient to abrogate any estrogenic effects. In conclusion, prostate stromal cells respond to far lower concentrations of E2 than previously recognized or examined, and this response is mediated through two distinct mechanisms, depending on its origin. This may provide the basis for new insights into the causes of, and possible treatments for, BPH.
An Adiponectin-Like Molecule with Antidiabetic Properties
Authors: Sulpice Thierry , Prunet-Marcassus Bénédicte , Molveaux Cécile , Cani Patrice D. , Vitte Pierre-Alain , Graber Pierre , Dreano Michel , Burcelin Rémy 
Published: July 2009

Abstract
Adiponectin increases glucose transport, reduces inflammation, and controls vascular functions. Hence, we propose that treatment with a recombinant globular domain of adiponectin (rgAd110-244) has significant therapeutic potential to treat insulin resistance. Mice were fed for 3 months on a high-fat diet (HFD) to induce insulin resistance, diabetes, and moderate weight gain. The mice were first infused iv with different doses of rgAd110-244 (0.12, 0.4, and 1.2 μg/kg · min) for 5 h. Basal and insulin-sensitive glucose use rates were assessed by the use of a submaximal rate of insulin in the awake free-moving mouse. rgAd110-244 reduced, with dose dependence, epinephrine-induced hyperglycemia and HFD-induced insulin resistance by increasing whole-body glucose use (35% at the highest dose) and glycolysis rates. Similarly, the reduction of plasma free fatty acid concentrations by insulin was dramatically improved. Basal hepatic glucose production was unchanged by rgAd110-244 infusion. This acute rgAd110-244 treatment improved glucose homeostasis and was associated with an increased content of muscle phospho-Akt, glycogen synthase kinase-3β, and AMP-activated kinase. Second, HFD mice were chronically treated with sc rgAd110-244 injections (10, 30, and 100 μg/kg). Fasting glycemia and insulin-sensitive glucose use were improved by rgAd110-244 at the highest dose at completion of the treatment, with concomitant reduction in body weight gain. We here show for the first time that a recombinant adiponectin fragment (110-244 amino acids called rgAd110-244) is able to treat insulin-resistant diabetes. Our results strongly suggest further pharmacological investigation of rgAd110-244 with the objective of developing a new treatment of insulin-resistant diabetes.
Absence of Estrogen Receptor-Related-α Increases Osteoblastic Differentiation and Cancellous Bone Mineral Density
Authors: Delhon I. , Gutzwiller S. , Morvan F. , Rangwala S. , Wyder L. , Evans G. , Studer A. , Kneissel M. , Fournier B. 
Published: July 2009

Abstract
The nuclear orphan receptor human estrogen receptor-related receptor (ERR)-α is implicated in bone metabolism. We studied the effect of ERRα silencing in human mesenchymal stem cells (hMSCs) during osteoblastogenesis. We found that ERRα silencing led to an increase of bone sialoprotein and a decrease of osteopontin mRNA levels, suggesting enhanced osteoblastic differentiation. This was confirmed by an increased ability of hMSCs to deposit calcium. Concomitantly, knockdown of ERRα inhibited adipogenesis, resulting in a decrease in adipocyte number and adipocyte marker gene expression. In line with a negative role of ERRα in bone metabolism, we found that adult female and male ERRα-deficient mice displayed a moderate increase in femoral cancellous bone volume and density. Osteoblast surface was increased and marrow fat volume decreased in these animals. Furthermore, ERRα-deficient osteoblasts displayed increased differentiation properties in vitro in line with our observations in hMSCs. In summary, we identified a role for ERRα in bone mass regulation by affecting osteoblastic differentiation.