bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Rapamycin on Mouse Chronic Lymphocytic Leukemia and the Development of Nonhematopoietic Malignancies in Eμ-TCL1 Transgenic Mice
Authors: Zanesi Nicola , Aqeilan Rami , Drusco Alessandra , Kaou Mohamed , Sevignani Cinzia , Costinean Stefan , Bortesi Laura , La Rocca Gaspare , Koldovsky Pavel , Volinia Stefano , Mancini Rita , Calin George , Scott Charles P. , Pekarsky Yuri , Croce Carlo M. 
Published: January 2006

Abstract
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the world. The TCL1 gene, responsible for prolymphocytic T cell leukemia, is also overexpressed in human B cell malignancies and overexpression of the Tcl1 protein occurs frequently in CLL. Aging transgenic mice that overexpress TCL1 under control of the μ immunoglobulin gene enhancer, develop a CD5+ B cell lymphoproliferative disorder mimicking human CLL and implicating TCL1 in the pathogenesis of CLL. In the current study, we exploited this transgenic mouse to investigate two different CLL-related issues: potential treatment of CLL and characterization of neoplasms that accompany CLL. We successfully transplanted CLL cells into syngeneic mice that led to CLL development in the recipient mice. This approach allowed us to verify the involvement of the Tcl1/Akt/mTOR biochemical pathway in the disease by testing the ability of a specific pharmacologic agent, rapamycin, to slow CLL. We also showed that 36% of these transgenic mice were affected by solid malignancies, in which the expression of the Tcl1 protein was absent. These findings indicate that other oncogenic mechanism(s) may be involved in the development of solid tumors in Eμ-TCL1 transgenic mice. (Cancer Res 2006: 66(2): 915–20)
Altered Expression and Localization of Creatine Kinase B, Heterogeneous Nuclear Ribonucleoprotein F, and High Mobility Group Box 1 Protein in the Nuclear Matrix Associated with Colon Cancer
Authors: Balasubramani Manimalha , Day Billy W. , Schoen Robert E. , Getzenberg Robert H. 
Published: January 2006

Abstract
Identification of biomarkers could lead to the development of effective screening tests for colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in colon cancer. In an effort to characterize these biomarkers, protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGB1) isoforms. To determine the expression of these proteins in colon cancer, expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon tumors, respectively. hnRNP F had a higher frequency of expression than CKB in premalignant polyps. With the establishment of differential expression of the proteins in colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high protein levels of hnRNP F in colon tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis. These results suggest an involvement of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F is a potential marker for colorectal cancer progression. (Cancer Res 2006; 66(2): 763-9)
Interaction of Nε(carboxymethyl)lysine- and methylglyoxalmodified albumin with endothelial cells and macrophages
Authors: Lieuw-a-Fa Mariska , Engelse Marten , van Hinsbergh Victor , Schalkwijk Casper 
Published: January 2006

SummaryIn diabetes mellitus an increased risk exists for vascular complications. A role for advanced glycation endproducts (AGEs) in the acceleration of vascular disease has been suggested. Nε(carboxymethyl)lysine (CML)- and methylglyoxal (MGO)-modified proteins have been identified as majorAGEs. The interaction of these AGEs with the human endothelial cells and macrophages was studied. Changes in adhesion molecule expression, i. e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by cell-bound Elisa on human endothelial cells after incubation with CML-modified albumin and MGO-modified albumin. The presence of the full-length receptor of AGEs (RAGE) and splice variants of RAGE was determined by specific RT-PCR. In addition, binding studies were performed with CML- and MGOmodified albumin to endothelial cells and P388D1 macrophages. We demonstrated that CML-albumin or MGO-albumin did not induce activation of endothelial cells as measured by the expression of adhesion molecules, while, under the same conditions, TNF-α did. No specific binding of CML-albumin and MGO-albumin on these cells was found. In contrast to endothelial cells, a specific binding of MGO-albumin to P388D1 macrophages was demonstrated, which could be competed by ligands of scavenger receptors. In human umbilical vein and microvascular endothelial cells we found the N-truncated and C-truncated splice variants of RAGE.In conclusion, under our experimental conditions no CML- or MGO-albumin-induced increase in adhesion molecule expression was found on endothelial cells. In agreement with this, no binding of these AGEs was found to endothelial cells. The existence of splice variants of RAGE in endothelial cells might explain the lack of interaction of extracellular AGEs with these cells.
Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina
Authors: Berg Oliver , Heimann Axel , Münzel Thomas , Vahl Christian-Friedrich , Kempski Oliver , Darius Harald , Bierbach Benjamin , Horstick Georg 
Published: January 2006

SummaryApplication of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore, the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0.1 mg/kg or5 mg/kg), aspirin (1 mg/kg or 7 mg/kg) or LDC (0.1 mg/kg clopidogrel and 1 mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min. CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, −48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg, −65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0.1 mg/kg) plus aspirin (1 mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (−70%, p<0.05). Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.
Two sibling cases of hydrops fetalis due to alloimmune anti-CD36 (Naka) antibody
Authors: Cho Kazutoshi , Chiba Hitoshi , Azuma Hiroshi , Mochizuki Toshiko , Yamaguchi Miki , Sato Shin-ichiro , Ikeda Hisami , Yamada Hideto , Minakami Hisanori , Ariga Tadashi , Kobayashi Kunihiko , Okajima Satoru 
Published: January 2006

SummaryTwo female sibling cases, who were born to a CD36 deficient mother, were presented with Coombs’ test-negative hydrops. The alloimmune anti-CD36 (Naka) antibody was accidentally found in the mother’s serum after an episode of anaphylactic shock with thrombocytopenia, which occurred in an individual receiving fresh frozen plasma prepared from the mother’s donated blood. The mother was then diagnosed as having type II CD36 deficiency, lacking CD36 on both platelets and monocytes, while both of her daughters were CD36 positive. Analyses of the CD36 gene revealed that the mother was a compound heterozygote for the CD36 gene mutation with a novel C→T transition at nt 1366 in exon 12, corresponding to Arg386Trp, and a known 12bp deletion at nt 1438–1449 in exon 13. On the other hand, both patients, who showed half the normal level of CD36 on platelets and monocytes, were heterozygote with one mutation at Arg386Trp. The anti-CD36 antibody in the mother seemed to be responsible for the hydrops fetalis observed in her daughters, because the IgG isolated from the mother’s serum showed suppressive effects on the CFU-E colony formation of CD34+ cells from a control donor. This is the first case report of hydrops fetalis caused by an alloimmune anti-CD36 antibody.
Combined genetic profiles of components and regulators of the vitamin K-dependent γ-carboxylation system affect individual sensitivity to warfarin
Authors: Vecsler Manuela , Loebstein Ronen , Almog Shlomo , Kurnik Daniel , Goldman Boleslav , Halkin Hillel , Gak Eva 
Published: January 2006

SummaryWe examined the influence of combined genotypes on interindividual variability in warfarin dose-response. In 100 anticoagulated patients we quantified the effects of polymorphisms in: CYP2C9, VKORC1, calumenin (CALU), γ-glutamyl carboxylase (GGCX) and microsomal epoxide hydrolase (EPHX1) on warfarin dose requirements. The G1542C VKORC1 polymorphism was associated with decreased warfarin doses in the heteroand homozygous mutant patients (21% and 50% lower, respectively; p<0.0001). Warfarin daily dose was predominantly determined by VKORC1 and CYP2C9 genotypes (partial r2= 0.21; 0.20, respectively). Together with age and body weight, these two genotypes explained 63% of the dose variance. A single patient, homozygous for G11A CALU mutant allele, required an excep tionally high warfarin dose (20mg/day) and the prevalence of heterozygous 11A allele carriers in the upper 10th dose percentile was significantly higher (0.27 vs. 0.18, p<0.02). Combined genotype analysis revealed that CYP2C9 andVKORC1 wild type and CALU mutant patients required the highest warfarin doses (7. 8±1. 5mg/day; n=9) as compared to the CYP2C9 and VKORC1 mutant and CALU wild type genotypes (2. 8±0. 3mg/day; n=18; p<0.01). The odds ratio for doses <3mg/day was 5. 9 (1.9–18. 4) for this genotype. Compound genetic profiles comprising VKORC1, CALU and CYP2C9 improve categorization of individual warfarin dose requirements in more than 25% of patients at steady-state anticoagulation.
Endothelial cells express a matrix protein which binds activated factor XII in a zinc-independent manner
Authors: Schousboe Inger 
Published: January 2006

SummaryRecent studies have shown that peptides identified as surface binding regions of high molecular mass kininogen (HK) and factor XII (FXII) inhibit the Zn2+-dependent binding of FXII to confluent layers of human umbilical vein endothelial cells (HUVEC). This indicates that negatively charged FXII binding surfaces, such as sulfatides and dextran sulfate, may interfere with the binding of FXII to confluent layer of HUVEC. Upon investigating this hypothesis it was unexpectedly found that sulfatides enhanced a specific binding of FXII to a matrix protein expressed during growth of the endothelial cells and that this binding was independent of the presence of Zn2+. The function of sulfatides was partly to minimize nonspecific electrostatic binding and partly to induce and enhance autoactivation of FXII generating αFXIIa. Western blot analysis of the extracts of the matrix incubated with FXII and sulfatides showed that the binding was specific for αFXIIa. The dissociation constant for binding αFXIIa was 12. 8 ± 0. 4 nM (n=4). The binding of αFXIIa to ECM was mapped to the heavy chain as no binding was observed of the light chain containing the catalytic domain. HK, which previously has been shown to completely abolish the Zn2+-dependent binding of FXII to confluent layers of HUVEC, did not inhibit the binding of αFXIIa to the matrix but sulfatides enhanced binding of FXII to ECM. This suggests that HK interferes with the binding of FXII to sulfatides and thereby the autoactivation of FXII. Trypsin treatment of the matrix protein completely abolished the binding, and fibronectin but not laminin was found to bea suitable target. The binding of activated FXII to the ECM suggests that FXIIa may bea modulator of cellular adhesion, migration and vascularization.
Long term influence of regular intake of high dose n-3 fatty acids on CD40-ligand, pregnancy-associated plasma protein A and matrix metalloproteinase-9 following acute myocardial infarction
Authors: Brügger-Andersen Trygve , Hetland Øyvind , Grundt Heidi , Nilsen Dennis , Aarsetøy Hildegunn 
Published: January 2006

SummaryPregnancy-associated plasma protein A (PAPP-A) and matrix metalloproteinase 9 (MMP-9), both zinc-binding endopeptidases, are abundantly expressed in ruptured and eroded plaques in patients with acute coronary syndromes (ACS).The adhesion molecule CD-40 ligand (CD40L), expressed on activated platelets and T-lymphocytes, can activate metalloproteinases and thereby promote plaque-rupture. N-3 fatty acids, through their anti-inflammatory and anti-thrombotic properties,might reduce the levels of these proatherosclerotic markers and thereby the development of ACS. 300 patients were randomized on day4 to 6 following an acute myocardial infarction (MI) to receive either 4g of n-3 fatty acids or a similar daily dose of corn oil for at least one year.We compared levels of PAPP-A, MMP-9 and sCD-40 L at baseline and 12 months in each group, and also looked for inter-group changes. In the omega-3 group, the median level of PAPP-A rose from 0.47 mU/l to 0.56 mU/l (p < 0.001). In the same group, sCD-40 L decreased froma mean baseline value of 5.19 ng/ml to 2.45 ng/ml (p < 0.001) and MMP-9 decreased nonsignificantly from 360.50 ng/ml to 308.00 ng/ml. Corresponding values for the corn oil group were 0.54 mU/l to 0.59 mU/l for PAPP-A (p= 0.007), 5.27 ng/ml to 2.84 ng/ml for sCD-40 L (p< 0.001) and 430.00 ng/ml to 324.00 ng/ml for MMP-9 (p=ns), respectively. In conclusion; both interventions resulted in a significant rise in PAPP-A, a significant decrease in sCD40L and a non-significant decrease in MMP-9 after 12 months of treatment in MI survivors. No inter-group differences were noted.
Differential expression of tissue factor mRNA and protein expression in murine sepsis
Authors: de Waard Vivian , Hansen Hjalmar , Spronk Henri , Timmerman Janneke , Pannekoek Hans , Florquin Sandrine , Reitsma Pieter , ten Cate Hugo 
Published: January 2006

SummaryTissue factor (TF) is a transmembrane protein, which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of endotoxin (lipopolysaccharide, LPS)-mediated endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validateda rabbit anti-murine TF peptide antiserum to localize TF protein in a murine sepsis model. TF protein distribution was compared to localization of TF mRNA and fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPSmediated TF mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of endotoxemia. In the spleen, however, TF mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF protein in the same area. The clusters of TF-protein positive cells in the spleen are predominantly granulocytes, but no TF mRNA expression was observed within these cells. Based on these observations and the presence of TF-protein positive granulocytes after splenectomy, we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate fibrin formation or to induce pronflammatory gene expression upon interaction with factor VIIa.
Increased plasma prothrombin concentration in cirrhotic patients with portal vein thrombosis and prothrombin G20210A mutation
Authors: Guardascione Maria , Ames Paul , Margaglione Maurizio , Iannaccone Luigi , Brancaccio Vincenzo , Balzano Antonio , Amitrano Lucio 
Published: January 2006

SummaryIt was the aim of the present study to investigate factor II levels in liver cirrhosis (LC) patients with portal vein thrombosis (PVT) carrying the heterozygous G20210A prothrombin (PT) mutation. Plasma concentrations of factor II, VII, X, V, protein C (PC) total protein S (tPS) antithrombin (AT) and D-dimers (DD) were measured in 13 LC patients with PVT heterozygous for PT G20210A, in 13 LC patients with PVT without PT G20210A and in 13 LC controls matched by age, sex and Child-Pugh score. Crude factor II and factor II/DD ratio were highest in LC patients with PVT heterozygous for PT G20210A (p=0.03 and p=0.02 respectively). The factor II/PC ratio, expression of a procoagulant/anticoagulant imbalance was highest in the same group (p=0.0008). Plasma factor II levels are elevated in LC patients heterozygous for PT G20210A and may favour PVT.
The serpin proteinase inhibitor 8: An endogenous furin inhibitor released from human platelets
Authors: Leblond Julie , Laprise Marie-Hélène , Gaudreau Simon , Grondin Francine , Kisiel Walter , Dubois Claire 
Published: January 2006

SummaryThe cornerstone of hemostasis is the ability of the organism to limit the enzymatic processes involved, thereby avoiding thrombosis. For this, anticoagulant systems in place involve serpins, such as PAI-1 and antithrombin III, which bind to their targeted serine proteases and limit their period of activity. We have previously identified the serine protease furin as a platelet-derived enzyme with an intrinsic role in platelet functions. We now report that furin enzymatic activity decreased rapidly following platelet activation, corresponding with the increase in formation of a high 180 M
r SDS-stable complex composed of furin and the PI8 serpin. PI8 is shown to be a platelet-derived constituent, synthesized by megakaryocytes and stored in platelets prior to its release. Immunoprecipitation and purification of the PI8-furin complex confirmed their direct interaction and indicates that one of the roles of PI8 is to inhibit furin enzymatic activity. Furthermore, our findings demonstrate the inhibitory capacity of exogenous PI8 in platelet aggregation assays. The finding that PI8 is released by platelets and controls functional responses suggests a role for this serpin in platelet-regulated pathophysiological responses.
Correlates of Return to Work for Breast Cancer Survivors
Authors: Bouknight Reynard R. , Bradley Cathy J. , Luo Zhehui 
Published: January 2006

Purpose To identify correlates of return to work for employed breast cancer survivors. Patients and Methods Patients included 416 employed women with newly diagnosed breast cancer identified from the Metropolitan Detroit Cancer Surveillance System. Patients were interviewed by telephone 12 and 18 months after diagnosis. Correlates of return to work at 12 and 18 months were identified using multivariate logistic regression. Results More than 80% of patients returned to work during the study period, and 87% reported that their employer was accommodating to their cancer illness and treatment. After adjusting for demographic characteristics, health status, cancer stage, treatment, and job type, heavy lifting on the job (odds ratio = 0.42; 95% CI, 0.18 to 0.99), perceived employer accommodation for cancer illness and treatment (odds ratio = 2.2; 95% CI, 1.03 to 4.8), and perceived employer discrimination because of a cancer diagnosis (odds ratio = 0.27; 95% CI, 0.10 to 0.71) were independently associated with return to work at 12 months after breast cancer diagnosis, and perceived employer accommodation (odds ratio = 2.3; 95% CI, 1.06 to 5.1) was independently associated with return to work at 18 months after breast cancer diagnosis. Conclusion A high percentage of employed breast cancer patients returned to work after treatment, and workplace accommodations played an important role in their return. In addition, perceived employer discrimination because of cancer was negatively associated with return to work for breast cancer survivors. Employers seem to have a pivotal role in breast cancer patients' successful return to work.
Risk of Selected Subsequent Carcinomas in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Bassal Mylène , Mertens Ann C. , Taylor Leslie , Neglia Joseph P. , Greffe Brian S. , Hammond Sue , Ronckers Cécile M. , Friedman Debra L. , Stovall Marilyn , Yasui Yutaka Y. , Robison Leslie L. , Meadows Anna T. , Kadan-Lottick Nina S. 
Published: January 2006

Purpose To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer. Patients and Methods Subsequent malignant neoplasm history was determined in 13,136 participants (surviving ≥ 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data. Results In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9). Conclusion Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.