bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct homeostatic requirements of CD4+ and CD4- subsets of Vα24-invariant natural killer T cells in humans
Authors: Baev Denis V. , Peng Xiao-hui , Song Liping , Barnhart Jerry R. , Crooks Gay M. , Weinberg Kenneth I. , Metelitsa Leonid S. 
Published: August 2004

AbstractCD1d-restricted Vα24-invariant natural killer T cells (iNKTs) are important in immunoregulation. CD4+ and CD4- iNKTs develop with similar frequencies in murine thymus and depend on interleukin-15 (IL-15) in periphery. However, homeostatic requirements of iNKTs have not been analyzed in humans. We evaluated thymic production, peripheral dynamics, and functional maturation of human iNKTs. CD4+ subset comprises 90% of iNKTs in mature thymocytes and cord blood (CB) but only 40% in adult blood. Using T-cell receptor excision circle (TREC) analysis, we directly measured in vivo replicative history of CD4+ and CD4- iNKT cells. Compared to CD4+, CD4- iNKTs contain fewer TRECs, express higher levels of IL-2Rβ, and proliferate with higher rate in response to IL-15. In contrast, CD4+ cells express higher levels of IL-7Rα and better respond to IL-7. Neither thymic nor CB iNKTs are able to produce cytokines unless they are induced to proliferate. Therefore, unlike in the mouse, human CD4+ iNKTs are mainly supported by thymic output and limited peripheral expansion, whereas CD4- cells undergo extensive peripheral expansion, and both subsets develop their functions in periphery. These findings reveal important differences in homeostatic requirements and functional maturation between murine and human iNKTs that are to be considered for clinical purposes.
CD157 is an important mediator of neutrophil adhesion and migration
Authors: Funaro Ada , Ortolan Erika , Ferranti Bruna , Gargiulo Lucia , Notaro Rosario , Luzzatto Lucio , Malavasi Fabio 
Published: August 2004

AbstractCD157, a glycosylphosphatidylinositol (GPI)–anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca2+ concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]–ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)–differentiated (CD157+/CD38-) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and β2 integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formyl-methionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation.
Mature myeloid dendritic cell subsets have distinct roles for activation and viability of circulating human natural killer cells
Authors: Münz Christian , Dao Tao , Ferlazzo Guido , de Cos Maria A. , Goodman Kiera , Young James W. 
Published: August 2004

AbstractNatural killer (NK) cells are important effectors of innate immunity. In contrast to many studies of interleukin-2 (IL-2)-activated NK cells, the physiologic requirements for stimulating resting NK cells have only recently received attention. Given the emerging variety of dendritic cell (DC) types and their division of labor for stimulating immunity, we compared the capacity of monocyte-derived DCs (moDCs) with that of CD34+ hematopoietic progenitor cell (HPC)-derived dermal-interstitial DCs (DDC-IDCs) and Langerhans cells (LCs) to stimulate resting NK cells. MoDCs, and to a lesser extent CD34+ HPC-derived DDC-IDCs, directly stimulate NK-cell proliferation, CD56 up-regulation, and cytotoxicity. LCs, on the contrary, require exogenous IL-2 or IL-12 to activate NK cells, but they can maintain resting NK-cell viability and sustain NK-cell proliferation induced by moDCs. LCs do not secrete bioactive IL-12p70 but do produce significantly higher concentrations of IL-15 and IL-18 than either of the other 2 DC types. Despite secretion of IL-15, LCs lack IL-15R-α for surface presentation of IL-15. This together with the deficiency of IL-12p70 undermines any direct NK-cell activation by LCs. Hence, the principal myeloid DCs differ in critical ways regarding the stimulation of NK and T lymphocytes and could be used or targeted accordingly in DC-based immunotherapies. (Blood. 2005;105:266-273)
Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity
Authors: Middendorp Sabine , Zijlstra A. J. Esther , Kersseboom Rogier , Dingjan Gemma M. , Jumaa Hassan , Hendriks Rudolf W. 
Published: August 2004

AbstractDuring B-cell development in the mouse, Bruton tyrosine kinase (Btk) and the adaptor protein SLP-65 (Src homology 2 [SH2] domain-containing leukocyte protein of 65 kDa) limit the expansion and promote the differentiation of pre-B cells. Btk is thought to mainly function by phosphorylating phospholipase Cγ2, which is brought into close proximity of Btk by SLP-65. However, this model was recently challenged by the identification of a role for Btk as a tumor suppressor in the absence of SLP-65 and by the finding that Btk function is partially independent of its kinase activity. To investigate if enzymatic activity is critical for the tumor suppressor function of Btk, we crossed transgenic mice expressing the kinase-inactive K430R-Btk mutant onto a Btk/SLP-65 double-deficient background. We found that K430R-Btk expression rescued the severe developmental arrest at the pre-B-cell stage in Btk/SLP-65 double-deficient mice. Moreover, K430R-Btk could functionally replace wild-type Btk as a tumor suppressor in SLP-65- mice: at 6 months of age, the observed pre-B-cell lymphoma frequencies were approximately 15% for SLP-65- mice, 44% for Btk/SLP-65-deficient mice, and 14% for K430R-Btk transgenic mice on the Btk/SLP-65-deficient background. Therefore, we conclude that Btk exerts its tumor suppressor function in pre-B cells as an adaptor protein, independent of its catalytic activity. (Blood. 2005;105:259-265)
A mechanism of airway injury in an epithelial model of mucociliary clearance
Authors: O'Brien Darryl W , Morris Melanie I , Ding Jie , Zayas J Gustavo , Tai Shusheng , King Malcolm 
Published: August 2004

AbstractWe studied the action of sodium metabisulphite on mucociliary transport in a frog palate epithelial injury model, hypothesizing that it may be useful for the study of mechanisms of airway injury. Sodium metabisulphite (MB) releases SO2 on contact with water. SO2 is a pollutant in automobile fumes and may play a role in the exacerbation of airway disease symptoms. We first investigated its effect on mucociliary clearance. MB 10-1 M, increased mucociliary clearance time (MCT) by 254.5 ± 57.3% of control values, (p < 0.001, n = 7). MB 10-4 and 10-2 M did not interfere with mucus clearance time compared to control values. In MB-treated frog palates, MCT did not return to control values after one hour (control, 97.3 ± 6.3% vs. MB, 140.9 ± 46.3%, p < 0.001, n = 7). Scanning EM images of epithelial tissue were morphometrically analyzed and showed a 25 ± 12% loss of ciliated cells in MB palates compared to controls with an intact ciliary blanket. Intact cells or groups of ciliated cells were found in scanning EM micrographs of mucus from MB-treated palates. This was associated with increased matrix metalloproteinase (MMP-9) activity in epithelial tissue and mucus. We suggest that the loss of ciliated cells as a result of MMP-9 activation prevented full recovery of MCT after MB 10-1 M. The mechanism of action may be on epithelial cell-cell or cell-matrix attachments leading to cell loss and a disruption of MCT. Further studies are warranted to determine whether this is an inflammatory mediated response or the result of a direct action on epithelial cells and what role this mechanism may play in the progression to chronic airway diseases with impaired mucociliary clearance.
The aminoguanidine carboxylate BVT.12777 activates ATP-sensitive K+ channels in the rat insulinoma cell line, CRI-G1
Authors: Kinsella Jackie M , Laidlaw Hilary A , Tang Teresa , Harvey Jenni , Sutherland Calum , Ashford Michael LJ 
Published: August 2004

Abstract
Background
3-guanidinopropionic acid derivatives reduce body weight in obese, diabetic mice. We have assessed whether one of these analogues, the aminoguanidine carboxylate BVT.12777, opens KATP channels in rat insulinoma cells, by the same mechanism as leptin.

Results
BVT.12777 hyperpolarized CRI-G1 rat insulinoma cells by activation of KATP channels. In contrast, BVT.12777 did not activate heterologously expressed pancreatic β-cell KATP subunits directly. Although BVT.12777 stimulated phosphorylation of MAPK and STAT3, there was no effect on enzymes downstream of PI3K. Activation of KATP in CRI-G1 cells by BVT.12777 was not dependent on MAPK or PI3K activity. Confocal imaging showed that BVT.12777 induced a re-organization of cellular actin. Furthermore, the activation of KATP by BVT.12777 in CRI-G1 cells was demonstrated to be dependent on actin cytoskeletal dynamics, similar to that observed for leptin.

Conclusions
This study shows that BVT.12777, like leptin, activates KATP channels in insulinoma cells. Unlike leptin, BVT.12777 activates KATP channels in a PI3K-independent manner, but, like leptin, channel activation is dependent on actin cytoskeleton remodelling. Thus, BVT.12777 appears to act as a leptin mimetic, at least with respect to KATP channel activation, and may bypass up-stream signalling components of the leptin pathway.
Opposite role of Bax and BCL-2 in the anti-tumoral responses of the immune system
Authors: Bougras Gwenola , Cartron Pierre-François , Gautier Fabien , Martin Stéphane , LeCabellec Marité , Meflah Khaled , Gregoire Marc , Vallette François M 
Published: August 2004

Abstract
Background
The relative role of anti apoptotic (i.e. Bcl-2) or pro-apoptotic (e.g. Bax) proteins in tumor progression is still not completely understood.

Methods
The rat glioma cell line A15A5 was stably transfected with human Bcl-2 and Bax transgenes and the viability of theses cell lines was analyzed in vitro and in vivo.

Results
In vitro, the transfected cell lines (huBax A15A5 and huBcl-2 A15A5) exhibited different sensitivities toward apoptotic stimuli. huBax A15A5 cells were more sensitive and huBcl-2 A15A5 cells more resistant to apoptosis than mock-transfected A15A5 cells (pCMV A15A5). However, in vivo, in syngenic rat BDIX, these cell lines behaved differently, as no tumor growth was observed with huBax A15A5 cells while huBcl-2 A15A5 cells formed large tumors. The immune system appeared to be involved in the rejection of huBax A15A5 cells since i) huBax A15A5 cells were tumorogenic in nude mice, ii) an accumulation of CD8+ T-lymphocytes was observed at the site of injection of huBax A15A5 cells and iii) BDIX rats, which had received huBax A15A5 cells developed an immune protection against pCMV A15A5 and huBcl-2 A15A5 cells.

Conclusions
We show that the expression of Bax and Bcl-2 controls the sensitivity of the cancer cells toward the immune system. This sensitization is most likely to be due to an increase in immune induced cell death and/or the amplification of an anti tumour immune response
What does my patient's coronary artery calcium score mean? Combining information from the coronary artery calcium score with information from conventional risk factors to estimate coronary heart disease risk
Authors: Pletcher Mark J , Tice Jeffrey A , Pignone Michael , McCulloch Charles , Callister Tracy Q , Browner Warren S 
Published: August 2004

Abstract
Background
The coronary artery calcium (CAC) score is an independent predictor of coronary heart disease. We sought to combine information from the CAC score with information from conventional cardiac risk factors to produce post-test risk estimates, and to determine whether the score may add clinically useful information.

Methods
We measured the independent cross-sectional associations between conventional cardiac risk factors and the CAC score among asymptomatic persons referred for non-contrast electron beam computed tomography. Using the resulting multivariable models and published CAC score-specific relative risk estimates, we estimated post-test coronary heart disease risk in a number of different scenarios.

Results
Among 9341 asymptomatic study participants (age 35–88 years, 40% female), we found that conventional coronary heart disease risk factors including age, male sex, self-reported hypertension, diabetes and high cholesterol were independent predictors of the CAC score, and we used the resulting multivariable models for predicting post-test risk in a variety of scenarios. Our models predicted, for example, that a 60-year-old non-smoking non-diabetic women with hypertension and high cholesterol would have a 47% chance of having a CAC score of zero, reducing her 10-year risk estimate from 15% (per Framingham) to 6–9%; if her score were over 100, however (a 17% chance), her risk estimate would be markedly higher (25–51% in 10 years). In low risk scenarios, the CAC score is very likely to be zero or low, and unlikely to change management.

Conclusion
Combining information from the CAC score with information from conventional risk factors can change assessment of coronary heart disease risk to an extent that may be clinically important, especially when the pre-test 10-year risk estimate is intermediate. The attached spreadsheet makes these calculations easy.
Regulation of inflammatory responses by activated protein C: the molecular mechanism(s) and therapeutic implications
Authors: Okajima Kenji 
Published: August 2004

AbstractActivated protein C (APC), a natural anticoagulant, is formed from protein C by the action of the thrombinthrombomodulin (TM) complex on the endothelial cell surface. Endothelial protein C receptor augments the activation of protein C by the thrombin/TM system. APC inactivates the activated form of coagulation factors V and VIII in the presence of protein S. Administration of APC reduced the pulmonary vascular injury and hypotension as well as the coagulation abnormalities by inhibiting production of the tumor necrosis factor-α (TNF-α) in rats given endotoxin (ET). These therapeutic effects of APC could not be attributed to its anticoagulant effects. APC inhibited ET-induced TNF-α production in human monocytes by inhibiting activation of nuclear factor k-B and activator protein-1 in vitro. Administration of the human plasma-derived APC ameliorated coagulation abnormalities without any adverse effects in patients with disseminated intravascular coagulation (DIC). Recombinant APC was reported to reduce the mortality of patients with severe sepsis, and the therapeutic effect was more marked in such patients with overt DIC than those without it.These observations strongly suggest that APC plays important roles in the regulation of inflammation as well as coagulation. Both anti-inflammatory and anticoagulant properties of APC might contribute to the therapeutic usefulness in patients with severe sepsis.
Autoantibodies against oxidized low-density lipoprotein (ox-LDL) and LDL oxidation status
Authors: Brizzi Patrizia , Tonolo Giancarlo , Bertrand Graziano , Carusillo Francesca , Severino Cristiana , Maioli Mario , Malaguarnera Lucia , Musumeci Salvatore 
Published: August 2004

AbstractOxidized low-density lipoproteins (ox-LDLs) and their autoantibodies (OLAB) are involved in the development of atherosclerosis in animal models, but their role in humans is still not clear. For this reason we studied 54 patients with β-thalassemia major (TM), as a model of chronically low circulating LDLs with a high level of oxidation; 44 patients with primary hypercholesterolemia, as model of chronically high circulating LDLs; 24 type 2 diabetic mellitus patients (T2DM) before and after 3 months of atorvastatin treatment (20 mg/day), as a model of acute changes in circulating LDLs; and 41 normolipidemic subjects as a control group. ox-LDLs were measured by the determination of baseline diene concentration in the plasma LDL lipidic fraction after 12 hours fasting and were expressed as the amount of conjugated dienes/liter (BDC/l) or BDC/LDL-cholesterol (LDL-C), which indicate respectively LDL oxidation degree and status. OLABwere determined using an enzyme immunoassay and related to LDL oxidation degree (BDC/l). In TM, BDC/l was lower, while BDC/LDL-C was significantly higher, compared to both hypercholesterolemia and normolipidemic subjects. Patients with hypercholesterolemia had higher BDC/l, but lower BDC/LDL-C and OLAB/BDC-l, than normolipidemic subjects. In T2DM patients at diet, BDC/LDL-C and OLAB/BDC-l were lower than in normolipidemic subjects. After 3 months of atorvastatin treatment, BDC/LDL-C and OLAB/BDC-l ratios increased. When all patients were evaluated together, a significant inverse correlation was evident between OLABand either LDL or BDC/l. Our findings suggest that a relationship between OLABtiter and oxidation indices (BDC/l and BDC/LDL-C) does exist and we may speculate that an increase in OLAB/BDC-l ratio might be protective against the risk of atherosclerosis.
Environmental dichlorodiphenyltrichlorethane or hexachlorobenzene exposure and breast cancer: is there a risk?
Authors: Charlier Corinne , Foidart Jean-Michel , Pitance François , Herman Philippe , Gaspard Ulysse , Meurisse Michel , Plomteux Guy 
Published: August 2004

AbstractThe carcinogenic potential of environmental xenoestrogens (i.e., organochlorines) is a matter of controversy. Their pathogenic role as promoters in breast cancer has been previously suggested. In Europe, despite their prohibition since the ’70s, residues persist in soil and rivers resulting in a widespread contamination of the general population. In this study, we have compared the serum levels of p,p'-1,1-dichloro-2, 2-bis (4-chlorophenyl) ethylene (DDE) and hexachlorobenzene (HCB) in 231 women at the time of breast cancer discovery and in 290 age-matched healthy controls. p,p'-DDE was found in 76.2% of cases and in 71.1% of controls but HCB was present only in 12.6% of cases (29 from 231) and in 8.9% of controls (26 from 290). Even if taking all undetectable results (recorded as “0”) into consideration, mean values were significantly different in cases when compared to controls. The serum level of p,p'-DDE was 3.46±3.48 ppb (0.58±0.58 μg/g lipid) in patients and 1.85±2.09 ppb (0.31±0.35 μg/g lipid) in controls (p<0.0001). The HCB serum level was 0.66±1.25 ppb (0.11±0.21 μg/g lipid) in patients and 0.20±1.02 ppb (0.03±0.17 μg/g lipid) in controls (p<0.0001). When considering p,p'-DDE and HCB as binary variables (1 if higher than the limit of quantification, 0 if lower), the presence of both residues was significantly associated with an increased risk of breast cancer development (OR 2.21, 95% CI 1.41–3.48 for p,p'-DDE and OR 4.99, 95% CI 2.95–8.43 for HCB). No excess was observed among parous women or when familial history of breast cancer was considered. In the cancer group, no differences in serum levels of p,p'-DDE or HCB were found in relation with estrogen-receptor (ER) status, Bloom stage or lymph node metastasis, but the HCB level was moderately correlated with tumor size (p=0.026).
Analytical performance and method comparison study of the total homocysteine fluorescence polarization immunoassay (FPIA) on the AxSYM analyzer
Authors: Lonati Silvia , Novembrino Cristina , Ippolito Silvia , Accinni Roberto , Galli Claudio , Troonen Hugo , Campolo Jonica , Noce Cinzia Della , Lunghi Giovanna , Catena Fabrizia Bamonti 
Published: August 2004

AbstractA fluorescence polarization immunoassay (FPIA) has been commercially released for routine large-scale testing of total homocysteine (tHcy) on the AxSYM analyzer. We evaluated the analytical performance of the AxSYM tHcy FPIA and compared it with the well established high-performance liquid chromatography (HPLC) and IMx tHcy FPIA methods. Homocysteine concentrations were measured by AxSYM and IMx tHcy FPIA and by a rapid isocratic HPLC method with fluorescence detection. Coefficient of variation (CV) of total imprecision for AxSYM tHcy was ≤5%, mean dilution recovery 102%, analytical sensitivity 0.70 μmol/l and linearity was good up to 1:8 dilution. Spearman rank correlations, rho, were 0.83 (p<0.0001) for AxSYM vs. HPLC, 0.97 (p<0.0001) for AxSYM vs. IMx and 0.83 (p <0.0001) for IMx vs. HPLC. Passing and Bablok regression Y-intercepts and slopes were: 2.944/0.937 (AxSYM vs. HPLC), −0.367/1.142 (AxSYM vs. IMx) and 2.632/0.805 (IMx vs. HPLC). Corresponding mean differences (AxSYM-Comparison Assay) recorded over a 5–50 μmol/l measured range were 1.80, −0.73 and 2.53 μmol/l. AxSYM tHcy FPIA's first rate precision, supported by the complete automation of the AxSYM analyzer, makes it fit for routine use and suitable for laboratories requiring homocysteine high-throughput testing capabilities.
Intravenous immunoglobulin (IVIG): modes of action in the clinical management of recurrent pregnancy loss (RPL) and selected autoimmune disorders
Authors: Omwandho Charles O. A. , Gruessner Susanne E. M. , Roberts Timothy K. , Tinneberg Hans Rudolf 
Published: August 2004

AbstractRecurrent pregnancy loss has been associated with autoimmune responses to membrane phospholipids and alloimmune reactions against paternally derived molecules on the trophoblast. The problem is psychologically and economically stressful as it undermines the capacity of some couples to reproduce and participate effectively in the day-to-day economic activities. This article reviews the adoption of intravenous immunoglobulin as a form of therapy for the clinical management of recurrent pregnancy loss and of selected autoimmune disorders. Side effects, contraindications and safety of use are discussed.
Abnormalities in apolipoprotein and lipid levels in an HIV-infected Brazilian population under different treatment profiles: the relevance of apolipoprotein E genotypes and immunological status
Authors: Malavazi Iran , Abrão Emiliana P. , Mikawa Angela Y. , Landgraf Viviane O. , Costa Paulo I. da 
Published: August 2004

AbstractHIV infection is associated with disturbances in lipid metabolism due to a host's response mechanism and the current antiretroviral therapy. The pathological appearance and progression of atherosclerosis is dependent on the presence of injurious agents in the vascular endothelium and variations in different subsets of candidate genes. Therefore, the
Amphetamines and 3,4-methylendioxymetamphetamine (MDMA): evaluation of KIMS (kinetic interaction of microparticles in solution) assay at two cut-off levels
Authors: Marchioro Lucio , Bassetto Flavia , Dall'Olio Giuliano , Tedeschi Luciano , Castagna Franca , Plebani Mario 
Published: August 2004

AbstractTwo screening methods for the assay of amphetamines and their derivatives have been applied to the same analytical instrument for their evaluation. In addition to an assay at a cut-off of 1000 μg/l, a new specific reagent was evaluated for an ultra-sensitive assay of amphetamines and 3,4-methylendioxyme-tamphetamine with a cut-off of 300 μg/l. The assay confirmation was performed using high-performance liquid chromatography and gas chromatography/mass spectrometry techniques. The results were positive for both screening methods, confirming the efficacy of two simultaneous methods with different cut-off levels.