bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13
Authors: Bonnefoy Arnaud , Daenens Kim , Feys Hendrik B. , De Vos Rita , Vandervoort Petra , Vermylen Jos , Lawler Jack , Hoylaerts Marc F. 
Published: October 2005

AbstractThe function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1-/- mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1-/- platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1-/- vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1-/- vessels. Injection of human TSP-1 or thrombotic thrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1-/- mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1-/- venules (1027 ± 377 seconds) and arterioles (858 ± 289 seconds) than in WT vessels (559 ± 241 seconds, P < .001; 443 ± 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and anti-ADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively.
Dendritic cells regulate T-cell deattachment through the integrin-interacting protein CYTIP
Authors: Hofer Susanne , Pfeil Karina , Niederegger Harald , Ebner Susanne , Nguyen Van Anh , Kremmer Elisabeth , Auffinger Margit , Neyer Susanne , Fürhapter Christina , Heufler Christine 
Published: October 2005

AbstractWhen T cells are primed by dendritic cells (DCs) to initiate antigen-specific immune responses screening for matching antigen receptor-MHC/peptide pairs takes place in DC-T-cell conjugates. For an immune response DC-T-cell conjugates formed during priming events need to dissolve. Although detailed knowledge on molecules involved in the conjugate formation is available, dissolving of them has not been considered to be an active process. Here, we identify CYTIP (cytohesin-interacting protein) to mediate DC-T-cell deattachment. CYTIP, which is induced during maturation of DCs, shortly accumulates to the contact zones with T cells within the first hour of coculture. Specific silencing of CYTIP results in stronger adhesion of DCs to T cells and to fibronectin. When a need for deattachment is created in a T-cell priming assay by only partially loading DCs with antigen, CYTIP silencing causes reduced priming capacity. Thus, CYTIP allows DCs to actively control DC-T-cell interactions.
cAMP-induced PKCζ activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors
Authors: Goichberg Polina , Kalinkovich Alexander , Borodovsky Nataliya , Tesio Melania , Petit Isabelle , Nagler Arnon , Hardan Izhar , Lapidot Tsvee 
Published: October 2005

AbstractChemokines are key regulators of hematopoiesis and host defense. We report here that functional expression of the chemokine receptor CXCR4 on human immature CD34+ hematopoietic progenitors was increased as a result of sustained elevation in cellular cAMP by dbcAMP and prostaglandin E2. This effect of cAMP was specifically mediated by PKCζ activity. CXCR4 expression and PKCζ activation by cAMP were decreased after the inhibition of cAMP effector-Rap1 by Spa1 overexpression. Interference with the activation of Rac1, a downstream target of Rap1, prevented the cAMP-induced increase in PKCζ activity and CXCR4 levels. Functional manifestation of the effects of cAMP-elevating agents revealed an increased ability of human CD34+ cells to transmigrate the bone marrow (BM) endothelial layer and adhere to BM stroma in vitro, and it augmented the homing potential to the BM and spleens of immunodeficient mice in a Rac1- and a PKCζ-dependent manner. cAMP- and TNFα-stimulated pathways converged in PKCζ-activated CXCR4 expression and MMP-2/MMP-9 secretion. cAMP treatment had a beneficial effect on CD34+ cell survival in a PKCζ-mediated fashion. Taken together, our data reveal major roles for cAMP-induced PKCζ activation in signaling governing the motility and development of CD34+ cells.
Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury
Authors: Arimura Akira , Li Min , Batuman Vecihi 
Published: October 2005

AbstractThe most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as “myeloma kidney” that often progresses to end-stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that pituitary adenylate cyclase-activating polypeptide with 38 residues (PACAP38) dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFκB via both PAC1 and VPAC1 receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma.
Length of patient-physician relationship and patients' satisfaction and preventive service use in the rural south: a cross-sectional telephone study
Authors: Donahue Katrina E , Ashkin Evan , Pathman Donald E 
Published: October 2005

Abstract

Background
Physicians and patients highly value continuity in health care. Continuity can be measured in several ways but few studies have examined the specific association between the duration of the patient-doctor relationship and patient outcomes. This study (1) examines characteristics of rural adults who have had longer relationships with their physicians and (2) assesses if the length of relationship is associated with patients' satisfaction and likelihood of receiving recommended preventive services.

Methods
Cross-sectional telephone survey of health care access indicators of adults in selected non-metropolitan counties of eight U.S. predominantly southern states. Analyses were restricted to adults who see a particular physician for their care and weighted for demographics and county sampling probabilities.

Results
Of 3176 eligible respondents, 10.8% saw the same physician for the past 12 months, 11.8% for the previous 13–24 months, 20.7% for the past 25–60 months and 56.7% for more than 60 months. Compared to persons with one year or less continuity with the same physician, respondents with over five years continuity more often were Caucasian, insured, a high school graduate, and more often reported good to excellent health and an income above $25,000. Compared to those with more than five years of continuity, participants with either less than one year or one to two years of continuity with the same physician were more often not satisfied with their overall health care (OR 2.34; OR 1.78), participants with less than one year continuity were more often not satisfied with the concern shown them by their physician (O.R. 1.90) and having their health questions answered, and those with one to two years continuity were more often not satisfied with the quality of their care (OR 2.37). No significant associations were found between physician continuity and use rates of any of the queried preventive services.

Conclusion
Over half of this rural population has seen the same physician for more than five years. Longer continuity of care was associated with greater patient satisfaction and confidence in one's physician, but not with a greater likelihood of receiving recommended preventive services.
Alteration of protein expression pattern of vascular endothelial growth factor (VEGF) from soluble to cell-associated isoform during tumourigenesis
Authors: Cressey Ratchada , Wattananupong Onusa , Lertprasertsuke Nirush , Vinitketkumnuen Usanee 
Published: October 2005

Abstract

Background
Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells, and its expression has been correlated with increased tumour angiogenesis. Although numerous publications dealing with the measurement of circulating VEGF for diagnostic and therapeutic monitoring have been published, the relationship between the production of tissue VEGF and its concentration in blood is still unclear. The aims of this study were to determine: 1) The expression pattern of VEGF isoforms at the protein level in colorectal and lung adenocarcinoma in comparison to the pattern in corresponding adjacent normal tissues 2) The relationship between the expression pattern of VEGF and total level of circulating VEGF in the blood to clarify whether the results of measuring circulating VEGF can be used to predict VEGF expression in tumour tissues.

Methods
Ninety-four tissue samples were obtained from patients, 76 colorectal tumour tissues and 18 lung tumour tissues. VEGF protein expression pattern and total circulating VEGF were examined using western blot and capture ELISA, respectively.

Results
Three major protein bands were predominately detected in tumour samples with an apparent molecular mass under reducing conditions of 18, 23 and 26 kDa. The 18 kDa VEGF protein was expressed equally in both normal and colorectal tumour tissues and predominately expressed in normal tissues of lung, whereas the 23 and 26 kDa protein was only detected at higher levels in tumour tissues. The 18, 23 and 26 kDa proteins are believed to represent the VEGF121, the VEGF165 and the VEGF189, respectively. There was a significant correlation of the expression of VEGF165 with a smaller tumour size maximum diameter <5 cm (p < 0.05), and there was a significant correlation of VEGF189 with advanced clinical stage of colorectal tumours. The measurement of total circulating VEGF in serum revealed that cancer patients significantly (p < 0.001) possessed a higher level of circulating VEGF (1081 ± 652 pg/ml in colorectal and 1,251 ± 568 pg/ml in lung) than a healthy volunteer group (543 ± 344 pg/ml). No correlation between the level of circulating VEGF and the pathologic features of tumours was observed.

Conclusion
Our findings indicate that the expression patterns of VEGF isoforms are altered during tumourigenesis as certain isoform overexpression in tumour tissues correlated with tumour progression indicating their important role in tumour development. However, measurement of VEGF in the circulation as a prognostic marker needs to be carefully evaluated as the cell-associated isoform (VEGF189), but not the soluble isoform (VEGF121 and VEGF165) appears to play important role in tumour progression.
Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy
Authors: Trieschmann Lothar , Santos Alexander Navarrete , Kaschig Katja , Torkler Sandra , Maas Elke , Schätzl Hermann , Böhm Gerald 
Published: October 2005

Abstract

Background
The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans or bovine spongiform encephalopathy (BSE) in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc) in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods.

Results
We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10-8 nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle.

Conclusion
We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.
Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation
Authors: Sawai Hirozumi , Okada Yuji , Funahashi Hitoshi , Matsuo Yoichi , Takahashi Hiroki , Takeyama Hiromitsu , Manabe Tadao 
Published: October 2005

Abstract

Background
Interaction with integrin and focal adhesion kinase (FAK) regulates the cancer cell adhesion and invasion into extracellular matrix (ECM). In addition, phosphorylation of FAK correlates with the increase of cell motility and invasion. Adhesion and spreading of cancer cells on a variety of ECM proteins, including collagen type IV (Coll IV), leads to an increase in tyrosine phosphorylation and activation of FAK. In this study, we investigated the mechanism of activation of FAK and its downstream extracellular signal-regulated kinase (ERK)-1/2 signaling following stimulation by interleukin (IL)-1α and adhesion to ECM with subsequent enhancement of pancreatic cancer cell adhesion and invasion.

Results
In immunoblotting analysis, all three pancreatic cancer cell lines (AsPC-1, BxPC-3, and Capan-2) expressed the protein of FAK and β1 integrin. Enhancement of FAK protein association with β1 integrin when cells were plated on Coll IV was more increased by stimulation with IL-1α. Preincubation with anti-β1 integrin antibody and FAK siRNA transfection inhibited the association of FAK with β1 integrin of pancreatic cancer cells. FAK phosphorylation was observed by adhesion to Coll IV, furthermore, stronger FAK phosphorylation was observed by stimulation with IL-1α of pancreatic cancer cells adhered to Coll IV in time-dependent manner. Genistein, a tyrosine kinase inhibitor, markedly inhibited the FAK phosphorylation. IL-1α stimulation and Coll IV adhesion enhanced the activation of Ras, as evidenced by the increased Ras-GTP levels in pancreatic cancer cells. Activation of Ras correlated with the phosphorylation of ERK. While not statistical affecting the apoptosis of pancreatic cancer cells, IL-1α-induced adhesion and invasion on Coll IV were inhibited with FAK gene silencing by siRNA, β1 integrin blocking, and inhibition of FAK phosphorylation. PD98059, a MEK inhibitor, also inhibited IL-1α-induced enhancement of adhesion and invasion in pancreatic cancer cells.

Conclusion
Our results demonstrated that activation of FAK is involved with the aggressive capability in pancreatic cancer through Ras/ERK signaling pathway. Based on our results, we suggest that the modification of IL-1, FAK, and integrins functions might be a novel therapeutic approach to aggressive spread of pancreatic cancer.
The influence of walking performed immediately before meals with moderate fat content on postprandial lipemia
Authors: Pfeiffer Martina , Ludwig Tanja , Wenk Caspar , Colombani Paolo C 
Published: October 2005

Abstract

Background
Postprandial lipemia is an independent risk factor for coronary heart disease. Single bouts of moderate exercise may lower this risk, but the minimum duration of moderate intensity exercise that still lowers postprandial lipemia is not known. We, therefore, performed a dose-response study with a normal, daily life setting, to identify the minimum duration of moderate intensity walking that lowers postprandial lipemia in sedentary, healthy young men.

Methods
Sixteen men performed three activity trials (30, 60, or 90 min of treadmill walking at 50% of their individual VO2max) and a control trial with no physical activity in a repeated measures crossover design. The subjects walked immediately before ingestion of the first of two mixed meals, which were served 3 h apart. The meals had a moderate fat content (0.5 g per kg body mass and 33% of total energy per meal) and a macronutrient composition corresponding to current recommendations. Each meal provided one third of the subject's estimated daily energy requirement. Venous blood samples were taken in the fasted state, and then hourly for 6 h after the first meal to assess the postprandial phase. Postprandial lipemia (the incremental area under the curve (dAUC) of triacylglycerol) was compared with a mixed model analysis and Tukey's adjustment.

Results
Postprandial lipemia (dAUC of triacylglycerol) was, compared to the control trial, +2% (P = 1.00), -14% (P = 0.24), and -15% (P = 0.23) in the 30, 60, and 90 min walking trials, respectively.

Conclusion
Moderate intensity walking of 60 and 90 min duration slightly, but insignificantly, reduced postprandial lipemia after two mixed meals with moderate fat content in sedentary, healthy young men, compared to inactivity. Therefore, it should be reconsidered if the acute exercise-induced reduction in postprandial lipemia usually observed in studies using high fat meals is of importance in a real, daily life setting.
School lunch and snacking patterns among high school students: Associations with school food environment and policies
Authors: Neumark-Sztainer Dianne , French Simone A , Hannan Peter J , Story Mary , Fulkerson Jayne A 
Published: October 2005

Abstract

Objectives
This study examined associations between high school students' lunch patterns and vending machine purchases and the school food environment and policies.

Methods
A randomly selected sample of 1088 high school students from 20 schools completed surveys about their lunch practices and vending machine purchases. School food policies were assessed by principal and food director surveys. The number of vending machines and their hours of operation were assessed by trained research staff.

Results
Students at schools with open campus policies during lunchtime were significantly more likely to eat lunch at a fast food restaurant than students at schools with closed campus policies (0.7 days/week vs. 0.2 days/week, p < .001). Student snack food purchases at school were significantly associated with the number of snack machines at schools (p < .001) and policies about the types of food that can be sold. In schools with policies, students reported making snack food purchases an average of 0.5 ± 1.1 days/week as compared to an average of 0.9 ± 1.3 days/week in schools without policies (p < .001). In schools in which soft drink machines were turned off during lunch time, students purchased soft drinks from vending machines 1.4 ± 1.6 days/week as compared to 1.9 ± 1.8 days/week in schools in which soft drink machines were turned on during lunch (p = .040).

Conclusion
School food policies that decrease access to foods high in fats and sugars are associated with less frequent purchase of these items in school among high school students. Schools should examine their food-related policies and decrease access to foods that are low in nutrients and high in fats and sugars.
Hybrid dynamic/static method for large-scale simulation of metabolism
Authors: Yugi Katsuyuki , Nakayama Yoichi , Kinoshita Ayako , Tomita Masaru 
Published: October 2005

Abstract

Background
Many computer studies have employed either dynamic simulation or metabolic flux analysis (MFA) to predict the behaviour of biochemical pathways. Dynamic simulation determines the time evolution of pathway properties in response to environmental changes, whereas MFA provides only a snapshot of pathway properties within a particular set of environmental conditions. However, owing to the large amount of kinetic data required for dynamic simulation, MFA, which requires less information, has been used to manipulate large-scale pathways to determine metabolic outcomes.

Results
Here we describe a simulation method based on cooperation between kinetics-based dynamic models and MFA-based static models. This hybrid method enables quasi-dynamic simulations of large-scale metabolic pathways, while drastically reducing the number of kinetics assays needed for dynamic simulations. The dynamic behaviour of metabolic pathways predicted by our method is almost identical to that determined by dynamic kinetic simulation.

Conclusion
The discrepancies between the dynamic and the hybrid models were sufficiently small to prove that an MFA-based static module is capable of performing dynamic simulations as accurately as kinetic models. Our hybrid method reduces the number of biochemical experiments required for dynamic models of large-scale metabolic pathways by replacing suitable enzyme reactions with a static module.
Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium
Authors: Möller Winfried , Brown David M , Kreyling Wolfgang G , Stone Vicki 
Published: October 2005

AbstractBackgroundParticulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter). Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP) can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis.MethodsIn this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively), such as elemental carbon (EC90), commercial carbon (Printex 90), diesel particulate matter (DEP) and urban dust (UD), were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320μg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively.ResultsImpaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100μg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA) suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.