bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution and mRNA Expression of Insulin-Like Growth Factor System in Pulmonary Lymphangioleiomyomatosis
Authors: Valencia Julio C. , Matsui Kazuhiro , Bondy Carolyn , Zhou Jian , Rasmussen Audrey , Cullen Kevin , Yu Zu-Xi , Moss Joel , Ferrans Victor J. 
Published: August 2007

Background Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors. Methods To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients. Results IGF-1, IGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 were observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells. Conclusions These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells.
Susceptibility to Cytomegalovirus Infection May be Dependent on the Cytokine Response to the Virus
Authors: Geist Lois J. , Hinde Sara L. 
Published: August 2007

Background Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in an immunocompromised host. Pulmonary infection with CMV results in an inflammatory response, which includes the local production of cytokines. Cytokine production stimulated by CMV infection serves to activate a series of immunologic responses involved in viral clearance. Previous work has demonstrated that different mouse strains express variable sensitivity to CMV infection. Methods Using mouse strains that express sensitive (BALB/cj) and resistant (C57BL/6) CMV phenotypes, we asked whether the differences in susceptibility to infection were caused by differences in pulmonary cytokine production after intraperitoneal infection with CMV. Results C57 mice demonstrated a higher total bronchoalveolar lavage (BAL) and BAL lymphocyte count at 3 and 7 days after intraperitoneal infection compared with BALB mice. There were no differences in BAL cytokine production; however, we were able to demonstrate differences in CMV DNA load in the lungs of BALB mice compared with that of C57 mice. In addition, there appeared to be increased whole-lung production of the TH2 cytokine IL-10 in the BALB mice versus the C57 mice. Conclusions This observation suggests that the genetic susceptibility to CMV infection may, in part, be regulated by differences in cytokines production within the local environment.
Effect of Simvastatin Alone and in Combination with Cytosine Arabinoside on the Proliferation of Myeloid Leukemia Cell Lines
Authors: Lishner Michael , Bar-Sef Avigdor , Elis Avishay , Fabian Ina 
Published: August 2007

Background Cholesterol biosynthesis is regulated by the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol and its derivatives are required in high concentrations by neoplastic proliferating cells for both DNA synthesis and cell growth. Thus, inhibition of HMG-CoA reductase could effect cell cycle progression and proliferation. Therefore, we examined the effect of an HMG-CoA reductase inhibitor (simvastatin) alone and in combination with cytosine arabinoside (ARA-C) on the proliferation of two AML cell lines. Methods AML blasts derived from two cell lines (HL-60 and AML-2) were incubated with increasing concentrations of either simvastatin alone or simvastatin alone for 24 hours with ARA-C added thereafter. The effect of the drugs on cell proliferation in liquid culture (3 H thymidine uptake) and on clonogenic assay was analyzed. Results We found that the number of proliferating AML blasts (suspension cultures) and colony formations (agar cultures) of both cell lines declined significantly after incubation with simvastatin. Preincubation of both cell lines with simvastatin by the addition of increasing concentrations of ARA-C produced a degree of growth inhibition that was significantly greater than that of the individual compounds. This antigrowth interaction was additive rather than synergistic. Conclusions We conclude that simvastatin has a major antiproliferative effect on AML blasts in vitro. Also, the combination of simvastatin and ARA-C significantly enhanced the antiproliferative effect of each drug. These findings may open new avenues in both the laboratory and clinical research of the treatment of leukemia.
Erythropoietin Withdrawal Alters Interactions between Young Red Blood Cells, Splenic Endothelial Cells, and Macrophages: An in Vitro Model of Neocytolysis
Authors: Trial JoAnn , Rice Lawrence , Alfrey Clarence P. 
Published: August 2007

Background We have described the rapid destruction of young red blood cells (neocytolysis) in astronauts adapting to microgravity, in polycythemic high altitude dwellers who descend to sea level, and in patients with kidney disorders. This destruction results from a decrease in erythropoietin (EPO) production. We hypothesized that such EPO withdrawal could trigger physiological changes in cells other than red cell precursors and possibly lead to the uptake and destruction of young red cells by altering endothelial cell-macrophage interactions, most likely occurring in the spleen. Methods We identified EPO receptors on human splenic endothelial cells (HSEC) and investigated the responses of these cells to EPO withdrawal. Results A monolayer of HSEC, unlike human endothelial cells from aorta, glomerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When HSEC were cultured with monocyte-derived macrophages (but not when either cell type was cultured alone), EPO withdrawal induced an increased ingestion of young red cells by macrophages when compared with the constant presence or absence of EPO. Conclusions HSEC may represent a unique cell type that is able to respond to EPO withdrawal by increasing permeability and interacting with phagocytic macrophages, which leads to neocytolysis.
Association of Traditional Risk Factors with Coronary Calcification in Persons with a Family History of Premature Coronary Heart Disease: The Study of the Inherited Risk of Coronary Atherosclerosis
Authors: Valdes Ana M. , Wolfe Megan L. , Tate Helen C. , Gefter Warren , Rut Andrew , Rader Daniel J. 
Published: August 2007

Background Genetic factors strongly influence the risk of coronary heart disease (CHD), but their contribution to variation in coronary atherosclerosis beyond that measured by traditional CHD risk factors is uncertain. Methods We recruited healthy subjects with family histories of premature CHD. We assessed traditional risk factors and performed electron beam tomography (EBT) to quantitate coronary artery calcification (CAC), a marker of coronary atherosclerosis. Persons with significant risk factors that included diabetes, total cholesterol >300 mg/dL, active cigarette smoking, and poorly controlled hypertension were excluded from the study. In this paper, we report on the relationship between traditional risk factors and CAC in this cohort. Results The incidence of coronary calcification was significantly higher in this cohort than in the population-based Rochester Heart Study. In our cohort, most traditional risk factors were significantly associated with CAC on univariate analysis. On the other hand, in stepwise logistical regression, age and triglycerides were the only predictors of variation in CAC in men and accounted for only 30% of the variation; in women, age, body mass index (BMI), and triglycerides were the only traditional risk factors significantly associated with CAC variation and accounted for 22.2% of CAC variance. Conclusions In a cohort of subjects specifically selected for the characteristic of a family history of premature CHD, traditional risk factors accounted for less than one-third of the variation in CAC, and the most important predictors of CAC after age were plasma triglycerides. This supports the opinion that other inherited risk factors have important effects on the variation in coronary atherosclerosis and that the strategy of using EBT to phenotype clinically asymptomatic subjects with regard to coronary atherosclerosis may be a useful tool for identification of genes that are associated with CHD.
Multilink Stent Promotes Less Platelet and Leukocyte Adhesion than a Traditional Stainless Steel Stent: An in Vitro Experimental Study
Authors: Amoroso Giovanni , Van Boven Ad J. , Volkers Corine , Crijns Harry J.G.M. , Van Oeveren Wim 
Published: August 2007

Background Platelet and leukocyte deposition onto metallic struts can be a crucial factor in the outcome of a coronary stenting procedure. By means of an in vitro, closed-loop circulation model, we aimed to assess blood-stent interaction patterns for a new stainless steel stent (MultiLink, Guidant Nederland BV, Nieuwegein, the Netherlands). Methods The effect of MultiLink (n=20) on blood cells and blood activation was studied by biochemical assays. Platelet and leukocyte adhesion to MultiLink were studied by immunofluorocytometric assays (anti-GpIIIa [CD 61] and anti-CD11b labeled antibodies, respectively), and by scanning electron microscopy. MultiLink was compared with empty circuits (n=20) and to the Palmaz Schatz stent (n=20). Experiments were performed both in the presence and in the absence of an antiplatelet agent (15 μg/mL of indomethacin). Results No significant effect on blood cells and blood activation was demonstrated for MultiLink. Antiplatelet treatment significantly reduced platelet adhesion to MultiLink (from 3.78±1.28 to 2.23±0.57x106 count per second [cps]/stent) but not to the Palmaz Schatz stent (from 4.11±0.31 to 5.02±1.29x106 cps/stent)( P=0.011). Leukocyte adhesion to MultiLink was significantly less than adhesion to the Palmaz Schatz stent (7.95±1.59 vs. 9.16±1.36x106 cps/stent, respectively; P=0.016), regardless of the presence of antiplatelet treatment. Conclusions When compared with a traditional stainless steel stent, MultiLink seems to have features of improved hemocompatibility, and single antiplatelet treatment is proposed as the treatment of choice to prevent platelet deposition.
B-Cell Kinase Lyn Deficiency in Patients with Systemic Lupus Erythematosus
Authors: Liossis Stamatis-Nick C. , Solomou Elena E. , Dimopoulos Meletios-Athanasios , Panayiotidis Panayiotis , Mavrikakis Myron M. , Sfikakis Petros P. 
Published: August 2007

Background To better understand the molecular background of B-cell overactivity characterizing systemic lupus erythematosus (SLE), we examined the expression of the CD22 co-receptor and of kinase Lyn, which are involved in signaling inhibitory pathways, in B cells from patients with SLE. Methods Two-color flow cytometry was used to study the expression of surface antigens on freshly isolated peripheral B cells from patients with SLE, disease-control patients, and healthy volunteers. Intracellular kinases Lyn and Syk were analyzed using Western immunoblots, and differences at the messenger RNA (mRNA) level were evaluated using semiquantitative polymerase chain reaction (PCR). Results Expression of B-cell surface CD22 was intact in patients with SLE, but expression of the B-cell kinase Lyn was significantly decreased in resting, as well as in anti-sIgM-stimulated B-cell-enriched cell lysates obtained from 66% of patients with SLE. Lyn deficiency was disease-specific and unrelated to disease activity. Expression of B-cell kinase Syk was similar in all study groups. Semiquantitative PCR revealed that Lyn mRNA was significantly decreased in lupus patients with decreased Lyn protein expression, suggesting that Lyn deficiency may be caused at least in part by defects at the transcription level. Conclusions Decreased expression of Lyn in some patients with SLE represents a B-cell defect that may enhance our understanding of SLE molecular pathogenesis by providing rational therapeutic targets.
New Technique for Gene Transfection Using Laser Irradiation
Authors: Shirahata Yasuhiro , Ohkohchi Nobuhiro , Itagak Hideo , Satomi Susumu 
Published: August 2007

Background We have developed a gene transfection system using laser beams. The principle of this procedure is that a small hole is made in a cell membrane by pulse laser irradiation, and a gene contained in a medium is transferred into the cytoplasm through the hole. This hole disappears immediately with the application of laser irradiation of the appropriate power. Methods A pulse-wave Nd:YAG laser with a wavelength of 355 nm was used to make a hole in a cell membrane. To trap a cell, a continuous-wave Nd:YAG laser with a wavelength of 1015 nm was used. Plasmids that encode the enhanced green fluorescent protein (EGFP) gene were contained in a medium and transferred to HuH-7 and NIH/3T3 cells with pulse laser irradiation. We evaluated transfection efficiency on the basis of the number of cells that expressed EGFP. Stimulatory protein 2 cells in suspension were fixed using a trapping laser and the neomycin-resistance gene was transfected by pulse laser irradiation. We examined cell proliferation in the selection medium. Results Cells that expressed EGFP were recognized in the group that was irradiated by pulse laser. No cells expressed EGFP without irradiation. Transfection efficiency was ≈10% at a plasmid concentration of 10.0 μg/mL. At concentrations greater than 20 μg/mL, the transfection rate reached a plateau. We also successfully transfected neomycin-resistance genes to cells floating in suspension after fixation that was achieved with trapping laser irradiation. Conclusions This method enables us to transfect targeted cells, ie, cells in suspension as well as attached cells, with a simple technique that does not involve harmful vectors. The present method is very useful for gene transfection in cellular biotechnology.
Increased Sensitivity to Glucocorticoids in Peripheral Blood Mononuclear Cells of Chronic Fatigue Syndrome Patients, without Evidence for Altered Density or Affinity of Glucocorticoid Receptors
Authors: Visser Jeroen , Lentjes Eef , Haspels Inge , Graffelman Willy , Blauw Bep , de Kloet Ronald , Nagelkerken Lex 
Published: August 2007

Background In this study we tested the hypothesis that the increased sensitivity to glucocorticoids in chronic fatigue syndrome (CFS)-patients can be attributed to an altered functioning of their glucocorticoid receptors (GR). Methods For this purpose, affinity and distribution of the GR were studied in purified, peripheral blood mononuclear cells (PBMC) of 10 CFS patients and 14 controls along with the responsiveness of these cells to glucocorticoids in vitro. Results Affinity (Kd) and number of GR was not different in PBMC of CFS patients when compared with the controls (Kd, 12.9±8.9 nmol vs 18.8±16.2 nmol and GR number, 4839±2824/cell vs 4906±1646/cell). Moreover, RT-PCR revealed no differences in GR messenger RNA expression. Nevertheless, PBMC from CFS patients showed an increased sensitivity to glucocorticoids in vitro. In CFS patients 0.01 μmol dexamethasone suppressed PBMC proliferation by 37%, whereas the controls were only suppressed by 17% ( P <0.01). Addition of phorbol 12-myristate 13-acetate to the cultures rendered the cells resistant to dexamethasone with regard to proliferation and IL-10 and IFN-γ production, but not to IL-2 and TNF-α production in both patients and controls. No difference between patients and controls was observed in this respect. Conclusions In conclusion, PBMC of CFS patients display an increased sensitivity to glucocorticoids, which cannot be explained by number or affinity of the GR but should rather be attributed to molecular processes beyond the actual binding of the ligand to the GR.
Productivity of Medical Research in Switzerland
Authors: Bovier Patrick A. , Guillain Hervé , Perneger Thomas V. 
Published: August 2007

Background Little evidence exists about what contributes to successful medical research, an increasingly important issue in an era of limited research budgets. This study examined predictors of productivity of Swiss medical research. Methods Principal investigators of clinical research projects funded by the Swiss National Science Foundation between 1990 and 1994 were surveyed by mail. They provided information about the research question, whether changes were made to the protocol and why, their assessment of the importance of results for science and for public health, and additional funding of the project. The amount of the grant and the project priority score were obtained from the Foundation. Indicators of scientific productivity were the number of peer-reviewed articles and the summed impact factor per grant. Results The size of the grant predicted scientific output (number of articles and summed impact factor), but the marginal return decreased with the total sum awarded. The award of a continuation grant by the same agency and additional funding from other sources were also positively linked with productivity. In addition, the initial priority rating of the project by the funding agency's scientific committee and the assessment of scientific importance of the results by the principal investigator were also independently associated with productivity. Finally, modifications of the initial research plan in response to new scientific opportunities were linked with greater productivity, whereas modifications induced by technical or other difficulties were associated with lower productivity. Conclusions Productivity in medical research, measured by peer-reviewed articles produced, requires adequate resources and ability to respond to new scientific challenges, and it can be anticipated by peer-review.
Insulin Receptor Antibodies Inhibit Insulin Uptake by the Liver: In Vivo 123I-Insulin Scintigraphic Scanning and in Vitro Characterization in Autoimmune Hypoglycemia
Authors: Dozio N. , Sarugeri E. , Scavini M. , Beretta A. , Belloni C. , Dosio F. , Savi A. , Fazio F. , Sodoyez-Goffaux F. , Pozza G. 
Published: August 2007

Background Insulin receptor antibodies can induce severe hypoglycemia or insulin resistance in rare autoimmune syndromes. In vitro properties of these antibodies occasionally explain the clinical features of the syndrome, but direct evidence of their in vivo activity is poor. We studied a 58-year-old male with rheumatoid arthritis who presented with hypoglycemic coma. Methods and Results Antibodies were detected by inhibition of 125 I-insulin binding to human insulin receptor-3T3 cells by the patient's serum. By immunofluorescence, they were immunoglobulin G of all four subclasses, immunoprecipitated insulin receptors from biotin-labeled cells, and triggered phosphorylation of the beta subunit of the insulin receptor. Insulin binding on the patient's red blood cells was markedly reduced. A biodistribution study after intravenous 123 I-Tyr A14 insulin showed a marked inhibition of tracer uptake by the liver, reaching 10% of the injected dose (controls, mean±SD, 21.1±1.7%; n=10). Time activity curves generated on the liver and on the heart were parallel, with a T1/2 of 11.5 minutes for both, suggesting that no specific uptake occurred in the liver, where tracer activity represented only the blood pool. Clearance of insulin from the blood was indeed slower than in controls and mainly occurred through the kidneys. Analysis of plasma 123 I-insulin immunoreactivity and trichloroacetic acid precipitate showed that insulin degradation did not occur as in normal controls. Conclusions In this patient with hypoglycemic syndrome, insulin receptor antibodies with in vitro insulin-like activity are capable of blocking in vivo the access of insulin to the liver receptor compartment, as directly demonstrated by the markedly altered biodistribution of intravenously injected 123 I-insulin.
Acute Effects of Nitric Oxide Synthase Inhibition on Systemic, Hepatic, and Renal Hemodynamics in Patients with Cirrhosis and Ascites
Authors: Spahr Laurent , Martin Pierre-Yves , Giostra Emile , Niederberger Michel , Lang Ursula , Capponi Allessandro , Hadengue Antoine 
Published: August 2007

Background Nitric oxide synthase (NOS) inhibition has been demonstrated to correct systemic vasodilation and renal hypoperfusion in studies of patients with cirrhosis. In patients with decompensated cirrhosis, NOS blockade increases arterial pressure, but the acute effects on hepatic and renal hemodynamics are not known. Methods We examined the acute systemic, hepatic, and renal hemodynamic effects of NG-monomethyl-l-arginine (l-NMMA) in 10 patients with decompensated cirrhosis. After baseline measurements, 3 mg/kg l-NMMA was administered as an IV bolus. At 20 minutes, if mean arterial pressure did not increase by at least 10 mm Hg above the baseline value, a second injection of 6 mg/kg was administered. Results In 5 of 10 patients, the second injection of l-NMMA 6mg/kg was necessary to achieve at least a 10 mm Hg increase in mean arterial pressure. Acute NOS inhibition increased systemic vascular resistance and decreased cardiac output, without causing changes in the hepatic venous pressure gradient. Hepatic blood flow decreased, but the indocyanine green intrinsic clearance and extraction remained unchanged. Plasma renin activity (from 9.5±2.9 to 6.7±1.6 ng/ml/h) and urinary prostaglandin E2 (from 299±40 to 112±36 pg/ml) significantly decreased. No significant changes in glomerular filtration rate, renal plasma flow, and natriuresis occurred, however. Conclusions Acute l-NMMA infusion in patients with decompensated cirrhosis reduced hepatic blood flow and decreased plasma renin activity and urinary prostaglandin E2, without causing significant changes in renal hemodynamics.
Thioredoxin and Protein Nitrotyrosine in Bone Marrow Supernatant from Patients with Human Immunodeficiency Virus Infection
Authors: van Laer An , Dallalio Gail , McKenzie Stacey W. , Means Robert T. 
Published: August 2007

Background Balance and imbalance between oxidant stress and antioxidants contributes to the manifestations of human immunodeficiency virus (HIV) infection. Previously, we demonstrated a characteristic cytokine pattern in marrow supernatant from HIV patients who underwent diagnostic examinations. Methods In this report, we have determined the protein nitrotyrosine (pNT) concentration (an indicator of nitric oxide-superoxide interaction) as well as the concentration of the redox enzyme thioredoxin (Trx) in marrow supernatant from HIV patients, healthy controls, and other patients, and in serum from comparable subjects. Results pNT concentrations were similar in serum and marrow supernatant and did not differ between subject subsets. Trx concentrations in both marrow supernatant and serum were higher for HIV patients than for other subjects; serum Trx concentrations were significantly higher than marrow Trx concentrations for the non-HIV patients and controls. The ratios of pNT/Trx concentrations in serum were similar in all subsets tested. In marrow aspirate, however, these ratios differed widely and significantly, with the highest values observed in non-HIV patients and the lowest in HIV patients. Only for HIV patients were serum and marrow supernatant pNT/Trx ratios similar. In HIV patients, marrow Trx concentrations correlated with CD4 count, CD4/CD8 ratio, and marrow colony-forming unit E (CFU-E) concentration; marrow pNT concentration correlated with the concentration of tumor necrosis factor in marrow supernatant, and with platelet count. No correlations were observed in other subject subsets. Conclusions These findings suggest that there is a degree of local regulation of the redox state of the marrow microenvironment that varies with the patients’ clinical statuses, and which is associated with effects on hematopoiesis.