bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Belief: Incremental Prediction of Obsessive-Compulsive Disorder by Looming Vulnerability Illusions
Authors: Riskind John H. , Rector Neil A.
Published: August 2007

Cognitive models argue that obsessions and compulsions arise from distorted beliefs and exaggerated interpretations of intrusive thoughts. While these models have led to important advances, recent research has suggested the need to go beyond the factors the models identify. One new factor to consider may involve looming vulnerability, the production of dynamic mental scenarios of danger outcomes (e.g., contamination, harming, losing wanted possessions) as rushing through time and space and escalating in odds of harm for the self. Looming vulnerability is a different form of cognition that differs from belief factors because it concerns the process of anticipating noxious events as rapidly rising in risk rather than static beliefs about the final end states (e.g., responsibility, perfection). The present study tested looming vulnerability by examining a small cohort of 37 patients with obsessive-compulsive disorder (OCD). Results provide strong preliminary evidence that looming vulnerability in OCD-related themes (e.g., contamination, hoarding, and pure obsessional) contributes significant and substantial variance to the prediction of obsessive compulsive symptom severity on the Yale-Brown Obsessive-Compulsive Scale beyond the effects of beliefs and interpretations. Thus, looming vulnerability may represent a different form of cognitive vulnerability for the development and persistence of clinical obsessions that warrants further investigation.
Self-Ambivalence and Attachment to Possessions
Authors: Frost Randy O. , Kyrios Michael , McCarthy Katherine D. , Matthews Yanique
Published: August 2007

Doron and Kyrios (2005) have suggested that self-related constructs may be vulnerability factors for the development of obsessive-compulsive disorder (OCD) and associated cognitions, possibly including compulsive buying, hoarding, and materialism. The present study examined the relationship between self-related constructs (self-ambivalence and attachment uncertainty), compulsive acquisition, hoarding, and materialism. As predicted, self-ambivalence and uncertainty were correlated with materialism, compulsive hoarding, and compulsive buying, while compulsive acquisition of free things was correlated with uncertainty. Furthermore, self-ambivalence accounted for significant variance in all three possession-related variables even after controlling for depression and indecisiveness. Uncertainty accounted for significant variance in the compulsive acquisition of free things. Materialism exhibited high to moderate correlations with compulsive buying but low to moderate correlations with compulsive hoarding and no association with free acquisition. Lack of family warmth failed to correlate with acquisition variables but did correlate with depression. Overall, the findings supported the contribution of self-ambivalence and attachment patterns but not early family environment to the understanding of compulsive acquisition, particularly hoarding and buying problems.
Brassica juncea Canola in the Northern Great Plains: Responses to Diverse Environments and Nitrogen Fertilization
Authors: Gan Y. , Malhi S. S. , Brandt S. , Katepa‐Mupondwa F. , Kutcher H. R.
Published: August 2007

Brassica juncea var. juncea canola is a new oilseed species that is developed from B juncea (L.) Czern. mustard with its oil and meal quality equivalent to conventional canola species. Understanding of the phenological characteristics and yield responses to diverse environments will allow the crop to be better adapted to target production areas. This study determined the responses of the juncea canola to various soil‐climatic conditions and was compared with B napus L. canola, B rapa L. canola, juncea mustard, and Sinapis alba L. mustard. The five oilseed species/cultivars were grown under various N fertilizer rates (0, 25, 50, 100, 150, 200, and 250 kg N ha−1), at four Saskatchewan locations from 2003 to 2005. On average, flowering began 40 d after seeding (DAS) for alba mustard and rapa canola (earliest), 49 DAS for napus canola (latest), and 44 DAS for juncea canola (intermediate). Flowering duration was longest for juncea canola (30 d) and shortest for napus canola (22 d). The napus canola and juncea mustard produced higher (1684 kg ha−1) seed yields than the three other oilseeds (1303 kg ha−1 on average). For all oilseed species, the seed yield was highly responsive to N fertilizer rates from zero to about 100 kg N ha−1, and thereafter, the rate of yield responses declined. The amount of N fertilizer required to achieve the maximum seed yield was 106 kg N ha−1 for rapa canola, 135 kg N ha−1 for alba mustard and napus canola, and 162 kg N ha−1 for the two juncea spp. Overall, juncea canola had lower seed yield than more popular hybrid napus canola, and the yield stability of juncea canola was lowest among the five oilseed species when examined across diverse environments. Earlier flowering, longer flowering duration, and greater tolerance to drought stress exhibited by juncea canola make the crop best adapted to the drier areas of the northern Great Plains. The improvement of seed yield and yield stability is the key to potentially adapt this new oilseed species to a wider range of environmental conditions.
Integration of a Cropping Systems Simulation Model and a Relational Database for Simple Farm‐Scale Analyses
Authors: Bechini Luca , Stöckle Claudio O.
Published: August 2007

Agricultural simulation models are important tools in research, extension, policy formulation, and teaching. Their integration with relational databases allows carrying out complex and comprehensive data analyses of model inputs and outputs. In this article, we describe the integration of a dynamic cropping systems simulation model (CropSystVB) and a relational database (Microsoft Access), with the aim of developing a tool for simple applications at the farm scale. The data model, designed with the entity–relationship framework, represents the structure of the data and allows for organized and retrievable storage of inputs and outputs of the simulation model. In addition to standard CropSystVB's inputs (soil, crop, weather, management events), the integrated tool also requires input data to describe the nutrients produced by livestock and allows for spatially variable fields, soils, and management options. Farm simulation scenarios can be defined, including the actual and alternative configurations of animal breeds, rotations, and crop management. One or more rotations can be simulated for each scenario; each rotation is located on a homogeneous area (a field, or part of it, or a group of fields); each area is described with relevant soil and weather inputs. The Microsoft Access implementation of the integrated tool (www.bsyse.wsu.edu/cropsyst; verified 15 June 2007) includes a Visual Basic for Applications version of the model and tables and forms to store and manage data. An example simulation in an animal farm with six scenarios, obtained by the combination of three animal loads and two irrigation systems (surface and sprinkler), is presented to illustrate its use.
Sugarbeet Yield and Nitrogen Use Efficiency with Preplant Broadcast, Banded, or Point‐Injected Nitrogen Application
Authors: Stevens W. Bart , Blaylock Alan D. , Krall James M. , Hopkins Bryan G. , Ellsworth Jason W.
Published: August 2007

Rising fertilizer costs and environmental concerns have heightened the need to improve N management in furrow‐irrigated sugarbeet (Beta vulgaris L.) production. A study was conducted at two Wyoming locations to compare the effect of different preplant N placement strategies on yield, quality, and N use efficiency (NUE). Nitrogen was applied at rates from 0 to 358 kg ha−1 using three different placement strategies: broadcast and incorporated (BI), knife‐banded (KB) 18 cm from the seed row, or point‐injected (PI) 8 cm from the seed row. Placement had no consistent effect on root sucrose content. Point injection produced the greatest maximum predicted yield (YMAX) in five of six N responsive site‐years with an average advantage of 603 and 975 kg ha−1 sucrose compared to BI and KB, respectively. The amount of N required for maximum sucrose yield ranged from about 10 to 100 kg N ha−1 less for PI than for other placement methods. For site‐years where a response to N occurred, NUE was highest with PI, intermediate with KB (19% less than PI), and lowest with BI (28% less than PI). The advantage of PI, which placed N closer to the seed row than the other methods, was attributed to less leaching and greater uptake of N during early growth stages when the sugarbeet has little lateral root development. It was concluded that PI is an effective tool for maintaining high N concentration in the root zone for optimum early vegetative growth at lower N rates, thus improving NUE in sugarbeet production.
Arbuscular Mycorrhizal Fungi Associated with Green Gram in South India
Authors: Valsalakumar N. , Ray J. G. , Potty V. P.
Published: August 2007

Field studies are necessary to understand the abundance and type of indigenous arbuscular mycorrhizal (AM) fungi present in the rhizosphere. Green gram [Phaseolus aureus Roxb. (= Vigna radiata var. radiata)] is a major pulse crop of South India. A field study was conducted to identify the AM fungi associated with green gram under field conditions in this region. The rhizosphere soil samples from these fields were analyzed for AM fungal spores. Glomus mosseae, Glomus microcarpum, Gigaspora margarita, and Scutellospora sp. were identified as the AM fungi associated with green gram. Glomus mosseae was the most frequent AM fungal associate identified in 81%, G. microcarpum and G. margarita in 24% each, and Scutellospora sp. in 5% of the soils studied. The range of distribution varied from a single species of AM fungus to three species belonging to two genera in one sample. Correlations of spore count and percentage colonization for all the AM fungi on the crop in the field, along with soil parameters like pH, N, P, and K were studied. Significant negative correlation (P < 0.01) was obtained between percentage colonization and P. The pH and N were positively correlated (P < 0.01) with K. The study indicates involvement of factors other than soil nutrients in the distribution and sporulation of AM fungi.
The Magruder Plots: Untangling the Puzzle
Authors: Girma Kefyalew , Holtz Starr L. , Arnall Daryl B. , Tubaña Brenda S. , Raun William R.
Published: August 2007

Long‐term experiments play a vital role in revealing dynamic soil and weather processes that directly influence sustainable crop production and ecosystem health. The objective of this review paper is to present one of the oldest long‐term continuous winter wheat (Triticum aestivum L.) experiments, the Magruder Plots, and their contribution to the scientific community regarding questions of yield response to amendments, yield stability, percentage organic matter (OM) lost over time, soil nutrient status, microbial activity, weed population, and information on the economic return from winter wheat production. Alexander C. Magruder initiated the experiment in 1892 and is in progress to date. The original plot was started to evaluate wheat production on native prairie soils without fertilization. After 6 yr the principal investigator split the initial plot into two and fertilized one half with cattle manure. The experiment was then modified to include 10 treatments in 1930 by Dr. Horace J. Harper to answer several soil fertility related questions. Since 1947, six treatments have remained intact that evaluate simple combinations of manure, and inorganic N, P, K, and lime. Following 114 yr of continuous winter wheat production under conventional tillage, the check plot that has never received any fertilizer addition continues to produce wheat grain yields of >1 Mg ha−1. Despite the decline in soil organic matter from 4 to 1% during this time period, wheat grain yields continue to show slight increases with time, likely due to improved genetics. While continuous wheat without rotation is not recommended, this 114‐yr study documents the feasibility.
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.
Effects of Off-Pump Coronary Artery Bypass Grafting on Patient Outcome
Authors: Sohrabi Farrokh , Mispireta Luis A. , Fiocco Michael , Dibos Luis A. , Buescher Philip C. , Sloane Peter J.
Published: August 2007

Background

Cardiopulmonary bypass (CPB) is associated with postoperative myocardial stunning, hypothermia, formation of microemboli, and systemic inflammatory response syndrome, all of which may prolong recovery from coronary artery bypass grafting (CABG) surgery. This study sought to compare outcomes in patients undergoing CABG off pump versus on pump.

Methods

Outcomes, including mortality and several morbidities, were reviewed in 1,623 on-pump patients and 683 off-pump patients. Morbidities assessed included postoperative bleeding, incidence of multiorgan dysfunction, and neurologic complications. Chi-square and t-test analysis were used to determine statistical significance.

Results

Mortality was 42% lower in the off-pump group than the on-pump group. Both critical care and total hospital length of stay were significantly shorter in the off-pump group. The incidence of postoperative bleeding requiring transfusion or a return to the operating room was reduced by 29% in the off-pump group and the incidence of multiorgan dysfunction was reduced by 31%. The off-pump patients also presented a significantly lower incidence of cerebral vascular accidents and seizures than on-pump patients.

Conclusions

We conclude that there is an association between improved patient outcome and off-pump CABG surgery. The outcomes of this study show a statistically significant decrease in mortality, critical care length of stay, total hospital stay, incidence of bleeding requiring transfusion or return to the operating room, amount of blood transfused, incidence of multiorgan dysfunction, cerebral vascular accidents, and seizures in off-pump patients when compared with on-pump patients. Such results support the use of myocardial revascularization off pump as an alternative to CABG surgery on pump. CABG surgery off pump may allow a better postoperative clinical course in patients who are candidates for the procedure.
Detection of Free Antielastin Antibodies among Diabetic Children
Authors: Nicoloff George , Blazhev Alexer , Petrova Chaika , Christova Petkama , Jordanova-Laleva Pavlima , Dekov Dancho , Dorovski Plamen
Published: August 2007

Antibodies to elastin breakdown products are found in the serum of all human subjects and correlate with their respective serum peptide levels. The presence of these antielastin antibodies (AEAbs) and the corresponding antigens in circulation leads to the formation of circulating immune complexes (CICs). The aim of this study was to determine if the serum levels of free AEAbs (not bound in CICs) correlate with the development of vascular complications in diabetic children. To this end, we used a method for detecting immune complexes (complement inhibition factor [CIF]-enzyme-linked immunosorbent assay [ELISA]) in combination with an ELISA for detection of AEAbs. The levels of free immunoglobulin G (IgG) AEAbs were studied in the sera of 54 diabetic children (mean age 12.3 ± 4 years; diabetes duration 5.2 ± 3.7 years). Thirty-two of the children had vascular complications (group 1), and 22 were without vascular complications (group 2). Twenty healthy children (mean age 13.6 ± 4.2 years) were used as controls. The diabetics showed statistically significant higher levels of free AEAbs (0.490 E492 ± 0.244 E492 vs 0.307 E492 ± 0.081 E492; p = .02) compared with the control group. In group 1, free AEAbs showed statistically significant higher levels than controls (0.523 ± 0.269 vs 0.307 ± 0.081; p = .016). Eighteen of 54 (33%) patients were positive for free AEAbs (13 of 32 [41%] in group 1 and 5 of 22 [22%] in group 2). Free AEAb levels in all diabetics showed a correlation with systolic blood pressure ( r = .44; p = .01), diastolic blood pressure ( r = .46; p = .009), total cholesterol ( r = .33; p = .05), triglycerides ( r = .38; p = .03), high-density lipoprotein ( r = -.46; p = .009), serum fructose ( r = .43; p = .001), and microalbuminuria ( r = .41; p = .002). Patients who had vascular pathology showed a correlation of free AEAbs with microalbuminuria ( r = .434; p = .026), serum fructose ( r = .63; p = .0004), hemoglobin A1c ( r = .392; p = .043), and triglycerides ( r = .456; p = .025). These findings suggest that elevated levels of free IgG AEAbs are associated with the development of diabetic vascular complications in children.
Radionuclide-Based Insights into the Pathophysiology of Ischemic Heart Disease: Beyond Diagnosis
Authors: Michelena Hector I. , Vecker William A.
Published: August 2007

This review article discusses the historical origin of cardiac radionuclide-based methods, the physiologic background that justifies their existence, as well as the basic pathophysiologic concepts of coronary artery disease and their connection with the technologic design and application of these methods. Most importantly, this review discusses the important insights that these methods have provided to the understanding of the mechanisms of ischemia, risk stratification, and both treatment choice and treatment efficacy in ischemic heart disease.

Nuclear cardiology originated as an attempt to provide complementary physiologic information to the anatomic information provided by coronary angiography. To comprehend the design and applications of nuclear cardiology methods, one must have a basic understanding of coronary artery disease as an inflammatory process that may manifest as acute or chronic states. Basic concepts on myocyte metabolic pathways, coronary blood flow, ischemic cascade, ventricular remodeling, and ejection fraction become critical for this purpose. Insights into risk stratification may permit patient-tailored therapy approaches. Insights into prognosis have made nuclear cardiology a robust tool for outcome predictions, with an exceptionally high negative predictive value. Evaluation of prognosis in special patient populations such as diabetics has originated important pathophysiologic concepts. Most insights into phenomena such as myocardial hibernation, myocardial stunning, and viability have been generated by nuclear cardiology techniques. Finally, new applications of radionuclide-based methods such as molecular identification of “vulnerable” atherosclerotic plaques, “ischemic memory” using fatty acid imaging, and myocardial innervation imaging provide new avenues for insightful research.
Breaking the Translational Barriers: The Value of Integrating Biomedical Informatics and Translational Research
Authors: Payne Philip R. O. , Johnson Stephen B. , Starren Justin B. , Tilson Hugh H. , Dowdy David
Published: August 2007

The conduct of translational health research has become a vital national enterprise. However, multiple barriers prevent the effective translation of basic science discoveries into clinical and community practice. New information technology (IT) applications could help address these barriers. Unfortunately, owing to a combination of organizational, technical, and social factors, neither physician-investigators and research staff nor their clinical and community counterparts have harnessed such applications. Recently, at the request of the Institute of Medicine's Clinical Research Roundtable, a qualitative study of these factors was conducted at several leading academic medical centers. We explore the current status of IT in the translational research domain, describe the qualitative results, and conclude with a proposed set of initiatives to further increase the integration of IT into translational research.
Insulin Therapy, Glycemic Control, and Cardiovascular Risk Factors in Young Latin Americans with Type 2 Diabetes Mellitus
Authors: Avilés-Santa Larissa , Salinas Karin , Adams-Huet Beverley , Raskin Philip
Published: August 2007

Background

Type 2 diabetes has been linked to an increased risk of cardiovascular (CV) disease, but this risk has not been well documented in young patients, especially of Latin American descent. Also, the potential CV benefits of insulin therapy have not been evaluated in young patients with type 2 diabetes. The objectives of this study were to determine any gender-related difference in the presence of CV risk factors in young Latin Americans with poorly controlled type 2 diabetes and the effect of intensive insulin therapy on these CV risk factors.

Methods and Results

Fifty-seven Latin American patients with type 2 diabetes between the ages 18 and 45 years were evaluated at baseline. All women were premenopausal and had regular menstrual periods. The mean body mass index (BMI) was > 30 kg/m2 in both genders. Percent body fat, percent hemoglobin A1c, and lipoprotein profiles were similar between genders. Highly sensitive C-reactive protein (CRP) levels were elevated and similar between genders (p = .4). Leukocyte adhesion molecules (intercellular adhesion molecule 1, vascular adhesion molecule 1, E-selectin) and monocyte chemoattractant protein 1 were elevated, whereas adiponectin levels were below normal in both gender groups. Urinary albumin excretion was similar between genders and did not show any relationship with any of the variables. In women, there was a direct relationship between waist circumference and high-sensitivity CRP levels (rho = .53, p = .01). No other significant relationships were observed. Eighteen Latin American patients with type 2 diabetes completed up to 104 weeks of postintervention with insulin monotherapy. In these patients, glycemic, lipoprotein, and anthropometric measurements were obtained every 12 weeks. Highly sensitive CRP, leukocyte adhesion molecules, and urinary albumin excretion, among other tests, were obtained every 52 weeks. At 52 and 104 weeks, body weight, BMI, waist circumference, and percent body fat increased in a parallel and significant manner. Despite a significant decrease in percent hemoglobin A1c (22.2%; p = < .0001), lipid and lipoprotein profiles, highly sensitive CRP, leukocyte adhesion molecules, and other nontraditional CV risk factors did not change significantly.

Conclusions

In young, obese, Latino type 2 diabetic patients, improvement in glycemic control with insulin monotherapy was not associated with a parallel improvement in markers of vascular inflammation. Premenopausal Latino women with uncontrolled type 2 diabetes have CV risks comparable to Latino diabetic men of the same age. Obesity and underlying insulin resistance may counteract the potential CV benefits associated with insulin therapy in lean diabetic patients. Weight loss could be a potential therapeutic modality to improve CV risk in Latino type 2 diabetic patients, especially women.