bluuebunny/crossref_metadata_2025 huggingface dataset:
Postprandial lipemia in men with metabolic syndrome, hypertensives and healthy subjects
Authors: Kolovou Genovefa D , Anagnostopoulou Katherine K , Pavlidis Antonis N , Salpea Klelia D , Iraklianou Stella A , Tsarpalis Konstantinos , Damaskos Dimitris S , Manolis Athanasios , Cokkinos Dennis V
Published: October 2005

Background

The metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects.

Results

OFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG ≥ 150 [MetS+TG, (n = 22)] or <150 mg/dl [MetS-TG (n = 11)], and into those with or without hypertension [MetS+HTN (n = 24), MetS-HTN (n = 9), respectively]. TG concentrations were measured before and at 4, 6 and 8 h after OFTT and the postprandial response was quantified using the area under the curve (AUC) for TG.

The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 ± 1016 vs. 1620 ± 494 and 1019 ± 280, respectively, p ≤ 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001).

Conclusion

Fasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.
Potential targets of transforming growth factor-beta1 during inhibition of oocyte maturation in zebrafish
Authors: Kohli Gurneet , Clelland Eric , Peng Chun
Published: October 2005

Background

TGF-beta is a multifunctional growth factor involved in regulating a variety of cellular activities. Unlike mammals, the function of TGF-beta in the reproduction of lower vertebrates, such as fish, is not clear. Recently, we showed that TGF-beta1 inhibits gonadotropin- and 17alpha, 20beta-dihydroxyprogesterone (DHP)-induced maturation in zebrafish. The aim of the present study was to investigate the mechanisms underlying this action.

Method

To determine if the effect of TGF-beta1 on oocyte maturation involves transcription and/or translation, ovarian follicles were pre-treated with actinomycin D, a blocker of transcription, and cyclohexamide, an inhibitor of translation, and incubated with hCG or DHP, either alone or in combination with TGF-beta1 and oocyte maturation scored. To determine the effect of TGF-beta1 on mRNA levels of several key effectors of oocyte maturation, three sets of experiments were performed. First, follicles were treated with control medium or TGF-beta1 for 2, 6, 12, and 24 h. Second, follicles were treated with different concentrations of TGF-beta1 (0 to 10 ng/ml) for 18 h. Third, follicles were incubated with hCG in the absence or presence of TGF-beta1 for 18 h. At the end of each experiment, total RNA was extracted and reverse transcribed. PCR using primers specific for 20beta-hydroxysteroid dehydrogenase (20beta-HSD) which is involved in DHP production, follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), the two forms of membrane progestin receptor: mPR-alpha and mPR-beta, as well as GAPDH (control), were performed.

Results

Treatment with actinomycin D, a blocker of transcription, reduced the inhibitory effect of TGF-beta1 on DHP-induced oocyte maturation, indicating that the inhibitory action of TGF-beta1 is in part due to regulation of gene transcription. Treatment with TGF-beta1 caused a dose and time-dependent decrease in mRNA levels of 20beta-HSD, LHR and mPR-beta in follicles. On the other hand, TGF-beta1 had no effect on mPR-alpha mRNA expression and increased FSHR mRNA levels. Furthermore, hCG upregulated 20beta-HSD, LHR and mPR-beta mRNA levels, but this stimulatory effect was blocked by TGF-beta1.

Conclusion

These findings suggest that TGF-beta1 acts at multiple sites, including LHR, 20beta-HSD and mPR-beta, to inhibit zebrafish oocyte maturation.
Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors)
Authors: Krasowski Matthew D , Yasuda Kazuto , Hagey Lee R , Schuetz Erin G
Published: October 2005

Background

The nuclear hormone receptor (NR) superfamily complement in humans is composed of 48 genes with diverse roles in metabolic homeostasis, development, and detoxification. In general, NRs are strongly conserved between vertebrate species, and few examples of molecular adaptation (positive selection) within this superfamily have been demonstrated. Previous studies utilizing two-species comparisons reveal strong purifying (negative) selection of most NR genes, with two possible exceptions being the ligand-binding domains (LBDs) of the pregnane X receptor (PXR, NR1I2) and the constitutive androstane receptor (CAR, NR1I3), two proteins involved in the regulation of toxic compound metabolism and elimination. The aim of this study was to apply detailed phylogenetic analysis using maximum likelihood methods to theentirecomplement of genes in the vertebrate NR superfamily. Analyses were carried out both across all vertebrates and limited to mammals and also separately for the two major domains of NRs, the DNA-binding domain (DBD) and LBD, in addition to the full-length sequences. Additional functional data is also reported for activation of PXR and the vitamin D receptor (VDR; NR1I1) to gain further insight into the evolution of the NR1I subfamily.

Results

The NR genes appear to be subject to strong purifying selection, particularly in the DBDs. Estimates of the ratio of the non-synonymous to synonymous nucleotide substitution rates (the ω ratio) revealed that only the PXR LBD had a sub-population of codons with an estimated ω ratio greater than 1. CAR was also unusual in showing high relative ω ratios in both the DBD and LBD, a finding that may relate to the recent appearance of the CAR gene (presumably by duplication of a pre-mammalian PXR gene) just prior to the evolution of mammals. Functional analyses of the NR1I subfamily show that human and zebrafish PXRs show similar activation by steroid hormones and early bile salts, properties not shared by sea lamprey, mouse, or human VDRs, or byXenopus laevisPXRs.

Conclusion

NR genes generally show strong sequence conservation and little evidence for positive selection. The main exceptions are PXR and CAR, genes that may have adapted to cross-species differences in toxic compound exposure.
Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms
Authors: Tachibana Keisuke , Kobayashi Yumi , Tanaka Toshiya , Tagami Masayuki , Sugiyama Akira , Katayama Tatsuya , Ueda Chihiro , Yamasaki Daisuke , Ishimoto Kenji , Sumitomo Mikako , Uchiyama Yasutoshi , Kohro Takahide , Sakai Juro , Hamakubo Takao , Kodama Tatsuhiko , Doi Takefumi
Published: October 2005

Background

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and commonly play an important role in the regulation of lipid homeostasis. To identify human PPARs-responsive genes, we established tetracycline-regulated human hepatoblastoma cell lines that can be induced to express each human PPAR and investigated the gene expression profiles of these cells.

Results

The expression of each introduced PPAR gene was investigated using the various concentrations of doxycycline in the culture media. We found that the expression of each PPAR subtype was tightly controlled by the concentration of doxycycline in these established cell lines. DNA microarray analyses using these cell lines were performed with or without adding each subtype ligand and provided much important information on the PPAR target genes involved in lipid metabolism, transport, storage and other activities. Interestingly, it was noted that while ligand-activated PPARδ induced target gene expression, unliganded PPARδ repressed these genes. The real-time RT-PCR was used to verify the altered expression of selected genes by PPARs and we found that these genes were induced to express in the same pattern as detected in the microarray analyses. Furthermore, we analysed the 5'-flanking region of the human adipose differentiation-related protein (adrp) gene that responded to all subtypes of PPARs. From the detailed analyses by reporter assays, the EMSAs, and ChIP assays, we determined the functional PPRE of the human adrp gene.

Conclusion

The results suggest that these cell lines are important tools used to identify the human PPARs-responsive genes.
Interleukin-1β induced vascular permeability is dependent on induction of endothelial Tissue Factor (TF) activity
Authors: Puhlmann Markus , Weinreich David M , Farma Jeffrey M , Carroll Nancy M , Turner Ewa M , Alexander H Richard
Published: October 2005

IL-1β is a pleotropic cytokine that may mediate increased procoagulant activity and permeability in endothelial tissue during inflammatory conditions. The procoagulant effects of IL-1β are mediated through induction of tissue factor (TF) but its alterations on vascular permeability are not well characterized. We found that IL-1β induced a rapid and dose-dependent increase in TF activity in human umbilical vein endothelial cells (ECs) under routine culture conditions. However, IL-1β caused a rapid and marked increase in permeability across confluent EC monolayers using a two-compartmentin vitromodel only in the presence of factor VIII-deficient plasma that was completely abrogated by neutralizing anti-TF antibody pre-treatment.In vitropermeability was associated with loss of EC surface expression of VE-cadherin and contraction of F-actin cytoskeletal elements that resulted in EC intercellular gap formation. These data demonstrate that IL-1β induces marked changes in permeability across activated endothelium via a TF dependent mechanism and suggest that modulation of TF activity may represent a strategy to treat various acute and chronic inflammatory conditions mediated by this cytokine.
Uncertainty principle of genetic information in a living cell
Authors: Strippoli Pierluigi , Canaider Silvia , Noferini Francesco , D'Addabbo Pietro , Vitale Lorenza , Facchin Federica , Lenzi Luca , Casadei Raffaella , Carinci Paolo , Zannotti Maria , Frabetti Flavia
Published: October 2005

Background

Formal description of a cell's genetic information should provide the number of DNA molecules in that cell and their complete nucleotide sequences. We pose the formal problem: can the genome sequence forming the genotype of a given living cell be known with absolute certainty so that the cell's behaviour (phenotype) can be correlated to that genetic information? To answer this question, we propose a series of thought experiments.

Results

We show that the genome sequence of any actual living cell cannot physically be known with absolute certainty, independently of the method used. There is an associated uncertainty, in terms of base pairs, equal to or greater than μs (where μ is the mutation rate of the cell type and s is the cell's genome size).

Conclusion

This finding establishes an "uncertainty principle" in genetics for the first time, and its analogy with the Heisenberg uncertainty principle in physics is discussed. The genetic information that makes living cells work is thus better represented by a probabilistic model rather than as a completely defined object.
Volume of the effect compartment in simulations of neuromuscular block
Authors: Nigrovic Vladimir , Proost Johannes H , Amann Anton , Bhatt Shashi B
Published: October 2005

Background

The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants.

Methods

The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment.

Results

The simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities.

Conclusion

An experimental design to estimate the volume of the effect compartment is suggested.
Evaluation of a strict protocol approach in managing women with severe disease due to hypertension in pregnancy: A before and after study
Authors: Lombaard Hennie , Pattinson Robert C , Backer Fèbè , Macdonald Peter
Published: October 2005

Background

To evaluate whether the introduction of a strict protocol based on the systemic evaluation of critically ill pregnant women with complications of hypertension affected the outcome of those women.

Method

Study group: Indigent South African women managed in the tertiary hospitals of the Pretoria Academic Complex. Since 1997 a standard definition of women with severe acute maternal morbidity (SAMM), also referred to as a Nearmiss, has been used in the Pretoria Academic Complex. All cases of SAMM and maternal deaths (MD) were entered on the Maternal Morbidity and Mortality Audit System programme (MaMMAS). A comparison of outcome of severely ill women who had complications of hypertension in pregnancy was performed between 1997–1998 (original protocol) and 2002–2003 (strict protocol). Data include women referred from outside the Pretoria Academic Complex area to the tertiary hospitals.

Results

Between 1997–1998 there were 79 women with SAMM and 18 maternal deaths due to complications of hypertension, compared with 91 women with SAMM and 13 maternal deaths in 2002–2003. The mortality index (MI) declined from 18.6% to 12.5% (OR 0.62, 95% CI 0.27–1.45). Statistically significant fewer women had renal failure (RR 0.37, 95% CI 0.21 – 0.66) and cerebral complications (RR 0.52, 95%CI 0.34 – 0.81) during the second period, and liver dysfunction (RR 0.27 95%CI 0.06 – 1.25) tended to be lower. However, there tended to be an increase in the number of women, who had immune system failure (RR 4.2 95%CI 0.93 – 18.94) and respiratory failure (RR 1.42 95%CI 0.88 – 2.29) although it did not reach significance. Cardiac failure remained constant (RR 0.84 95%CI 0.54 – 1.30).

Conclusion

The strict protocol approach based on the systemic evaluation of severely ill pregnant women with complications of hypertension and an intensive, regular feedback mechanism has been associated with a reduction in the number of patients with renal failure and cerebral compromise.
Biodemographic perspectives for epidemiologists
Authors: Olshansky S Jay , Grant Mark , Brody Jacob , Carnes Bruce A
Published: October 2005

A new scientific discipline arose in the late 20th century known as biodemography. When applied to aging, biodemography is the scientific study of common age patterns and causes of death observed among humans and other sexually reproducing species and the biological forces that contribute to them. Biodemography is interdisciplinary, involving a combination of the population sciences and such fields as molecular and evolutionary biology. Researchers in this emerging field have discovered attributes of aging and death in humans that may very well change the way epidemiologists view and study the causes and expression of disease. In this paper, the biodemography of aging is introduced in light of traditional epidemiologic models of disease causation and death.
The development of postural strategies in children: a factorial design study
Authors: Schmid Maurizio , Conforto Silvia , Lopez Luisa , Renzi Paolo , D'Alessio Tommaso
Published: October 2005

Background

The present study investigates balance control mechanisms, their variations with the absence of visual input, and their development in children from 7 to 11 years old, in order to provide insights on the development of balance control in the pediatric population.

Methods

Posturographic data were recorded during 60 s trials administered on a sample population of 148 primary school children while stepping and then quietly standing on a force plate in two different vision conditions: eyes closed and eyes open. The extraction of posturographic parameters on the quiet standing phase of the experiment was preceded by the implementation of an algorithm to identify the settling time after stepping on the force plate. The effect of different conditions on posturographic parameters was tested with a two-way ANOVA (Age × Vision), and the corresponding eyes-closed/eyes-open (Romberg) Ratios underwent a one-way ANOVA.

Results

Several posturographic measures were found to be sensitive to testing condition (eyes closed vs. eyes open) and some of them to age and anthropometric parameters. The latter relationship did not explain all the data variability with age. An evident modification of postural strategy was observed between 7 and 11 years old children.

Conclusion

Simple measures extracted from posturographic signals resulted sensitive to vision and age: data acquired from force plate made it possible to confirm the hypothesis of the development of postural strategies in children as a more mature selection and re-weighting of proprioceptive inputs to postural control in absence of visual input.
Follicular fluid levels of vascular endothelial growth factor and early corpus luteum function during assisted reproductive technology cycles
Authors: Coppola F , Ferrari B , Barusi L , Caccavari V , Salvarani MC , Piantelli G
Published: October 2005

Background

The relation between vascular endothelial growth factor (VEGF) and early luteal function has rarely been proven in humans. The purpose of this study was to define the relation between follicular fluid concentrations of VEGF (FF VEGF) and early luteal function at the preimplantation stage during assisted reproductive technology (ART) cycles.

Methods

71 women were divided into two groups, based on reproductive outcome: women who became pregnant after embryo transfer (ET) (n = 18, Group A) and non-pregnant women (n = 53, Group B). Serum progesterone (Se P) and inhibin A on ET day, and FF VEGF levels were measured in all women. Data were expressed as mean ± standard deviation. Statistical analysis was performed using Excel Office 98 for Student's t-test, linear regression test and chi-square test. A p value of < 0.05 was considered statistically significant.

Results

The groups were comparable for age, ovarian reserve, number and quality of the oocytes retrieved and of the embryos obtained and transferred. FF VEGF levels were increased (4235 ± 1433 vs 3432 ± 1231 pg/ml), while Se P and inhibin A levels were significantly reduced (83.1 ± 34.1 vs 112.0 ± 58.8 ng/ml and 397.4 ± 223 vs 533.5 ± 283 pg/ml, respectively) in the non-pregnant group and were negatively correlated with FF VEGF (r = -0.482, p < 0.05; r = -0.468, p < 0.05) only in pregnant women.

Conclusion

Much has to be learned about the regulation and role of VEGF during the early luteal phase. We advance the hypothesis that the existence of a negative correlation between FF VEGF/Se P and FF VEGF/inhibin A in pregnant women might indicate the existence of a normal VEGF-mediated paracrine response when Se P and inhibin A levels are decreased. Excess production of FF VEGF and the absence of a correlation between FF VEGF/Se P and FF VEGF/inhibin A in non-pregnant women may be a paracrine reaction to immature luteal vasculature, resulting in luteal dysfunction.
The circumventricular organs participate in the immunopathogenesis of experimental autoimmune encephalomyelitis
Authors: Schulz Martina , Engelhardt Britta
Published: October 2005

Background

During inflammatory conditions of the central nervous system (CNS), such as in multiple sclerosis or in its animal model, experimental autoimmune encephalomyelitis (EAE), immune cells migrate from the blood stream into the CNS parenchyma and into the cerebrospinal fluid (CSF) spaces. The endothelial blood-brain barrier (BBB) has been considered the most obvious entry site for circulating immune cells. Recently, the choroid plexus has been considered as an alternative entry site for circulating lymphocytes into the CSF. The choroid plexus, belongs to the circumventricular organs (CVOs) localized in the walls of the ventricles. Other CVOs, which similar to the choroid plexus lack an endothelial BBB, have not been considered as possible entry sites for immune cells into the CNS parenchyma or the CSF. Here we asked, whether CVOs are involved in the recruitment of inflammatory cells into the brain during EAE.

Methods

We performed an extensive immunohistological study on the area postrema (AP), the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT) and the median eminence (ME) in frozen brain sections from healthy SJL mice and mice suffering from EAE. Expression of cell adhesion molecules, the presence of leukocyte subpopulations and the detection of major histocompatibility complex antigen expression was compared.

Results

Similar changes were observed for all four CVOs included in this study. During EAE significantly increased numbers of CD45+ leukocytes were detected within the four CVOs investigated, the majority of which stained positive for the macrophage markers F4/80 and Mac-1. The adhesion molecules ICAM-1 and VCAM-1 were upregulated on the fenestrated capillaries within the CVOs. A considerable upregulation of MHC class I throughout the CVOs and positive immunostaining for MHC class II on perivascular cells additionally documented the immune activation of the CVOs during EAE. A significant enrichment of inflammatory infiltrates was observed in close vicinity to the CVOs.

Conclusion

Our data indicate that the CVOs are a site for the entry of immune cells into the CNS and CSF and consequently are involved in the inflammatory process in the CNS during EAE.
Low back pain risk factors in a large rural Australian Aboriginal community. An opportunity for managing co-morbidities?
Authors: Vindigni Dein , Walker Bruce F , Jamison Jennifer R , Da Costa Cliff , Parkinson Lynne , Blunden Steve
Published: October 2005

Background

Low back pain (LBP) is the most prevalent musculo-skeletal condition in rural and remote Australian Aboriginal communities. Smoking, physical inactivity and obesity are also prevalent amongst Indigenous people contributing to lifestyle diseases and concurrently to the high burden of low back pain.

Objectives

This paper aims to examine the association between LBP and modifiable risk factors in a large rural Indigenous community as a basis for informing a musculo-skeletal and related health promotion program.

Methods

A community Advisory Group (CAG) comprising Elders, Aboriginal Health Workers, academics, nurses, a general practitioner and chiropractors assisted in the development of measures to assess self-reported musculo-skeletal conditions including LBP risk factors. The Kempsey survey included a community-based survey administered by Aboriginal Health Workers followed by a clinical assessment conducted by chiropractors.

Results

Age and gender characteristics of this Indigenous sample (n = 189) were comparable to those reported in previous Australian Bureau of Statistics (ABS) studies of the broader Indigenous population. A history of traumatic events was highly prevalent in the community, as were occupational risk factors. Thirty-four percent of participants reported a previous history of LBP. Sporting injuries were associated with multiple musculo-skeletal conditions, including LBP. Those reporting high levels of pain were often overweight or obese and obesity was associated with self-reported low back strain. Common barriers to medical management of LBP included an attitude of being able to cope with pain, poor health, and the lack of affordable and appropriate health care services.

Though many of the modifiable risk factors known to be associated with LBP were highly prevalent in this study, none of these were statistically associated with LBP.

Conclusion

Addressing particular modifiable risk factors associated with LBP such as smoking, physical inactivity and obesity may also present a wider opportunity to prevent and manage the high burden of illness imposed by co-morbidities such as heart disease and type-2 diabetes.
Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells
Authors: Baugher Paige J , Krishnamoorthy Lakshmi , Price Janet E , Dharmawardhane Surangani F
Published: October 2005

Introduction

The metastatic progression of cancer is a direct result of the disregulation of numerous cellular signaling pathways, including those associated with adhesion, migration, and invasion. Members of the Rac family of small GTPases are known to act as regulators of actin cytoskeletal structures and strongly influence the cellular processes of integrin-mediated adhesion and migration. Even though hyperactivated Rac proteins have been shown to influence metastatic processes, these proteins have never been directly linked to metastatic progression.

Methods

To investigate a role for Rac and Cdc42 in metastatic breast cancer cell invasion and migration, relative endogenous Rac or Cdc42 activity was determined in a panel of metastatic variants of the MDA-MB-435 metastatic human breast cancer cell line using a p21-binding domain-PAK pull down assay. To investigate the migratory and invasive potential of the Rac isoforms in human breast cancer, namely Rac1 and the subsequently cloned Rac3, we stably expressed either dominant active Rac1 or dominant active Rac3 into the least metastatic cell variant. Dominant negative Rac1 or dominant negative Rac3 were stably expressed in the most metastatic cell variant. Cell lines expressing mutant Rac1 or Rac3 were analyzed using in vitro adhesion, migration and invasion assays.

Results

We show that increased activation of Rac proteins directly correlates with increasing metastatic potential in a panel of cell variants derived from a single metastatic breast cancer cell line (MDA-MB-435). The same correlation could not be found with activated Cdc42. Expression of a dominant active Rac1 or a dominant active Rac3 resulted in a more invasive and motile phenotype. Moreover, expression of either dominant negative Rac1 or dominant negative Rac3 into the most metastatic cell variant resulted in decreased invasive and motile properties.

Conclusion

This study correlates endogenous Rac activity with high metastatic potential and implicates Rac in the regulation of cell migration and invasion in metastatic breast cancer cells. Taken together, these results suggest a role for both the Rac1 and Rac3 GTPases in human breast cancer progression.
Central venous catheter-related infection in a prospective and observational study of 2,595 catheters
Authors: Lorente Leonardo , Henry Christophe , Martín María M , Jiménez Alejandro , Mora María L
Published: October 2005

Introduction

Central venous catheterization is commonly used in critically ill patients and may cause different complications, including infection. Although there are many studies about CVC-related infection, very few have analyzed it in detail. The objective of this study was to analyze the incidence of catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) with central venous catheters (CVCs) according to different access sites.

Methods

This is a prospective and observational study, conducted in a 24-bed medical surgical intensive care unit of a 650-bed university hospital. All consecutive patients admitted to the ICU during 3 years (1 May 2000 and 30 April 2003) were included.

Results

The study included 2,018 patients. The number of CVCs and days of catheterization duration were: global, 2,595 and 18,999; subclavian, 917 and 8,239; jugular, 1,390 and 8,361; femoral, 288 and 2,399. CRLI incidence density was statistically higher for femoral than for jugular (15.83 versus 7.65, p < 0.001) and subclavian (15.83 versus 1.57, p < 0.001) accesses, and higher for jugular than for subclavian access (7.65 versus 1.57, p < 0.001). CRBSI incidence density was statistically higher for femoral than for jugular (8.34 versus 2.99, p = 0.002) and subclavian (8.34 versus 0.97, p < 0.001) accesses, and higher for jugular than for subclavian access (2.99 versus 0.97, p = 0.005).

Conclusion

Our results suggest that the order for punction, to minimize the CVC-related infection risk, should be subclavian (first order), jugular (second order) and femoral vein (third order).
A catalog of stability-associated sequence elements in 3' UTRs of yeast mRNAs
Authors: Shalgi Reut , Lapidot Michal , Shamir Ron , Pilpel Yitzhak
Published: October 2005

Background

In recent years, intensive computational efforts have been directed towards the discovery of promoter motifs that correlate with mRNA expression profiles. Nevertheless, it is still not always possible to predict steady-state mRNA expression levels based on promoter signals alone, suggesting that other factors may be involved. Other genic regions, in particular 3' UTRs, which are known to exert regulatory effects especially through controlling RNA stability and localization, were less comprehensively investigated, and deciphering regulatory motifs within them is thus crucial.

Results

By analyzing 3' UTR sequences and mRNA decay profiles of Saccharomyces cerevisiae genes, we derived a catalog of 53 sequence motifs that may be implicated in stabilization or destabilization of mRNAs. Some of the motifs correspond to known RNA-binding protein sites, and one of them may act in destabilization of ribosome biogenesis genes during stress response. In addition, we present for the first time a catalog of 23 motifs associated with subcellular localization. A significant proportion of the 3' UTR motifs is highly conserved in orthologous yeast genes, and some of the motifs are strikingly similar to recently published mammalian 3' UTR motifs. We classified all genes into those regulated only at transcription initiation level, only at degradation level, and those regulated by a combination of both. Interestingly, different biological functionalities and expression patterns correspond to such classification.

Conclusion

The present motif catalogs are a first step towards the understanding of the regulation of mRNA degradation and subcellular localization, two important processes which - together with transcription regulation - determine the cell transcriptome.
The combined CXCR1/CXCR2 antagonist CXCL8(3–74)K11R/G31P blocks neutrophil infiltration, pyrexia, and pulmonary vascular pathology in endotoxemic animals
Authors: Gordon John R , Li Fang , Zhang Xiaobei , Wang Wenjun , Zhao Xixing , Nayyar Aarti
Published: October 2005

CXC chemokine receptor 2 (CXCR2) antagonism alone can reduce neutrophil infiltration of some inflammatory sites, but the CXCR1 and CXCR2 critically regulate neutrophil responses to Glu-Leu-Arg-CXC chemokines. Herein, we assessed a combined CXCR1/CXCR2 antagonist, CXC chemokine ligand 8(3–74) [CXCL8(3–74)]K11R/G31P, for its ability to blunt neutrophil-influx and ancillary pathology in severe endotoxemia. Guinea pigs challenged via the airways with Escherichia coli lipopolysaccharide (LPS; 5 μg/kg) were given CXCL8(3–74)K11R/G31P (subcutaneously) before or after the onset of symptoms. The airways of the LPS-challenged animals contained high levels of endogenous pyrogens interleukin (IL)-1 and tumor necrosis factor (TNF) at 2–4 h, and the animals developed pyrexia, which peaked at ≈6 h; strong pulmonary, neutrophilic inflammation; and marked pleural hemorrhagic consolidation, as assessed at ≈15 h. CXCL8(3–74)K11R/G31P treatment before LPS challenge reduced lung pleural hemorrhagic consolidation and airway neutrophilia by >90% and essentially abrogated the IL-1, TNF, and fever responses. When given 3 or 6 h after LPS, CXCL8(3–74)K11R/G31P reduced pulmonary neutrophilia by up to 85% and pleural hemorrhagic consolidation by 50–85%. The 3-h treatment reduced the 6- to 24-h fever response to background. Delays of 6 or 9 h in beginning treatment had significant effects on the fever decay curve, but only the 6-h treatment had a significant effect on the 24-h fever. These results indicate that combined CXCR1/CXCR2 antagonism can have significant therapeutic effects on pulmonary inflammation and hemorrhage, as well as pyrexia in endotoxemic animals.
High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation Does Not Increase the Risk of Second Neoplasms for Patients With Hodgkin's Lymphoma: A Comparison of Conventional Therapy Alone Versus Conventional Therapy Followed by Autologous Hematopoietic Stem-Cell Transplantation
Authors: Forrest Donna L. , Hogge Donna E. , Nevill Thomas J. , Nantel Stephen H. , Barnett Michael J. , Shepherd John D. , Sutherland Heather J. , Toze Cynthia L. , Smith Clayton A. , Lavoie Julye C. , Song Kevin W. , Voss Nicholas J. , Gascoyne Randy D. , Connors Joseph M.
Published: October 2005

Purpose

To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence.

Patients and Methods

We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT.

Results

The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age ≥ 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged ≥ 35 years (P = .03) and stage III/IV (P = .04).

Conclusion

Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.
Epidermal Growth Factor Receptor Mutations and Gene Amplification in Non–Small-Cell Lung Cancer: Molecular Analysis of the IDEAL/INTACT Gefitinib Trials
Authors: Bell Daphne W. , Lynch Thomas J. , Haserlat Sara M. , Harris Patricia L. , Okimoto Ross A. , Brannigan Brian W. , Sgroi Dennis C. , Muir Beth , Riemenschneider Markus J. , Iacona Renee Bailey , Krebs Annetta D. , Johnson David H. , Giaccone Giuseppe , Herbst Roy S. , Manegold Christian , Fukuoka Masahiro , Kris Mark G. , Baselga José , Ochs Judith S. , Haber Daniel A.
Published: October 2005

Purpose

Most cases of non–small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib.

Patients and Methods

We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC.

Results

EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of NSCLC. In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P = .001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype.

Conclusion

EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers.
Competitive Immunoassay Using Capillary Electrophoresis with a Chemiluminescence Detector
Authors: Tsukagoshi Kazuhiko , Jinno Naoya , Toguchi Kae , Nakajima Riichiro
Published: October 2005

We have proposed competitive immunoassay using capillary electrophoresis (CE) with a chemiluminescence (CL) detector, in which a small amount of sample (ca. 20 μL) is required for analysis. Human serum albumin (HSA) and anti-human serum IgG (anti-HSA) were used for immune reaction as a model. A luminol and hydrogen peroxide CL reaction was adopted, and HSA was labeled with isoluminol isothiocyanate (ILITC) for competitive immunoassay. The reactant after the immune reaction was directly subjected to CE with the CL detector, where the labeled HSA was easily and rapidly separated and detected. The amount of labeled HSA indicated a good relationship to that of HSA as an analyte through the immune reaction. The HSA was determined over the range of 0.2–1.2 μM with a detection limit of 0.1 μM (S/N = 3). The present method features high sensitivity, a small sample volume, and easy and rapid operation. The method also shows the possibility to analyze a specific protein in a serum sample.
Dividend Taxation and Corporate Governance
Authors: Morck Randall , Yeung Bernard
Published: October 2005

In 2003, the United States enacted a tax reform that reduced, but did not eliminate, individual dividend income taxes. Cutting the dividend tax deprives corporate insiders of a justification for retaining earnings to build unprofitable corporate empires. But not eliminating it entirely preserves an advantage for institutional investors, who can put pressure on underperforming managers. This balance is broadly appropriate in the United States—whose large companies are freestanding and widely held. In addition, preserving the existing tax on intercorporate dividends, in place since the Roosevelt era, discourages the pyramidal corporate groups commonplace in other countries, and preserves America's large corporate sector of free-standing widely held firms.
Political Selection
Authors: Besley Timothy
Published: October 2005

Almost every major episode of economic change over the past 200 years of political history has been associated with key personalities coming to power with a commitment to these changes. But if such dynamic leaders are so important, then we need to understand how they come to hold the reins of power. This outcome could be viewed as largely the product of random events colored by idiosyncratic personalities and chance encounters. However, at least some role must be given to the underlying institutional structure, which has a more systematic influence on who rises to the top. Thus, it is essential to understand how political selection works.
Recommendations for Further Reading
Authors: Taylor Timothy
Published: October 2005

This section will list readings that may be especially useful to teachers of undergraduate economics, as well as other articles that are of broader cultural interest. In general, the articles chosen will be expository or integrative and not focus on original research. If you write or read an appropriate article, please send a copy of the article (and possibly a few sentences describing it) to Timothy Taylor, c/o Journal of Economic Perspectives, Macalester College, 1600 Grand Ave., Saint Paul, Minnesota, MN 55105.
Steven D. Levitt: 2003 John Bates Clark Medalist
Authors: Poterba James M
Published: October 2005

Steve's Clark Medal citation mentions his path-breaking contributions to the economics of crime and to the political economy of campaign finance. This paper describes Steve's research in each of these areas, as well as his contributions on a range of other topics. It identifies the substantive themes as well as the methodological patterns that run through Steve's research, and it describes the economic issues that have been informed by his analysis.
Adam Smith's Theory of Moral Sentiments: On Morals and Why They Matter to a Liberal Society of Free People and Free Markets
Authors: Evensky Jerry
Published: October 2005

This essay describes Smith's analysis of ethics in his Theory of Moral Sentiments: the interaction of our nature and our nurturing that makes common civic ethics possible and the dynamic interaction of individuals and extant societal constructions that can lead to ever more mature systems of civic ethics and thus toward those conditions necessary for a constructive, sustainable liberal system.
The Constitutional Dilemma of Economic Liberty
Authors: Weingast Barry R
Published: October 2005

This paper studies the problem of self-enforcing constitutions, addressing the question, how do some constitutions provide incentives for political officials to abide by the constraints announced in the constitution? To understand the mechanisms underlying successful constitutions, the paper begins by exploring a simple society facing the dilemma of policing the government: a sovereign, who controls the government, and two citizens. It then moves to a discussion of how constitutions are often formed out of crises, with some more detailed discussion of two main examples: England's Glorious Revolution of 1688 and the U.S. Constitution.
History Lessons: The End of American Exceptionalism? Mobility in the United States Since 1850
Authors: Ferrie Joseph P
Published: October 2005

New longitudinal data on individuals linked across nineteenth century U.S. censuses document the geographic and occupational mobility of more than 75,000 Americans from the 1850s to the 1920s. Together with longitudinal data for more recent years, these data make possible for the first time systematic comparisons of mobility over the last 150 years of American economic development, as well as cross-national comparisons for the nineteenth century. The U.S. was a substantially more mobile economy than Britain between 1850 and 1880. But both intergenerational occupational mobility and geographic mobility have declined in the U.S. since the beginning of the twentieth century, leaving much less apparent two aspects of the “American Exceptionalism” noted by nineteenth century observers.
Distinguished Lecture on Economics in Government: What We Don't Know Could Hurt Us: Some Reflections on the Measurement of Economic Activity
Authors: Abraham Katharine G
Published: October 2005

The routine production of U.S. economic statistics dates back to the early part of the twentieth century. But in recent decades, as services output has continued to expand a system of economic statistics that had been designed during the manufacturing era began to seem increasingly outdated. Over the past decade, the statistical agencies have done yeoman work to expand the availability and quality of service sector statistics, but the task is far from completed. Moreover, the traditional accounting framework for economic statistics has focused almost exclusively on market transactions. Looking ahead, more comprehensive measurement of productive activities, however they may be organized, must be a priority.
Law, Endowments and Property Rights
Authors: Levine Ross
Published: October 2005

While scholars have hypothesized about the sources of variation in property rights for over 2500 years, it is only very recently that researchers have begun to test these theories empirically. This paper reviews both the theory and empirical evidence supporting and refuting the law and endowment views of property rights. The law view holds that historically determined differences in national legal traditions continue to shape cross-country differences in property rights. The endowment view argues that during European colonization, differences in climate, crops, the indigenous population, and the disease environment influenced long-run property rights.
Eight Questions about Corruption
Authors: Svensson Jakob
Published: October 2005

This paper will discuss eight frequently asked questions about public corruption: (1) What is corruption? (2) Which countries are the most corrupt? (3) What are the common characteristics of countries with high corruption? (4) What is the magnitude of corruption? (5) Do higher wages for bureaucrats reduce corruption? (6) Can competition reduce corruption?( 7) Why have there been so few (recent) successful attempts to fight corruption? (8) Does corruption adversely affect growth?
Policy Watch: Reform of the U.S. Postal Service
Authors: Geddes R. Richard
Published: October 2005

The author first reviews the current structure and regulation of the U.S. Postal Service. He then discusses the changing size and composition of the U.S. mail stream. Many other countries have already undertaken comprehensive postal reform, including both privatization and demonopolization, and the author discusses what lessons their experience can provide. He concludes by evaluating current reform proposals in the United States.
Affirmative Action and Its Mythology
Authors: Fryer Roland G , Loury Glenn C
Published: October 2005

For more than three decades, critics and supporters of affirmative action have fought for the moral high ground through ballot initiatives and lawsuits, in state legislatures, and in varied courts of public opinion. The goal of this paper is to show the clarifying power of economic reasoning to dispel some myths and misconceptions in the racial affirmative action debates. We enumerate seven commonly held (but mistaken) views one often encounters in the folklore about affirmative action (affirmative action may involve goals and timelines, but definitely not quotas, e.g.). Simple economic arguments reveal these seven views to be more myth than fact.
Adam Smith, Behavioral Economist
Authors: Ashraf Nava , Camerer Colin F , Loewenstein George
Published: October 2005

Adam Smith's psychological perspective in The Theory of Moral Sentiments is remarkably similar to “dual-process” frameworks advanced by psychologists, neuroscientists, and more recently by behavioral economists, based on behavioral data and detailed observations of brain functioning. It also anticipates a wide range of insights regarding phenomena such as loss aversion, willpower, and fairness that have been the focus of modern behavioral economics. This essay draws attention to some of these connections.