bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease
Authors: Verkleij‐Hagoort AC , Verlinde M , Ursem NTC , Lindemans J , Helbing WA , Ottenkamp J , Siebel FMH , Gittenberger‐de Groot AC , De Jonge R , Bartelings MM , Steegers EAP , Steegers‐Theunissen RPM 
Published: November 2006

Objective  To investigate the inter‐relation between mother and infant homocysteine, folate and vitamin B12 status and the risk of a child with congenital heart disease (CHD).Design  Case–control study.Setting  Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.Population  Participants were 149 case‐mothers and their children with CHD (n= 151) and 183 control‐mothers with their children (n= 175).Methods  Approximately 17 months after the index‐pregnancy maternal fasting, children’s random venous blood samples were drawn to measure plasma total homocysteine, serum and red blood cell (RBC) folate, and serum vitamin B12 concentrations. Data were compared between cases and controls using the Mann–Whitney U test. The biochemical parameters were dichotomised according to the cutoff value of the 10th percentile of vitamin concentrations and the 90th percentile of homocysteine concentrations based on control data. Risk estimates for the association between CHD and the biochemical parameters were estimated in a logistic regression model.Main outcome measures  Medians (minimum–maximum) and odds ratios (OR) (95% confidence intervals [CI]).Results  The OR (95% CI) of having a child with CHD was 2.9 (1.4–6.0) for maternal hyperhomocysteinaemia (>14.3 μmol/l). This finding is substantiated by a significant concentration‐dependent risk (Ptrend= 0.004). Hyperhomocysteinaemic case‐mothers showed significantly lower serum folate and vitamin B12 concentrations than normohomocysteinaemic case‐mothers. Serum and RBC folate concentrations were significantly higher in case‐children than that in control‐children.Conclusions  Maternal hyperhomocysteinaemia is associated with an increased risk of CHD, partially due to low folate and vitamin B12 status. The folate status of children warrants further investigation.
Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training
Authors: Thijssen Dick H. J. , Vos Joost B. , Verseyden Caroline , Van Zonneveld Anton Jan , Smits Paul , Sweep Fred C. G. J. , Hopman Maria T. E. , De Boer Hetty C. 
Published: November 2006

SummaryThe number of hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is thought to be a marker for neovascularization and vascular repair. Because physical inactivity and aging are risk factors for cardiovascular diseases, these factors may influence the numbers of HSCs and EPCs. Therefore, we examined baseline and exercise‐induced levels of HSCs and EPCs in sedentary and trained young and older men. To study the role of aging in eight sedentary young (19–28 years) and eight sedentary older men (67–76 years), baseline and acute exercise‐induced numbers of HSCs (CD34+‐cells) and EPCs (CD34+/VEGFR‐2+‐cells) were quantified by fluorescence‐activated cell sorter (FACS) analysis. To examine the effect of chronic training, eight age‐matched trained young men (18–28 years) were compared with sedentary young men, whereas older men performed an 8‐week endurance training. Older men showed significantly lower baseline and exercise‐induced levels of HSCs/EPCs than the young men (P < 0.05). In young and older men, acute exercise significantly increased HSCs (P < 0.01), but not EPCs. The absolute increase in numbers of HSCs was attenuated in older men (P = 0.03). Apart from the lower baseline numbers of EPCs after chronic training in older men, training status did not alter baseline or exercise‐induced levels of HSCs/EPCs in young and older men. We concluded that advancing age results in lower circulating numbers of HSCs and EPCs and attenuates the acute exercise‐induced increase in HSCs. Interestingly, in young as well as in older men chronic endurance training does not affect baseline and exercise‐induced numbers of HSCs and EPCs.
SECONDARY MORTGAGE MARKET PURCHASE COMMITMENT YIELDS
Authors: Heuson Andrea J. , Schwartz Adam , Slawson V. Carlos 
Published: November 2006

AbstractWe provide empirical evidence that quoted secondary market mortgage yields conform to the predictions of option theory. We compare Fannie Mae and Freddie Mac origination yields offered in the secondary market from 1985 to 2003 with the predictions of a two‐state binomial mortgage option valuation model. Our two‐state approach considers a mean‐reverting interest rate process as well as a stochastic housing price. Using predictions from option simulations, we find strong links between market practice and mortgage option prepayment and default factors over time. We also find cross‐sectional differences that are consistent with the institutional structure of the markets.
PRESIDENTIAL ELECTION UNCERTAINTY AND COMMON STOCK RETURNS IN THE UNITED STATES
Authors: Li Jinliang , Born Jeffery A. 
Published: November 2006

AbstractThere is substantial evidence on the influence of political outcomes on the business cycle and stock market. We further hypothesize that uncertainty about the outcome of a U.S. presidential election should be reflected in pre‐election common stock returns. Prior research pools returns based on the party of the winning candidate, assuming that the outcome of the election is known a priori. We use candidate preference (i.e., polling) data to construct a measure of election uncertainty. We find that if the election does not have a candidate with a dominant lead, stock market volatility (risk) and average returns rise.
Judicial Beginnings: The Supreme Court in the 1790s
Authors: Frankel Robert P. 
Published: November 2006

AbstractThere has long been a tendency to mark the beginning of the Supreme Court's history with the appointment of John Marshall as chief justice in 1801. But as the volumes of The Documentary History of the Supreme Court of the United States, 1789–1800 have exhibited, the first decade of the Court's life deserves significant attention. In the 1790s the Court asserted its autonomy, played an important role in setting the federal‐state balance, and, prior to Marbury v. Madison, exercised the authority of judicial review. The justices who sat on the Court in its first decade essentially shared the views of the two presidents who appointed them, George Washington and John Adams, but made it clear that the judiciary did not exist to serve either the executive or the legislature.
Quantitative Analysis of Representative Proteome Components and Clustering of Helicobacter pylori Clinical Strains
Authors: Park Jeong‐Won , Song Jae‐Young , Lee Seung‐Gyu , Jun Jin‐Su , Park Jeong‐Uck , Chung Mi‐Ja , Ju Jung‐Soo , Nizamutdinov Damir , Chang Myung‐Woong , Youn Hee‐Shang , Kang Hyung‐Lyun , Baik Seung‐Chul , Lee Woo‐Kon , Cho Myung‐Je , Rhee Kwang‐Ho 
Published: November 2006

AbstractBackground:  Several Helicobacter pylori proteins have been reported to be associated with severe symptoms of gastric disease. However, expression levels of most of these disease‐associated proteins require further evaluation in order to clarify their relationships with gastric disease patterns. Representative proteome components of 71 clinical isolates of H. pylori were analyzed quantitatively to determine whether the protein expression levels were associated with gastric diseases and to cluster clinical isolates.Methods:  After two‐dimensional electrophoresis (2‐DE) of H. pylori isolates, spot intensities were analyzed using pdquest 2‐D Gel Analysis Software. The intensities of 10 representative protein spots, identified by peptide fingerprinting using matrix assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF‐MS) or peptide sequencing using quadrupole TOF MS, were subjected to the nonparametric Mann–Whitney test and hierarchical agglomerative cluster analysis. The relationship between clusters and gastric diseases was analyzed by the chi‐squared test.Results:  Although the spot intensities of the 10 representative proteins were highly variable within each gastric disease group, the expression levels of CagA, UreB, GroEL, EF‐Tu, EF‐P, TagD, and FldA showed some significant differences among the gastric disease patterns. On the basis of the 10 target protein intensities, hierarchical agglomerative cluster analysis generated a dendrogram with clusters indicative of chronic gastritis/gastric cancers and gastric/duodenal ulcers.Conclusion:  These results indicated that quantitative analysis of proteome components is a feasible method for examining disease‐associated proteins and clustering clinical strains of H. pylori.
2‐Week Triple Therapy for Helicobacter pylori Infection is Better Than 1‐Week in Clinical Practice: a Large Prospective Single‐Center Randomized Study
Authors: Paoluzi Paolo , Iacopini Federico , Crispino Pietro , Nardi Francesco , Bella Antonino , Rivera Margherita , Rossi Pina , Gurnari Maurizio , Caracciolo Francesco , Zippi Maddalena , Pica Roberta 
Published: November 2006

AbstractBackground:  Proton pump inhibitor (PPI)‐based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. The aim of this study was to compare the efficacy of 1‐week versus 2‐week triple therapies in H. pylori‐positive patients.Materials and Methods:  A total of 486 consecutive H. pylori‐positive patients were randomized to receive omeprazole, 20 mg b.i.d., clarithromycin 500 mg b.i.d., and either amoxicillin 1 g b.i.d. or metronidazole 500 mg b.i.d. for 1 or 2 weeks. Upper gastrointestinal endoscopy and histology were performed at entry and 2 months after the end of therapy. H. pylori status was defined according to histology and urea breath test.Results:  At intention‐to‐treat analysis, 2‐week therapy with omeprazole, amoxicillin, and clarithromycin achieved a significantly higher eradication rate than 1‐ or 2‐week regimens with metronidazole (70% versus 52%, p = .003, versus 56%, p < .01) and the same therapy for 1‐week (70% versus 57%, p = .05). At per‐protocol analysis, 2‐week therapy with omeprazole, amoxicillin, and clarithromycin showed a significantly higher eradication rate than 1‐week of amoxicillin and metronidazole (77% versus 62%; p = .03) but no difference with 1‐week same regimen (66%) or 2‐week metronidazole and clarithromycin regimen (72%). Compliance and tolerability were good for all regimens.Conclusions:  Two‐week therapies, independently of antibiotic combination, lead to a significant increase of H. pylori eradication rate compared to 1‐week therapies, with same compliance and tolerability, even if, taking account of low‐eradication rates, one must question whether the triple therapy should still be used.
The Electroanatomic Characteristics of the Cavotricuspid Isthmus: Implications for the Catheter Ablation of Atrial Flutter
Authors: CHANG SHIH‐LIN , TAI CHING‐TAI , LIN YENN‐JIANG , ONG MARY GERTRUDE , WONGCHAROEN WANWARANG , LO LI‐WEI , CHANG SHENG‐HSIUNG , HSIEH MING‐HSIUNG , CHEN SHIH‐ANN 
Published: November 2006

Introduction: Radiofrequency ablation (RFA) of typical AFL is sometimes difficult because of the poor electroanatomic approach to the cavotricuspid isthmus (CTI). The aim of this study was to correlate the anatomy of the CTI between contact mapping (NavX) and right atrial angiography (RAG), and to investigate the impact of the electroanatomic characteristics of the CTI on the RFA of typical atrial flutter (AFL). Methods: One hundred patients with typical AFL undergoing RFA were studied. The image‐guided group consisted of 50 consecutive patients with the guidance of NavX. NavX geometry and RAG were performed to investigate the morphology of the CTI. The bipolar voltages of the CTI were collected during sinus rhythm by a NavX. The control group consisted of 50 consecutive patients with the guidance of conventional fluoroscopy. Results: There was a good correlation between the angiography and NavX for the anatomy of the CTI. The pouch type had a longer length of CTI than the flat type (33.4 ± 5.0 vs 22.6 ± 8.4 mm, P < 0.0001) and deeper depth than the concave type (6.5 ± 2.2 vs 3.7 ± 0.8 mm, P < 0.0001) on the angiography. The pouch‐type CTI had a longer ablation time and larger pulses of RFA than the other two types. The control group had a longer ablation time, fluoroscopy time, and larger pulses of RFA than image‐guided group. Conclusions: The 3‐D mapping system provided a good reconstruction of CTI, which may help in the RFA in patients with a complex anatomy of the CTI.
Species-Specific Differences in the Activity of PrfA,the Key Regulator of Listerial VirulenceGenes
Authors: Mauder Norman , Ecke Regina , Mertins Sonja , Loeffler Daniela I. M. , Seidel Gerald , Sprehe Mareen , Hillen Wolfgang , Goebel Werner , Müller-Altrock Stefanie 
Published: November 2006

ABSTRACTPrfA, the master regulator of LIPI-1, is indispensable for the pathogenesis of the human pathogenListeria monocytogenesand the animal pathogenListeria ivanovii. PrfA is also present in the apathogenic speciesListeria seeligeri, and in this study, we elucidate the differences between PrfA proteins from the pathogenic and apathogenic species of the genusListeria. PrfA proteins ofL. monocytogenes(PrfALmand PrfA*Lm),L. ivanovii(PrfALi), andL. seeligeri(PrfALs) were purified, and their equilibrium constants for binding to the PrfA box of thehlypromoter (PhlyLm) were determined by surface plasmon resonance. In addition, the capacities of these PrfA proteins to bind to the PrfA-dependent promoters Phlyand PactAand to form ternary complexes together with RNA polymerase were analyzed in electrophoretic mobility shift assays, and their abilities to initiate transcription in vitro starting at these promoters were compared. The results show that PrfALiresembled the constitutively active mutant PrfA*Lmmore than the wild-type PrfALm, whereas PrfALsshowed a drastically reduced capacity to bind to the PrfA-dependent promoters Phlyand PactA. In contrast, the efficiencies of PrfALm, PrfA*Lm, and PrfALiforming ternary complexes and initiating transcription at Phlyand PactAwere rather similar, while those of PrfALswere also much lower. The low binding and transcriptional activation capacities of PrfALsseem to be in part due to amino acid exchanges in its C-terminal domain (compared to PrfALmand PrfALi). In contrast to the significant differences in the biochemical properties of PrfALm, PrfALi, and PrfALs, the PrfA-dependent promoters ofhly(PhlyLm, PhlyLi, and PhlyLs) andactA(PactALm, PactALi, and PactALs) of the threeListeriaspecies did not significantly differ in their binding affinities to the various PrfA proteins and in their strengths to promote transcription in vitro. The allelic replacement ofprfALmwithprfALsinL. monocytogenesleads to low expression of PrfA-dependent genes and to reduced in vivo virulence ofL. monocytogenes, suggesting that the altered properties of PrfALsprotein are a major cause for the low virulence ofL. seeligeri.
Salmonella enterica
Serovar Typhimurium Periplasmic Superoxide Dismutase SodCI Is a Member of the PhoPQ Regulon and Is Induced in Macrophages
Authors: Golubeva Yekaterina A. , Slauch James M. 
Published: November 2006

ABSTRACT

Salmonella enterica
serovar Typhimurium replicates within host macrophages during the systemic stage of infection. In the macrophage, the bacteria must survive the respiratory burst that produces superoxide. Serovar Typhimurium strain 14028 produces two periplasmic superoxide dismutases, SodCI and SodCII, but only SodCI contributes to virulence. Although we have shown that this is primarily due to differences in the two proteins, evidence suggests differential regulation of the two genes. Using transcriptional
sodCI-
and
sodCII-lac
fusions, we show that
sodCII
is under the control of the RpoS sigma factor, as was known for the
Escherichia coli
ortholog,
sodC
. In contrast, we show that
sodCI
is transcriptionally controlled by the PhoPQ two-component regulatory system, which regulates an array of virulence genes required for macrophage survival. Introduction of a
phoP
-null mutation into the
sodCI
fusion strain resulted in a decrease in transcription and loss of regulation. The
sodCI
-
lac
fusion showed high-level expression in a background containing a
phoQ
constitutive allele. The
sodCI
gene is induced 15-fold in bacteria recovered from either the tissue culture macrophages or the spleens of infected mice. Induction in macrophages is dependent on PhoP. The
sodCII
fusion was induced three- to fourfold in macrophages and animals; this induction was unaffected by loss of PhoP. Thus,
sodCI
, which is horizontally transferred by the Gifsy-2 phage, is regulated by PhoPQ such that it is induced at the appropriate time and place to combat phagocytic superoxide.
The Ser/Thr Protein Kinase PknB Is Essential for Sustaining Mycobacterial Growth
Authors: Fernandez Pablo , Saint-Joanis Brigitte , Barilone Nathalie , Jackson Mary , Gicquel Brigitte , Cole Stewart T. , Alzari Pedro M. 
Published: November 2006

ABSTRACT

The receptor-like protein kinase PknB from
Mycobacterium tuberculosis
is encoded by the distal gene in a highly conserved operon, present in all actinobacteria, that may control cell shape and cell division. Genes coding for a PknB-like protein kinase are also found in many more distantly related gram-positive bacteria. Here, we report that the
pknB
gene can be disrupted by allelic replacement in
M. tuberculosis
and the saprophyte
Mycobacterium smegmatis
only in the presence of a second functional copy of the gene. We also demonstrate that eukaryotic Ser/Thr protein kinase inhibitors, which inactivate PknB in vitro with a 50% inhibitory concentration in the submicromolar range, are able to kill
M. tuberculosis
H37Rv,
M. smegmatis
mc
2
155, and
Mycobacterium aurum
A+ with MICs in the micromolar range. Furthermore, significantly higher concentrations of these compounds are required to inhibit growth of
M. smegmatis
strains overexpressing PknB, suggesting that this protein kinase is the molecular target. These findings demonstrate that the Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth and support the development of protein kinase inhibitors as new potential antituberculosis drugs.
Distinct Roles for IFN Regulatory Factor (IRF)-3 and IRF-7 in the Activation of Antitumor Properties of Human Macrophages
Authors: Romieu-Mourez Raphaëlle , Solis Mayra , Nardin Alessandra , Goubau Delphine , Baron-Bodo Véronique , Lin Rongtuan , Massie Bernard , Salcedo Margarita , Hiscott John 
Published: November 2006

AbstractWhen properly activated, macrophages can be tumoricidal, thus making them attractive additions to standard cancer therapies. To this end, tolerance and activity of human autologous IFN-γ-activated macrophages, produced in large scale for clinical use (MAK cells), have been assessed in pilot trials in cancer patients. In the present study, we tested the hypothesis that activation of IFN regulatory factor (IRF)-3 and IRF-7, with subsequent type I IFN production, may be involved in the acquisition of new antitumor functions by macrophages. Adenoviral vectors were generated for the delivery of constitutively active forms of IRF-3 (Ad-IRF-3) or IRF-7 (Ad-IRF-7) into primary human macrophages. Cell death was observed in Ad-IRF-3-transduced macrophages, whereas Ad-IRF-7-transduced macrophages produced type I IFNs and displayed increased expression of genes encoding tumor necrosis factor (TNF)–related apoptosis-inducing ligand, interleukin (IL)-12, IL-15, and CD80, persisting for at least 96 hours. Expression of iNOS, TNF-α, FasL, IL-1, and IL-6 genes was unaltered by Ad-IRF-7 transduction. Interestingly, Ad-IRF-3 or Ad-IRF-7 transduction negatively regulated the transcription of protumorigenic genes encoding vascular endothelial growth factor and matrix metalloproteinase-2. Furthermore, Ad-IRF-7-transduced macrophages exerted a cytostatic activity on different cancer cell lines, including SK-BR-3, MCF-7, and COLO-205; the latter cells were shown previously to be insensitive to MAK cells. In conclusion, transduction of active forms of IRF-3 or IRF-7 differentially modulate the apoptotic and antitumor properties of primary macrophages, with active IRF-7 leading to the acquisition of novel antitumor effector functions. (Cancer Res 2006; 66(21): 10576-85)
Transgenic Mouse Model for Rapid Pharmacodynamic Evaluation of Antiandrogens
Authors: Ellwood-Yen Katharine , Wongvipat John , Sawyers Charles 
Published: November 2006

Abstract
Persistent androgen receptor signaling has been implicated as a critical factor in prostate cancer progression even at the hormone-refractory stage and provides strong rationale for developing novel androgen receptor antagonists. Traditional models for in vivo evaluation of antiandrogens are cumbersome because they rely on physiologic end points, such as the size of androgen-dependent tissues. Here, we describe a transgenic mouse (ARR2 Pb-Lux) that expresses luciferase specifically in the prostate in an androgen-dependent fashion. This signal is reduced by castration or by treatment with bicalutamide and can be quantified through noninvasive bioluminescent imaging. ARR2 Pb-Lux mice provide a novel method for rapid pharmacodynamic evaluation of novel pharmacologic compounds designed to inhibit androgen receptor signaling. (Cancer Res 2006; 66(21): 10513-6)
A Conserved RAS/Mitogen-Activated Protein Kinase Pathway Regulates DNA Damage–Induced Cell Death Postirradiation in Radelegans
Authors: Weidhaas Joanne B. , Eisenmann David M. , Holub Justin M. , Nallur Sunitha V. 
Published: November 2006

Abstract
Although the epidermal growth factor receptor (EGFR) signaling pathway is overactive in more than half of human cancers and mediates resistance to cytotoxic therapy, the molecular mechanisms of EGFR pathway–mediated resistance have remained elusive in cancer research. This difficulty partly stems from the lack of tissue models enabling clear separation of the many forms of cell death that the downstream signaling pathways of EGFR affect. We have created a model in Caenorhabditis elegans of radiation-induced reproductive cell death (“Radelegans”) in isolation of all other forms of cell death. We have employed Radelegans to genetically define the role of the EGFR signaling pathway in protection from reproductive cell death, the primary form of tumor stem or clonogen cell death postirradiation. We have found that the RAS/mitogen-activated protein kinase (MAPK) downstream signal transduction pathway of EGFR is critical for protection from reproductive cell death in Radelegans. In addition, we have shown that RAS/MAPK pathway signaling is genetically linear with the DNA damage response pathway and acts downstream of the DNA damage checkpoint in the radioresponse, implicating this pathway in DNA repair post-cytotoxic therapy. These findings support the hypothesis that enhanced repair is a mechanism of RAS/MAPK pathway–mediated resistance to cytotoxic therapy through its interaction with the DNA damage response pathway postirradiation. We postulate that these findings also help explain why current treatment strategies, based on the presumption that tumors have ineffective repair compared with normal tissues, are ineffective in EGFR/RAS/MAPK pathway–mediated tumors. Radelegans is a platform to further define the genetic basis of the radiation response in tissues. (Cancer Res 2006; 66(21): 10434-8)