bluuebunny/crossref_metadata_2025 huggingface dataset:
NUMERICAL SIMULATION OF QUASI-NORMAL MODES IN TIME-DEPENDENT BACKGROUND
Authors: XUE LI-HUI , SHEN ZAI-XIONG , WANG BIN , SU RU-KENG
Published: January 2004

We study the massless scalar wave propagation in the time-dependent Schwarzschild black hole background. We find that the Kruskal coordinate is an appropriate framework to investigate the time-dependent spacetime. A time-dependent scattering potential is derived by considering dynamical black hole with parameters changing with time. It is shown that in the quasinormal ringing both the decay time-scale and oscillation are modified in the time-dependent background.
NUCLEAR DOUBLE-BETA DECAY AND NEUTRINO MASSES
Authors: STOICA S.
Published: January 2004

The double-beta decay process has been widely investigated in the last two decades due to the possible lepton number nonconservation decay modes that may occur. An experimental evidence of these modes would lead to the conclusion that neutrino is a massive Majorana particle. At present, when the nonzero neutrino mass is convincingly proved by neutrino oscillation experiments, the double-beta decay investigations are the most promising for determining the absolute value of the neutrino mass. In this paper we give a brief review of some recent nuclear double-beta decay investigations in connection with neutrino mass. We discuss the potential of this process to search for beyond standard model physics, the QRPA-based methods for computing the relevant nuclear matrix elements and the derivation of neutrino masses both from double-beta decay and neutrino oscillation data and in agreement with the present cosmological constraints.
HIGHER ORDER MEASURES, GENERALIZED QUANTUM MECHANICS AND HOPF ALGEBRAS
Authors: CHRYSSOMALAKOS C. , ĐURĐEVICH MICHO
Published: January 2004

We study Sorkin's proposal of a generalization of quantum mechanics and find that the theories proposed derive their probabilities from k th order polynomials in additive measures, in the same way that quantum mechanics uses a probability bilinear in the quantum amplitude and its complex conjugate. Two complementary approaches are presented, a C* and a Hopf-algebraic one, illuminating both algebraic and geometric aspects of the problem.
THE PHOTON SPECTRUM IN ORTHOPOSITRONIUM DECAY AT ωγ ≪ me
Authors: VOLOSHIN M. B.
Published: January 2004

A closed analytic expression is given for the spectrum of low energy photons in the annihilation of orthopositronium, which expression sums all the effects of the Coulomb interaction between the electron and the positron. The applicability of the formula is limited only by the condition ωγ ≪ me. In the region ωγ ≫ meα2 the Coulomb interaction term gives the leading at low energy one-loop correction, proportional to [Formula: see text], to the decay spectrum. The constant in ωγ radiative term in the one-loop correction to the spectrum is also presented here in an analytic form.
ENTANGLEMENT-ASSISTED CLASSICAL INFORMATION CAPACITY OF THE AMPLITUDE DAMPING CHANNEL
Authors: LIANG XIAN-TING
Published: January 2004

In this paper, we calculate the entanglement-assisted classical information capacity of the amplitude damping channel and compare it with the particular mutual information which is considered as the entanglement-assisted classical information capacity of this channel in Ref. 6. It is shown that the difference between them is very small. In addition, we point out that using partial symmetry and concavity of mutual information derived from the dense coding scheme, one can simplify the calculation of entanglement-assisted classical information capacities for non-unitary-covariant quantum noisy channels.
Determinants of Derivative Usage in the Life and General Insurance Industry: The Australian Evidence
Authors: De Ceuster Marc , Flanagan Liam , Hodgson Allan , Tahir Mohammad I.
Published: January 2004

Core business and financial market risks are not easily reduced by standard operating procedures in insurance companies. Derivatives theoretically provide a cost effective vehicle to hedge these risks. This paper provides an empirical analysis of the determinants of derivative usage as well as the extent of derivative usage in the Australian insurance industry in both life and general insurance companies for the period 1997–1999.

Empirical results for the Australian life insurance industry in general confirm the findings of UK and US based research. However, the Australian general insurance industry does not appear to follow the conclusions of previous literature. Our results indicate that for life insurers, the determinants of derivative usage were size, leverage and reinsurance. For the general insurance industry the determinants were size and the extent of long tail lines of business written. As regards the determinants of the extent of derivative usage, these were size and asset-liability duration mismatches for life insurers. For the general insurance industry the determinants of the extent of derivative usage were size, the extent of long tail lines of business written, and the reporting year.
The Determinants of Derivatives Use: Evidence from Non-Financial Firms in Taiwan
Authors: Shu Pei-Gi , Chen Hsuan-Chi
Published: January 2004

This paper examines the major determinants of a firm's derivatives use for companies listed in Taiwan Stock Exchange in the period from 1997 to 1999. The study finds that the proportion of derivatives use in Taiwan, ranging from 31% to 37%, is comparable to that of the US (35%), but less than that of New Zealand (53%). Firms' derivatives use in Taiwan asymmetrically focuses on currency/forwards derivatives. Industry breakdown illustrates that the electronic industry stands for the heavy user both in terms of number and amount. We show that the vital determinants of a firm's derivatives use are size, the ratio of long-term debt to total debt, the electronic industry dummy, and the export ratio. The fact that firms' derivatives use positively correlated with size and the long-term-debt-to-total-debt ratio implies the capability-willingness hypothesis: only large firms are affordable to engage in derivatives use due to the concern of economies of scale in establishing and maintaining expertise, and these firms demand more derivatives use when they face with high financial risk in debt structure.
AUTOMATIC THRESHOLDING FOR CORRESPONDENCE DETECTION
Authors: KANATANI KENICHI , KANAZAWA YASUSHI
Published: January 2004

We study the problem of thresholding the residual of template matching as a preprocess for selecting the correct matches between feature points in two images. In order to determine the threshold dynamically, we introduce a statistical model of the residual and compute an optimal threshold according to that model. The model parameters are estimated from the histogram of the residuals of candidate matches. Using real images, we show that our method can substantially upgrade the quality of the initial matches by simply adjusting the threshold.
AUTOMATIC DETECTION OF CIRCULAR OBJECTS BY ELLIPSE GROWING
Authors: KANATANI KENICHI , OHTA NAOYA
Published: January 2004

We present a new method for the automatic detection of circular objects in images: we detect an osculating circle to an elliptic arc using a Hough transform, iteratively deforming it into an ellipse, removing outlier pixels, and searching for a separate edge. The voting space for the Hough transform is restricted to one and two dimensions for efficiency, and special weighting schemes are introduced to enhance the accuracy. We demonstrate the effectiveness of our method using real images. Finally, we apply our method to the calibration of a turntable for 3D object shape reconstruction.
AUTOMATED SPLINE SURFACE MODELING AND MATCHING FOR RECOGNITION OF FREE-FORM OBJECTS
Authors: MAMIC G. , BENNAMOUN M.
Published: January 2004

Surface representations are utilized in a multitude of applications such as computer vision, medical imaging and computer graphics. B-spline surfaces have a number of desirable properties for representing surfaces, however, the complexity of knot placement strategies has prevented their widespread use in high-level vision environments. A solution to this problem is formulated within the reversible jump Markov chain Monte Carlo framework, whereby a derived posterior distribution may be sampled to calculate expected values for the number of knots required, their expected positions and a maximum likelihood estimate for the resulting control net of a given surface. Recognition of individual models may then be achieved using a hash table constructed using the principal components of the model control nets. Results of the fitting procedure, in terms of estimated knot vectors and spline surface errors, and the recognition of objects are provided for a set of free-form objects.
MULTIPLE LOOK ANGLE SAR RECOGNITION
Authors: BHANU BIR , JONES GRINNELL
Published: January 2004

The focus of this paper is optimizing the recognition of vehicles in Synthetic Aperture Radar (SAR) imagery by exploiting the azimuthal variance of scatterers using multiple SAR recognizers at different look angles. The variance of SAR scattering center locations with target azimuth leads to recognition system results at different azimuths that are independent, even for small azimuth deltas. Extensive experimental recognition results are presented in terms of receiver operating characteristic (ROC) curves to show the effects of multiple look angles on recognition performance for MSTAR vehicle targets with configuration variants, articulation, and occlusion.
PRINCIPLE OF THE CURRENT-VOLTAGE DUALITY IN THE CIRCUIT THEORY OF THE NEAR-EQUILIBRIUM NOISE
Authors: GRAFOV B. M.
Published: January 2004

This paper describes the application of the general principle of the current-voltage duality to the two-terminal distributed non-linear system in order to analyze its near-equilibrium internal noise. It is shown that an excess of the near-equilibrium noise with respect to the Nyquist level is proportional to the small-signal rectification magnitude.
Steroid 5α-Reductase 1 Polymorphisms and Testosterone/Dihydrotestosterone Ratio in Male Patients with Hypospadias
Authors: Tria Antje , Hiort Olaf , Sinnecker Gernot H.G.
Published: January 2004

Background/Aim: Defects in the steroid 5α-reductase type 2 (SRD5A2) activity cause decreased formation of dihydrotestosterone (DHT) from testosterone (T), resulting in defective masculinization of external genitalia; the T/DHT ratio is increased. We investigated 10 patients with elevated T/DHT ratios in whom mutations in the SRD5A2 and AR genes had been excluded to find out whether structural alterations of the SRD5A1 gene could contribute to their genital malformations. Methods: Single-strand conformation polymorphism analysis and direct sequencing were used to detect variations in the SRD5A1 gene of the patients and of 49 adult fertile men who served as controls. Results: The sequence analysis of exon 3 of the SRD5A1 gene indicated an adenine-to-guanine change (ACA vs. ACG), both triplets encoding the amino acid residue threonine. The ACG sequence was detected in 57% of all subjects and was equally distributed in patients and controls. The T/DHT ratio was significantly higher in controls with the ACG variant as compared with those having the ACA variant. However, no particular sequence aberration was found in the SRD5A1 genes of either group. Conclusion: Mutant SRD5A1 isoenzyme does not seem to play a crucial role in the development of hypospadias.
Hematological Parameters and Cobalamin Status in Infants Born to Smoking Mothers
Authors: Bjørke Monsen Anne-Lise , Vollset Stein Emil , Refsum Helga , Markestad Trond , Ueland Per Magne
Published: January 2004

Hematological parameters, serum cobalamin and folate levels, and the concentrations of the functional markers plasma methylmalonic acid and total homocysteine were determined in 173 newborns and 46 infants at 6 weeks to see whether maternal smoking influences the hematological parameters and the vitamin status of the newborn. At birth, there was a strong inverse correlation between the number of cigarettes smoked per day during pregnancy and red blood cell count (r = –0.56, p = 0.001) and hemoglobin level (r = –0.52, p = 0.003) in the newborns. Neonates born to smoking mothers had lower red blood cell counts and lower hemoglobin and serum cobalamin levels as compared with infants born to nonsmoking mothers. At 6 weeks, maternal smoking significantly predicted the methylmalonic acid and total homocysteine levels, suggesting an influence from smoking on the cobalamin function in these infants.
Gender Determines Long-Lasting Effects on Adult Offspring Heart after Early-Life Malnourishment
Authors: Sanchez Moura Anibal , Gomes Pereira Flavia , Mandarim-de-Lacerda Carlos Alberto
Published: January 2004

This study evaluates the effect of insulin in the association between nutrition and gender during lactation on inducing changes in heart morphology of pups when adults. Two groups of lactating rat dams were fed a normal diet containing 22% protein or 0% protein during the first 10 days of lactation. Eight-day-old rats from the female control group (FC) displayed a heart weight/body weight (H/B) ratio 100% greater when compared with the male control group (MC). An increased H/B ratio (65%) was found in the MC group when compared with the male malnourished group (MM). An effect on the development was present in the FC group in which, at 8 days, the H/B ratio was 70% greater than in this group at 60 days of age. A similar effect was observed in the female malnourished group (FM), where the H/B ratio was 100% greater. The effect on the development, at 8 days, in the FC group, when compared with the females at 60 days, displayed a larger cardiomyocyte volume [QA(c)] and a higher cardiomyocyte density [Vv(c)]: QA[c] 220% greater (p < 0.05) and Vv[c] 530% greater (p < 0.01). The FM group, at 8 days of age, had the QA[c] and Vv[c] greater than at the age of 60 days: QA[c] 100% greater (p < 0.05) and Vv[c] 290% greater (p < 0.05). The insulin/glucose ratio reflected the variable gender associated with the malnourishment in the male animals at 8 days of age. In these animals the insulin/glucose ratio of the malnourished animals was found to be reduced by 42% when compared with the control groups. At 60 days of age, a difference in the insulin/glucose ratio was present between FC and FM groups (33% greater in the FC group, p < 0.05). Gender was associated with a high insulin/glucose ratio in MC and MM groups when compared with the FC and FM groups. Also this association was observed in the animals at 60 days of age when the insulin/glucose ratio of the MM animals was 45% greater than that observed in the FM group.
Ciprofloxacin Treatment in Newborns with Multi-Drug-Resistant Nosocomial PseudomonasInfections
Authors: Belet Nurşen , Haciömeroğlu Pelin , Küçüködük Şükrü
Published: January 2004

Objectives: To evaluate the efficacy and acute side effects of ciprofloxacin treatment in newborns who developed nosocomial Pseudomonas aeruginosa infection. Methods: Intravenous ciprofloxacin treatment was given to 30 newborns who developed nosocomial P. aeruginosa infection as proven by culture antibiogram results. Initial doses of 10 mg/kg/day were given and increased up to 40 mg/kg/day according to clinical response, laboratory and culture results. During therapy, complete white blood cell counts, urinalysis, liver and renal function tests were performed weekly. All patients were examined daily during treatment for possible symptoms of joint toxicity such as erythema and swelling. The patients were evaluated by general physical examination, with special attention to joints, 1 week after discharge. Results: Two of the patients (6.6%) died due to pseudomonas infection, but the bacteria were successfully eradicated in 28 patients (93.4%). Four patients died from other causes. No laboratory abnormality related to ciprofloxacin was observed during treatment. Swelling and hyperemia of the joints were not encountered during treatment and the 1-week period after discharge. Ciprofloxacin-resistant P. aeruginosa isolates were not grown during the study. Conclusion: Ciprofloxacin treatment is effective in life-threatening multi-drug-resistant P. aeruginosa infections.
The Link between Exposure to Dioxin and Endometriosis: A Critical Reappraisal of Primate Data
Authors: Guo Sun-Wei
Published: January 2004

Endometriosis is a common and enigmatic disease affecting women of reproductive age. In 1993, Dr. Sherry Rier and her colleagues reported a serendipitous finding that quickly sent a shock wave through the endometriosis research community. They found that rhesus monkeys exposed daily for 4 years to dioxin developed endometriosis, with incidence and severity related to dose. The study prompted more animal and epidemiologic studies regarding the link between dioxin exposure and endometriosis. Yet, 10 years after the first piece of evidence was reported, the primate data are still equivocal, and the human data supporting the dioxin-endometriosis association are scanty and conflicting. While many reviewers of the subject recognize the need for more data, other reviewers tend to discount negative studies when reviewing positive studies. In this paper, a critical reappraisal of all evidence from human and primate data is presented. While there is evidence suggesting that exposure to dioxin may facilitate the short-term survival of endometrial implants in non-human primates, this evidence is not supported by both human and non-human primate studies evaluating the relationship between dioxin exposure and the development of spontaneous endometriosis. Weighing all converging evidence, it seems that there are no solid, credible data available at this moment to support the hypothesis that dioxin exposure may lead to the development of endometriosis.
Angiopoietin 2 Induces Cell Cycle Arrest in Endothelial Cells: A Possible Mechanism Involved in Advanced Plaque Neovascularization
Authors: Calvi Cristina , Dentelli Patrizia , Pagano Marco , Rosso Arturo , Pegoraro Marco , Giunti Sara , Garbarino Giovanni , Camussi Giovanni , Pegoraro Luigi , Brizzi Maria Felice
Published: January 2004

Objective—

To characterize the molecules and the mechanisms regulating the neoangiogenetic process in advanced atherosclerotic plaques.

Methods and Results—

Western blot and immunofluorescence analysis of atherosclerotic specimens demonstrated that unlike neovessels from early lesions that expressed vascular endothelial growth factor (VEGF) and angiopoietin1 (Angio1), vessels from advanced lesions expressed VEGF and angiopoietin 2 (Angio2). Moreover, only few neovessels from advanced lesions showed a positive immunostaining for proliferating cell nuclear antigen. Angio1-elicited and Angio2-elicited intracellular events in endothelial cells (EC) demonstrated that while Angio1 triggered Erk1/Erk2 mitogen activated protein kinases (MAPK) and Akt activation, Angio2 (50 ng/mL) induced STAT5 activation and p21
waf
expression and increased the fraction of cells in G1. Both Angio2-mediated events were abrogated by expressing a dominant negative STAT5 construct (ΔSTAT5). Consistent with the expression of Angio2 in neovessels of advanced lesions a transcriptionally active STAT5 was detected. Moreover, co-immunoprecipitation experiments revealed the presence of a STAT5/Tie2 molecular complex in neointima vessels from advanced, but not from early, lesions.

Conclusions—

In advanced lesions, the activation of the Tie2-mediated STAT5 signaling pathway may negatively regulate vessel growth.
Graft-Extrinsic Cells Predominate in Vein Graft Arterialization
Authors: Zhang Lisheng , Freedman Neil J. , Brian Leigh , Peppel Karsten
Published: January 2004

Objective—

Vein graft disease involves neointimal smooth muscle cells, the origins of which are unclear. This study sought to characterize and quantitate vein graft infiltration by cells extrinsic to the graft in a mouse model of vein graft disease.

Methods and Results—

Inferior vena cava-to-carotid artery interposition grafting between C57Bl/6 and congenic β-galactosidase–expressing ROSA26 mice was performed. Vein grafts were harvested 6 weeks postoperatively and stained with X-gal. More than 60% of neointimal cells derived from the recipient, and 50% of these cells expressed smooth muscle α-actin. The distribution of donor and recipient-derived cells within this vein graft wall layer was distinctly focal, consistent with focal infiltration and expansion of progenitor cells. When bone marrow transplantation with congenic green fluorescent protein (GFP)-expressing cells was used in vein graft recipients 1 month before surgery, abundant GFP-expressing cells appeared in the media, but not the neointima, of mature grafts. Endothelial cells in mature grafts derived from graft-intrinsic and graft-extrinsic sources and were, in part, of bone marrow origin.

Conclusions—

Cells extrinsic to the graft, including bone marrow-derived cells, predominate during vein graft remodeling.
Verapamil Increases the Apolipoprotein-Mediated Release of Cellular Cholesterol by Induction of ABCA1 Expression Via Liver X Receptor-Independent Mechanism
Authors: Suzuki Shogo , Nishimaki-Mogami Tomoko , Tamehiro Norimasa , Inoue Kazuhide , Arakawa Reijiro , Abe-Dohmae Sumiko , Tanaka Arowu R. , Ueda Kazumitsu , Yokoyama Shinji
Published: January 2004

Objective—Release of cellular cholesterol and phospholipid mediated by helical apolipoprotein and ATP-binding cassette transporter (ABC) A1 is a major source of plasma HDL. We investigated the effect of calcium channel blockers on this reaction.

Methods and Results—Expression of ABCA1, apoA-I–mediated cellular lipid release, and HDL production were enhanced in cAMP analogue-treated RAW264 cells by verapamil, and similar effects were also observed with other calcium channel blockers. The verapamil treatment resulted in rapid increase in ABCA1 protein and its mRNA, but not the ABCG1 mRNA, another target gene product of the nuclear receptor liver X receptor (LXR). By using the cells transfected with a mouse ABCA1 promoter–luciferase construct (−1238 to +57bp), verapamil was shown to enhance the transcriptional activity. However, it did not increase transcription of LXR response element-driven luciferase vector.

Conclusions—The data demonstrated that verapamil increases ABCA1 expression through LXR-independent mechanism and thereby increases apoA-I–mediated cellular lipid release and production of HDL.
Clinical Significance of Small Dense Low-Density Lipoprotein Cholesterol Levels Determined by the Simple Precipitation Method
Authors: Hirano Tsutomu , Ito Yasuki , Koba Shinji , Toyoda Miwako , Ikejiri Ayako , Saegusa Haruhisa , Yamazaki Jun-ichi , Yoshino Gen
Published: January 2004

Objective—

Recently, we established a simple method for the quantification of small dense LDL cholesterol (C) using heparin-magnesium precipitation. The small dense LDL-C level was identical to cholesterol in the denser LDL fraction with a density of 1.044 to 1.063 g/mL. The aim of this study was to examine clinical significance of this precipitation method for small dense LDL-C.

Methods and Results—

Small dense LDL-C was measured by a direct homogenous LDL-C assay in the supernatant that remained after heparin-magnesium precipitation with density <1.044 lipoproteins. In 313 normolipidemic subjects, the mean value of small dense LDL-C was 31±13 mg/dL. In 462 healthy subjects, small dense LDL-C levels were positively correlated with serum triglyceride and LDL-C and were inversely correlated with high-density lipoprotein cholesterol (HDL-C). Combined hyperlipidemia showed the highest small dense LDL-C level among the various types of hyperlipidemia. Patients with type 2 diabetes had an increased small dense LDL-C level (55±17). Patients with coronary heart disease also had increased small dense LDL-C levels (53±30) irrespective of the presence of diabetes, whereas their LDL-C levels were comparable to those of normolipidemic controls (111±31 versus 104±22).

Conclusion—

These results suggest that measurement of small dense LDL-C by the present precipitation method is useful to evaluate atherogenic risk and may be applicable to routine clinical examination.
Human Evidence That the Cystatin C Gene Is Implicated in Focal Progression of Coronary Artery Disease
Authors: Eriksson Per , Deguchi Hiroyuki , Samnegård Ann , Lundman Pia , Boquist Susanna , Tornvall Per , Ericsson Carl-Göran , Bergstrand Lott , Hansson Lars-Olof , Ye Shu , Hamsten Anders
Published: January 2004

Objective—

Overexpression of elastolytic cysteine and aspartic proteases, known as cathepsins, is implicated in atherogenesis. The potential significance of imbalance in expression between cathepsins and their inhibitor cystatin C in cardiovascular disease has been highlighted by the demonstration of cystatin C deficiency in human atherosclerosis and abdominal aortic aneurysms.

Methods and Results—

We identified and characterized physiologically relevant polymorphisms in the promoter region of the cystatin C gene that influence cystatin C production and used these polymorphisms as a tool to examine the significance of cystatin C in coronary atherosclerosis in vivo in humans. Seven polymorphisms, all in strong-linkage disequilibrium, were identified in the cystatin C gene, of which 2 promoter polymorphisms (−82G/C and −78T/G) were functional in vitro in electromobility shift and transient transfection assays. Genotyping of 1105 individuals (237 survivors of a first myocardial infarction before age 60 and 2 independent groups comprising a total of 868 healthy individuals) revealed that the plasma cystatin C concentration was significantly lower in carriers of the mutant haplotype. Furthermore, the mutant haplotype was associated with a higher average number of stenoses per coronary artery segment in unselected postinfarction patients (N=237) undergoing routine coronary angiography.

Conclusions—

These results provide human evidence for an important role of cystatin C in coronary artery disease.
Constitutive Expression and Involvement of Cyclooxygenase-2 in Human Megakaryocytopoiesis
Authors: Tanaka Nobuhito , Sato Takahiro , Fujita Hiroshi , Morita Ikuo
Published: January 2004

Objective—

Cyclooxygenase-1 (COX-1), but not COX-2, is expressed in human platelets, and thromboxane A
2
(TXA
2
) produced via COX-1 induces platelet aggregation. The objectives of this study were to investigate the expression of COX-1 and COX-2 during platelet differentiation and to determine whether these enzymes are involved in the differentiation.

Methods and Results—

CD34
+
progenitor cells isolated from human cord blood were cultured with thrombopoietin and c-kit ligand. The cells differentiated into megakaryocytes (CD34
−
/CD41
+
) after 8 days of culture and into platelets (CD41
+
/prodium iodide
−
) after 14 days of culture. The CD34
+
cells expressed a trace of COX-1 gene and no COX-2 gene. On day 5, COX-2 gene expression was observed and continued throughout the remainder of the culture. COX-1 gene expression increased after 8 days of culture. The treatment of this liquid culture with indomethacin, a dual inhibitor of COX-1 and COX-2, and NS-398, a COX-2–specific inhibitor, suppressed megakaryocyte differentiation. In contrast, at a dose of 10
−7
M, mofezolac, which is a highly selective inhibitor of COX-1, did not affect differentiation. NS-398–induced suppression of megakaryocyte differentiation was partly abrogated by stable analogues of TXA
2
.

Conclusions—

We report here that COX-2 and COX-1 are constitutively expressed in megakaryocytes, and TXA
2
produced by COX-2 plays an important role in megakaryocytopoiesis.
Telomere Shortening in Human Coronary Artery Diseases
Authors: Ogami Masayuki , Ikura Yoshihiro , Ohsawa Masahiko , Matsuo Toshihiko , Kayo Soichiro , Yoshimi Noriko , Hai Eishu , Shirai Nobuyuki , Ehara Shoichi , Komatsu Ryushi , Naruko Takahiko , Ueda Makiko
Published: January 2004

Background—

Increased cell turnover in response to injury is considered to be important in the development of atherosclerotic plaques. Telomere shortening has been shown to be associated with cell turnover. We assessed the telomere length of human coronary endothelial cells to clarify whether there is a relationship between telomere shortening and coronary artery disease (CAD).

Methods and Results—

Coronary endothelial cells were obtained from 11 patients with CAD who underwent autopsy and 22 patients without CAD who underwent autopsy by scraping off the luminal surface of coronary arteries. DNA extracted from the endothelial cells were blotted and hybridized with telomere-specific oligonucleotide ([TTAGGG]
4
). The hybridization signal intensity, which represented telomeric DNA content, was standardized with centromeric DNA content (T/C ratio) to estimate telomere length. The T/C ratios were significantly smaller (
P
<0.0001) in CAD patients than in age-matched non-CAD patients (CAD patients, 0.462±0.135; non-CAD patients, 1.002±0.212). In 6 individual CAD patients, the T/C ratio at the atherosclerotic lesion was significantly smaller (
P
<0.05) than that at the non-atherosclerotic portion.

Conclusions—

These findings suggest that focal replicative senescence and telomere shortening of endothelial cells may play a critical role in coronary atherogenesis and CAD.
Acetylcysteine Reduces Plasma Homocysteine Concentration and Improves Pulse Pressure and Endothelial Function in Patients With End-Stage Renal Failure
Authors: Scholze Alexandra , Rinder Christiane , Beige Joachim , Riezler Reiner , Zidek Walter , Tepel Martin
Published: January 2004

Background—

Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure.

Methods and Results—

We investigated the metabolic and hemodynamic effects of intravenous administration of acetylcysteine, a thiol-containing antioxidant, during a hemodialysis session in a prospective, randomized, placebo-controlled crossover study in 20 patients with end-stage renal failure. Under control conditions, a hemodialysis session reduced plasma homocysteine concentration to 58±22% predialysis (mean±SD), whereas in the presence of acetylcysteine, the plasma homocysteine concentration was significantly more reduced to 12±7% predialysis (
P
<0.01). The reduction of plasma homocysteine concentration was significantly correlated with a reduction of pulse pressure. A 10% decrease in plasma homocysteine concentration was associated with a decrease of pulse pressure by 2.5 mm Hg. Analysis of the second derivative of photoplethysmogram waveform showed changes of arterial wave reflectance during hemodialysis in the presence of acetylcysteine, indicating improved endothelial function.

Conclusions—

Acetylcysteine-dependent increase of homocysteine removal during a hemodialysis session improves plasma homocysteine concentration, pulse pressure, and endothelial function in patients with end-stage renal failure.
Atrial Extracellular Matrix Remodeling and the Maintenance of Atrial Fibrillation
Authors: Xu Jun , Cui Guanggen , Esmailian Fardad , Plunkett Mark , Marelli Daniel , Ardehali Abbas , Odim Jonah , Laks Hillel , Sen Luyi
Published: January 2004

Background—

Remodeling occurs in both ventricle and atrium in dilated cardiomyopathy and heart failure. However, the alteration of atrial extracellular matrix components during remodeling and its effect on the electrical remodeling and atrial arrhythmia have never been explored.

Methods and Results—

Atrial tissue samples of 53 explanted hearts from patients with dilated cardiomyopathy and end-stage heart failure who underwent heart transplantation were examined. Nineteen patients had permanent atrial fibrillation (PmAF), 18 had persistent AF (PsAF), and 16 had no documented AF (NAF). Sixteen donor left atria (LA) were used as controls (CNs). Western Blot analysis revealed a selective downregulation of tissue inhibitor of metalloproteinase (TIMP)-2 in PmAF and PsAF groups compared with the NAF and CN groups and an upregulation of atrial metalloproteinase (MMP)-2 that was most pronounced in the PmAF group followed by the PsAF and NAF groups. Immunofluorescent staining revealed that in the LA, type I collagen volume fraction (CVF-I) increased significantly in the PmAF group followed by the PsAF and NAF groups compared with that in CN. LA CVF-I significantly correlated with LA dimension and TIMP-2 to MMP-2 ratio. In the PsAF group, CVF-I/CVF-III ratio was significantly correlated with AF duration and the frequency of AF recurrence.

Conclusions—

Atrial extracellular matrix remodeling manifested by the selective downregulation of TIMP-2 along with upregulation of MMP-2 and CVF-I in the atrium is associated with the development of sustained atrial fibrillation in patients with cardiomyopathy and heart failure.
Cytomegalovirus Infection Impairs the Nitric Oxide Synthase Pathway
Authors: Weis Michael , Kledal Thomas N. , Lin Ken Y. , Panchal Shyam N. , Gao S. Z. , Valantine Hannah A. , Mocarski Edward S. , Cooke John P.
Published: January 2004

Background—

We hypothesized that cytomegalovirus (CMV) may contribute to the vasculopathy observed in cardiac allograft recipients by impairing the endothelial nitric oxide synthase pathway. We focused on asymmetric dimethylarginine (ADMA, the endogenous inhibitor of nitric oxide synthase) as a potential mediator of the adverse vascular effect of CMV.

Methods and Results—

Heart transplant recipients manifested elevated plasma ADMA levels compared with healthy control subjects. Transplant patients with CMV DNA–positive leukocytes had higher plasma ADMA concentrations and more extensive transplant arteriopathy (TA). Human microvascular endothelial cells infected with the CMV isolates elaborated more ADMA. The increase in ADMA was temporally associated with a reduction in the activity of dimethylarginine dimethylaminohydrolase (DDAH, the enzyme that metabolizes ADMA). Infected cultures showed high levels of oxidative stress with enhanced endothelial production of superoxide anion.

Conclusions—

CMV infection in human heart transplant recipients is associated with higher ADMA elevation and more severe TA. CMV infection in endothelial cells increases oxidative stress, impairs DDAH activity, and increases ADMA elaboration. CMV infection may contribute to endothelial dysfunction and TA by dysregulation of the endothelial nitric oxide synthase pathway.
Elevated Troponin T Levels and Lesion Characteristics in Non–ST-Elevation Acute Coronary Syndromes
Authors: Okamatsu Kentaro , Takano Masamichi , Sakai Shunta , Ishibashi Fumiyuki , Uemura Ryota , Takano Teruo , Mizuno Kyoichi
Published: January 2004

Background—

Elevated troponin T levels in non–ST-elevation acute coronary syndromes (NSTE-ACS) have been shown to predict an adverse outcome. Furthermore, it has been reported that troponin T could help improve the effectiveness of such new antithrombotic drugs as platelet GPIIb/IIIa antagonists and low-molecular-weight heparins. We hypothesized that such elevated troponin T levels in NSTE-ACS indicate the presence of thrombus at culprit lesions, and this hypothesis was verified through the use of coronary angioscopy.

Methods and Results—

We studied 57 consecutive patients with NSTE-ACS who underwent preinterventional angioscopy. Before catheterization, we obtained blood samples to determine troponin positivity, and the patients were then classified as either troponin-positive or troponin-negative groups (diagnostic threshold, 0.1 ng/mL). Using angioscopy at the culprit lesions, we examined the presence of coronary thrombus, yellow plaque, and complex plaque. Moreover, we compared the preinterventional angiographic parameters (thrombus and complexity of the culprit lesion, and TIMI flow) between the two groups. Twenty-two patients were troponin-positive and 35 patients were troponin-negative. Univariate analyses indicated that the TIMI flow and the incidence of coronary thrombus detected with angioscopy correlate with the elevated troponin T levels. A multivariate logistic regression analysis showed the presence of coronary thrombus detected with angioscopy to be the only independent factor associated with elevated troponin T levels in patients with NSTE-ACS (odds ratio, 22.1; 95% CI, 2.59 to 188.42;
P
=0.0046).

Conclusions—

Using angioscopy, the elevated troponin T levels in NSTE-ACS were confirmed to be strongly associated with the presence of coronary thrombus.
Targeted Gene Delivery to Vascular Tissue In Vivo by Tropism-Modified Adeno-Associated Virus Vectors
Authors: White Stephen J. , Nicklin Stuart A. , Büning Hildegard , Brosnan M. Julia , Leike Kristen , Papadakis Emmanuel D. , Hallek Michael , Baker Andrew H.
Published: January 2004

Background—

Gene therapy offers an unprecedented opportunity to treat diverse pathologies. Adeno-associated virus (AAV) is a promising gene delivery vector for cardiovascular disease. However, AAV transduces the liver after systemic administration, reducing its usefulness for therapies targeted at other sites. Because vascular endothelial cells (ECs) are in contact with the bloodstream and are heterogeneous between organs, they represent an ideal target for site-specific delivery of biological agents.

Methods and Results—

We isolated human venous EC-targeting peptides by phage display and genetically incorporated them into AAV capsids after amino acid 587. Peptide-modified AAVs transduced venous (but not arterial) ECs in vitro, whereas hepatocyte transduction was significantly lower than with native AAV. Intravenous infusion of engineered AAVs into mice produced reduced vector accumulation in liver measured 1 hour and 28 days after injection and delayed blood clearance rates compared with native AAV. Peptide-modified AAVs produced enhanced uptake of virions in the vena cava with selective transgene expression. Retargeting was dose dependent, and coinfusion of either heparin or free competing peptides indicated that uptake was principally independent of native AAV tropism and mediated via the peptide.

Conclusions—

AAV tropism can be genetically engineered by use of phage display–derived peptides to generate vectors that are selective for the vasculature.
Endogenous Estrogen Deficiency Reduces Proliferation and Enhances Apoptosis-Related Death in Vascular Smooth Muscle Cells
Authors: Ling Shanhong , Dai Aozhi , Dilley Rodney J. , Jones Margaret , Simpson Evan , Komesaroff Paul A. , Sudhir Krishnankutty
Published: January 2004

Background—

Altered proliferation and death of vascular smooth muscle cells (VSMCs) are important mechanisms in vascular growth and remodeling. This study examined the effect of endogenous estrogens on VSMC proliferation.

Methods and Results—

An estrogen-deficient animal model, the aromatase-knockout (ArKO) mouse, was used. Primary cultures of VSMCs were established from aortas of 11-week-old male and female ArKO and wild-type (WT) mice. In ArKO cells, the absence of aromatase cytochrome P450 mRNA expression was demonstrated by reverse transcription–polymerase chain reaction; Western blotting showed normal expression of estrogen receptor protein. Proliferative responses to serum or platelet-derived growth factor-BB were lower in ArKO than WT cells; 17β-estradiol (E
2
, 10 nmol/L) enhanced the response to platelet-derived growth factor-BB in ArKO cells but inhibited the response in WT cells. E
2
inhibited activity of mitogen-activated protein kinase ERK1/2 in WT but not ArKO cells. Apoptosis-related death caused by tumor necrosis factor-α was greater in ArKO than in WT cells; this effect in ArKO was attenuated by E
2
. Differences in VSMC proliferation between ArKO and WT occurred in both sexes. Morphological studies in aortas derived from male mice at 1 year of age demonstrated that medial smooth muscle area was ≈10% less in ArKO than WT mice at this age.

Conclusions—

Deficiency of endogenous estrogens reduces proliferation and enhances apoptosis-related death in VSMCs; exogenous E
2
corrects these abnormalities.
Adrenomedullin Gene Transfer Induces Therapeutic Angiogenesis in a Rabbit Model of Chronic Hind Limb Ischemia
Authors: Tokunaga Noriyuki , Nagaya Noritoshi , Shirai Mikiyasu , Tanaka Etsuro , Ishibashi-Ueda Hatsue , Harada-Shiba Mariko , Kanda Munetake , Ito Takefumi , Shimizu Wataru , Tabata Yasuhiko , Uematsu Masaaki , Nishigami Kazuhiro , Sano Shunji , Kangawa Kenji , Mori Hidezo
Published: January 2004

Background—

Earlier studies have shown that adrenomedullin (AM), a potent vasodilator peptide, has a variety of cardiovascular effects. However, whether AM has angiogenic potential remains unknown. This study investigated whether AM gene transfer induces therapeutic angiogenesis in chronic hind limb ischemia.

Methods and Results—

Ischemia was induced in the hind limb of 21 Japanese White rabbits. Positively charged biodegradable gelatin was used to produce ionically linked DNA-gelatin complexes that could delay DNA degradation. Human AM DNA (naked AM group), AM DNA-gelatin complex (AM-gelatin group), or gelatin alone (control group) was injected into the ischemic thigh muscles. Four weeks after gene transfer, significant improvements in collateral formation and hind limb perfusion were observed in the naked AM group and AM-gelatin group compared with the control group (calf blood pressure ratio: 0.60±0.02, 0.72±0.03, 0.42±0.06, respectively). Interestingly, hind limb perfusion and capillary density of ischemic muscles were highest in the AM-gelatin group, which revealed the highest content of AM in the muscles among the three groups. As a result, necrosis of lower hind limb and thigh muscles was minimal in the AM-gelatin group.

Conclusions—

AM gene transfer induced therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia. Furthermore, the use of biodegradable gelatin as a nonviral vector augmented AM expression and thereby enhanced the therapeutic effects of AM gene transfer. Thus, gelatin-mediated AM gene transfer may be a new therapeutic strategy for the treatment of peripheral vascular diseases.
Prospective Analysis of Mannose-Binding Lectin Genotypes and Coronary Artery Disease in American Indians
Authors: Best Lyle G. , Davidson Michael , North Kari E. , MacCluer Jean W. , Zhang Ying , Lee Elisa T. , Howard Barbara V. , DeCroo Susan , Ferrell Robert E.
Published: January 2004

Background—

Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD.

Methods and Results—

We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2,
P
=0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0,
P
=0.004).

Conclusions—

Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.
Neuregulin-1 Induces a Negative Inotropic Effect in Cardiac Muscle
Authors: Lemmens Katrien , Fransen Paul , Sys Stanislas U. , Brutsaert Dirk L. , De Keulenaer Gilles W.
Published: January 2004

Background—

Deficient cardiac neuregulin/ErbB signaling increases susceptibility to heart failure. In this study, we examined the effects of neuregulin-1 (NRG-1) on myocardial contractility.

Methods and Results—

NRG-1 (α and β isoforms) induced a negative inotropic effect in isolated rabbit papillary muscles and a rightward shift of the dose-response curve to isoproterenol. Both effects were attenuated by L-NMMA, which suggests a role for NO synthase. In cultured rat cardiomyocytes, NRG-1β enhanced nitrite production and resulted in phosphorylation of endothelial NO synthase and the serine/threonine kinase Akt.

Conclusions—

NRG-1 has negative inotropic effects that are preserved during β-adrenergic stimulation and activates endothelial NO synthase in cardiomyocytes.
Alterations in Sympathetic Ganglionic Transmission in Response to Angiotensin II in (mRen2)27 Transgenic Rats
Authors: Aileru Azeez A. , Logan Exazevia , Callahan Michael , Ferrario Carlos M. , Ganten Detlev , Diz Debra I.
Published: January 2004

Hypertension in (mRen2)27 transgenic rats is partly dependent on activation of the sympathetic nervous system, but the role of ganglionic transmission is unknown. We assessed indices of synaptic plasticity (post-tetanic short-term potentiation [PTP] and long-term potentiation [LTP]) and sympathetic ganglionic transmission without tetany in superior cervical ganglia (SCG) of Hannover Sprague-Dawley rats (HnSD) versus (mRen2)27 rats. There were no differences in decay time constants [PTP=9 minutes; LTP=120 to 150 minutes in both (mRen2)27 and HnSD]. However, angiotensin (Ang) II increased PTP and LTP in SCG isolated from (mRen2)27 rats to a greater extent than HnSD. Candesartan (an AT
1
antagonist) blocked the potentiation in both groups. Without a preceding tetanic pulse, 16-nM Ang II induced similar significant increases in ganglionic transmission of ≈14% in both strains. Assessment of Ang II receptors by
125
I-[Sar
1
Thr
8
]-Ang II binding showed that the AT
1
-receptor subtype predominates in the ganglia. The density of receptors in the SCG was comparable in (mRen2)27 and HnSD rats, whether measured in tissue from ganglia removed and frozen versus ganglia used in the transmission testing, suggesting that upregulation of receptors in vitro after removal of SCG did not occur. The divergence of effects of Ang II on LTP and PTP [greater in (mRen2)27 than HnSD] and nontetany ganglionic transmission (similar in both strains) may reflect different locations of receptors (pre- versus postsynaptic) or different signaling mechanisms involved in the two responses. We suggest that functional Ang II receptors in SCG mediate physiological actions of Ang II on ganglionic transmission and may play a pivotal role in hypertension.
Decrease in Hypothalamic Gamma Adducin in Rat Models of Hypertension
Authors: Yang Hong , Reaves Phyllis Y. , Katovich Michael J. , Raizada Mohan K.
Published: January 2004

We have previously shown that a decrease in hypothalamic gamma adducin (γ-adducin) is associated with hypertension in the spontaneously hypertensive rat (SHR). In view of many inherent issues with SHR, our objective in the present study was to provide proof of this concept with the use of 2 nongenetic rat models of hypertension. Subcutaneous angiotensin II (Ang II) infusion for 2 weeks (55 ng/kg per day) resulted in an increase in blood pressure (BP) of 18 mm Hg. This was associated with a 70% decrease in hypothalamic γ-adducin. Concomitant administration of losartan attenuated the development of hypertension and a decrease in γ-adducin. Deoxycorticosterone acetate salt-induced hypertension also caused a 70% decrease in hypothalamic γ-adducin. Finally, neuronal cultures from neonatal rat brains were incubated with 100 nmol/L Ang II for 4 hours to mimic the in vivo Ang II infusion rat model. This chronic incubation with Ang II resulted in a 60% decrease in the neuronal γ-adducin. Taken together, these observations strengthen our hypothesis that a decrease in hypothalamic γ-adducin is linked to hypertension.