bluuebunny/crossref_metadata_2025 huggingface dataset:
Norovirus Proteinase-Polymerase and Polymerase Are Both Active Forms of RNA-Dependent RNA Polymerase
Authors: Belliot Gaël , Sosnovtsev Stanislav V. , Chang Kyeong-Ok , Babu Vijay , Uche Uzo , Arnold Jamie J. , Cameron Craig E. , Green Kim Y.
Published: January 2005

In vitro mapping studies of the MD145 norovirus (
Caliciviridae
) ORF1 polyprotein identified two stable cleavage products containing the viral RNA-dependent RNA polymerase (RdRp) domains: ProPol (a precursor comprised of both the proteinase and polymerase) and Pol (the mature polymerase). The goal of this study was to identify the active form (or forms) of the norovirus polymerase. The recombinant ProPol (expressed as Pro
−
Pol with an inactivated proteinase domain to prevent autocleavage) and recombinant Pol were purified after synthesis in bacteria and shown to be active RdRp enzymes. In addition, the mutant His-E1189A-ProPol protein (with active proteinase but with the natural ProPol cleavage site blocked) was active as an RdRp, confirming that the norovirus ProPol precursor could possess two enzymatic activities simultaneously. The effects of several UTP analogs on the RdRp activity of the norovirus and feline calicivirus Pro
−
Pol enzymes were compared and found to be similar. Our data suggest that the norovirus ProPol is a bifunctional enzyme during virus replication. The availability of this recombinant ProPol enzyme might prove useful in the development of antiviral drugs for control of the noroviruses associated with acute gastroenteritis.
Amyloid in the cardiovascular system: a review
Authors: Kholová I , Niessen H W M
Published: January 2005

The cardiovascular system is a common target of amyloidosis. This review presents the current clinical and diagnostic approach to amyloidosis, with the emphasis on cardiovascular involvement. It summarises recent nomenclature, classification, and pathogenesis of amyloidosis. In addition, non-invasive possibilities are discussed, together with endomyocardial biopsies in the diagnosis of cardiac amyloidosis. Finally, recent advances in treatment and prognostic implications are presented.
Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma
Authors: Santini D , Tonini G , Vecchio F M , Borzomati D , Vincenzi B , Valeri S , Antinori A , Castri F , Coppola R , Magistrelli P , Nuzzo G , Picciocchi A
Published: January 2005

Background:There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma.

Aims:To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer.

Methods:All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL).

Results:Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p  =  0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p  =  0.001, p  =  0.01, and p  =  0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p  =  0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p  =  0.020).

Conclusions:These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.
Eruptive tufted angiomas in a patient with Crohn’s disease
Authors: Al-Za’abi A M , Ghazarian D , Greenberg G R , Shaw J C
Published: January 2005

Angioblastoma is a rare, benign vascular tumour composed of undifferentiated mesenchymal cells with a tendency to form lumina. This entity was first described by Nakagawa in 1949 as angioblastoma, and Wilson Jones was the first to use the term “tufted angioma” in 1976. Tufted angiomas usually occur in infancy and spread slowly. This report describes lesions from the right side of the forehead, forearms, and thighs of a 24 year old man with a four year history of Crohn’s disease, who was receiving infliximab in addition to long standing azathioprine and ciprofloxacillin. He developed numerous small itchy erythematous vascular appearing papules, which on histological examination resembled tufted angiomas, showing the classic “cannon ball” appearance. The lesions regressed within three months. This case may represent an eruptive acquired tufted angioma in which immunosuppression or drug induced modification of angiogenesis played a role in its development and regression. One previous case of eruptive tufted angioma has been reported in an immunosuppressed patient.
Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion
Authors: Suzuki T , Izumoto S , Fujimoto Y , Maruno M , Ito Y , Yoshimine T
Published: January 2005

Background/Aims:In patients with gliomatosis cerebri (GC), glial fibrillary acidic protein (GFAP) positive cells invade the entire brain, particularly the white matter. Because the nosological definition and histogenesis of GC remain controversial, the morphology and immunohistochemical staining patterns of neoplastic GC cells were compared with those of other gliomas.

Methods:An immunohistochemical analysis of neoplastic cells from four patients with GC and 20 with astrocytic tumours using antibodies against Ki-67, GFAP, and L1, the last of which is a neural cell adhesion molecule putatively related to glioma invasion.

Results:GC tumour cells can be divided into two types, those mainly composed of strongly GFAP and L1 positive gemistocytic cells, the other composed of small, GFAP and L1 negative spindle shaped cells. The two types did not differ with respect to Ki-67 positivity. Cells from patients with other gliomas were positive for GFAP but concurrent L1 expression was negative or weakly positive.

Conclusion:The strong expression of L1 in patients with GC and its poor expression in the 20 patients with other types of glioma, including those with GFAP positive gemistocytic astrocytomas, suggest that L1 expression may play a role in the histogenesis of GC.
Nestin as a diagnostic and prognostic marker: immunohistochemical analysis of its expression in different tumours
Authors: Ehrmann J , Kolář Z , Mokrý J
Published: January 2005

The designation NESTIN refers to a member of the family of intermediate filaments and comes from the fact that this protein is expressed mainly in neuroepithelial stem cells. However, nestin is not expressed in mature elements and terminal cell differentiation is associated with loss of immunoreactivity to this protein. Therefore, immunohistochemical assessment of nestin expression might be useful to differentiate between mature and immature elements. The aim of this study was to analyse nestin expression in various tumours of neuroectodermal and vascular origin and to determine whether its detection has practical relevance. The results indicate that the immunohistochemical detection of nestin expression could be useful in astrocytomas and malignant melanomas, where it could be used as an auxiliary indicator of dedifferentiation and progression. Because of the weak and heterogeneous expression of nestin in neurinomas, phaeochromocytomas, and carcinoids, nestin detection in these lesions is of little practical use.
Perianal apocrine adenocarcinoma arising in a benign apocrine adenoma; first case report and review of the literature
Authors: MacNeill K N , Riddell R H , Ghazarian D
Published: January 2005

Benign apocrine lesions have been described in the anogenital region, although according to the World Health Organisation convincing examples of anal apocrine adenocarcinomas have not been published. This report describes the case of an invasive apocrine adenocarcinoma arising in a benign adenoma in the perianal region of a 45 year old woman. The origin and invasiveness are supported by histological and immunohistochemical studies.
Imprinting, expression, and localisation of DLK1 in Wilms tumours
Authors: Fukuzawa R , Heathcott R W , Morison I M , Reeve A E
Published: January 2005

Background:Loss of imprinting (LOI) of the H19/IGF2 domain is a common feature of Wilms tumour. The GTL2/DLK1 domain is also imprinted and is structurally similar to H19/IGF2. The question arises as to whether DLK1 also undergoes LOI in Wilms tumour, or whether the LOI mechanism is restricted to the H19/IGF2 domain.

Aim:To investigate the imprinting status of DLK1 in Wilms tumours with IGF2 LOI. The cellular localisation of DLK1 in the tumours was also examined.

Methods:DLK1 expression was measured by quantitative real time polymerase chain reaction (Q-PCR) in 30 Wilms tumours that had previously been classified according to whether they had IGF2 LOI, WT1 mutations, or 11p15.5 loss of heterozygosity. Allele specific expression of DLK1 was examined by direct sequencing using a DLK1 exon 5 polymorphism (rs1802710). Immunohistochemical analysis of DLK1 was performed on 13 tumours and two intralobar nephrogenic rests, in addition to two fetal kidneys and one fetal skeletal muscle sample.

Results:Ten of 30 tumours were heterozygous for rs1802710 and all tumours showed retention of imprinting of DLK1. Moderate to high expression of DLK1 was detected by Q-PCR in nine of 13 tumours with myogenic differentiation. Immunohistochemical expression of DLK1 was detected in the myogenic elements.

Conclusion:LOI does not occur at the GTL2/DLK1 domain in Wilms tumour. This finding suggests that LOI at 11p15.5 does not reflect non-specific disruption of a shared imprinting mechanism. DLK1 expression in Wilms tumour might reflect the presence of myogenic differentiation, rather than an alteration of its imprinting status.
REDOX REGULATION: A Broadening Horizon
Authors: Buchanan Bob B. , Balmer Yves
Published: January 2005

Initially discovered in the context of photosynthesis, regulation by change in the redox state of thiol groups (S−S ↔ 2SH) is now known to occur throughout biology. Several systems, each linking a hydrogen donor to an intermediary disulfide protein, act to effect changes that alter the activity of target proteins: the ferredoxin/ thioredoxin a small protein, reduced enzymatically by NADPH or ferredoxin, that is active in thiol/disulfide exchange and results in regulation or substrate conversion system, comprised of reduced ferredoxin, a thioredoxin, and the enzyme, ferredoxin-thioredoxin reductase; the NADP/thioredoxin system, including NADPH, a thioredoxin, and NADP-thioredoxin reductase; and the glutathione/ glutaredoxin a small protein, reduced by glutathione, that is active in thiol/disulfide exchange and results in regulation or substrate conversion system, composed of reduced glutathione and a glutaredoxin. A related disulfide protein, protein disulfide isomerase (PDI) acts in protein assembly. Regulation linked to plastoquinone and signaling induced by reactive oxygen species ( ROS reactive oxygen species ) and other agents are also being actively investigated. Progress made on these systems has linked redox to the regulation of an increasing number of processes not only in plants, but in other types of organisms as well. Research in areas currently under exploration promises to provide a fuller understanding of the role redox plays in cellular processes, and to further the application of this knowledge to technology and medicine.
Modeling Water, the Hydrophobic Effect, and Ion Solvation
Authors: Dill Ken A. , Truskett Thomas M. , Vlachy Vojko , Hribar-Lee Barbara
Published: January 2005

▪ Abstract  Water plays a central role in the structures and properties of biomolecules—proteins, nucleic acids, and membranes—and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global properties—water's thermodynamics, phase diagram, and solvation properties, for example—and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of water—as a pure liquid and as a solvent—derive from the geometric and hydrogen bonding properties of water.
Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart
Authors: Patrick Casey B. , McHowat Jane , Rosenberger Thad A. , Rapoport Stanley I. , Murphy Eric J.
Published: January 2005

Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 μCi/kg of either [1-14C]palmitic acid ([1-14C]16:0) or [1-14C]arachidonic acid ([1-14C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient λ was increased in [1-14C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-14C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of β-oxidation. In [1-14C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60–84%) and turnover value (56–85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A2activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A2activity.
Role of adenosine A1 and A3 receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury
Authors: Shneyvays Vladimir , Leshem Dorit , Zinman Tova , Mamedova Liaman K. , Jacobson Kenneth A. , Shainberg Asher
Published: January 2005

Activation of either the A1 or the A3 adenosine receptor (A1R or A3R, respectively) elicits delayed cardioprotection against infarction, ischemia, and hypoxia. Mitochondrial contribution to the progression of cardiomyocyte injury is well known; however, the protective effects of adenosine receptor activation in cardiac cells with a respiratory chain deficiency are poorly elucidated. The aim of our study was to further define the role of A1R and A3R activation on functional tolerance after inhibition of the terminal link of the mitochondrial respiratory chain with sodium azide, in a state of normoxia or hypoxia, compared with the effects of the mitochondrial ATP-sensitive K+ channel opener diazoxide. Treatment with 10 mM sodium azide for 2 h in normoxia caused a considerable decrease in the total ATP level; however, activation of adenosine receptors significantly attenuated this decrease. Diazoxide (100 μM) was less effective in protection. During treatment of cultured cardiomyocytes with hypoxia in the presence of 1 mM sodium azide, the A1R agonist 2-chloro- N6-cyclopentyladenosine was ineffective, whereas the A3R agonist 2-chloro- N6-iodobenzyl-5′- N-methylcarboxamidoadenosine (Cl-IB-MECA) attenuated the decrease in ATP level and prevented cell injury. Cl-IB-MECA delayed the dissipation in the mitochondrial membrane potential during hypoxia in cells impaired in the mitochondrial respiratory chain. In cells with elevated intracellular Ca2+ concentration after hypoxia and treatment with NaN3 or after application of high doses of NaN3, Cl-IB-MECA immediately decreased the elevated intracellular Ca2+ concentration toward the diastolic control level. The A1R agonist was ineffective. This may be especially important for the development of effective pharmacological agents, because mitochondrial dysfunction is a leading factor in the pathophysiological cascade of heart disease.
Nonlinear interactions in renal blood flow regulation
Authors: Marsh Donald J. , Sosnovtseva Olga V. , Chon Ki H. , Holstein-Rathlou Niels-Henrik
Published: January 2005

We have developed a model of tubuloglomerular feedback (TGF) and the myogenic mechanism in afferent arterioles to understand how the two mechanisms are coupled. This paper presents the model. The tubular model predicts pressure, flow, and NaCl concentration as functions of time and tubular length in a compliant tubule that reabsorbs NaCl and water; boundary conditions are glomerular filtration rate (GFR), a nonlinear outflow resistance, and initial NaCl concentration. The glomerular model calculates GFR from a change in protein concentration using estimates of capillary hydrostatic pressure, tubular hydrostatic pressure, and plasma flow rate. The arteriolar model predicts fraction of open K channels, intracellular Ca concentration (Cai), potential difference, rate of actin–myosin cross bridge formation, force of contraction, and length of elastic elements, and was solved for two arteriolar segments, identical except for the strength of TGF input, with a third, fixed resistance segment representing prearteriolar vessels. The two arteriolar segments are electrically coupled. The arteriolar, glomerular, and tubular models are linked; TGF modulates arteriolar circumference, which determines vascular resistance and glomerular capillary pressure. The model couples TGF input to voltage-gated Ca channels. It predicts autoregulation of GFR and renal blood flow, matches experimental measures of tubular pressure and macula densa NaCl concentration, and predicts TGF-induced oscillations and a faster smaller vasomotor oscillation. There are nonlinear interactions between TGF and the myogenic mechanism, which include the modulation of the frequency and amplitude of the myogenic oscillation by TGF. The prediction of modulation is confirmed in a companion study ( 28 ).
Effects of menstrual cycle and physical training on heat loss responses during dynamic exercise at moderate intensity in a temperate environment
Authors: Kuwahara Tomoko , Inoue Yoshimitsu , Abe Miyako , Sato Yuki , Kondo Narihiko
Published: January 2005

We evaluated the effects of the menstrual cycle and physical training on heat loss (sweating and cutaneous vasodilation) responses during moderate exercise in a temperate environment. Ten untrained (group U) and seven endurance-trained (group T) women (maximal O2 uptake of 36.7 ± 1.1 vs. 49.4 ± 1.7 ml·kg−1·min−1, respectively; P < 0.05) performed a cycling exercise at 50% maximal O2 uptake for 30 min during both the midfollicular and midluteal menstrual phase in a temperate environment (ambient temperature of 25°C, relative humidity of 45%). In group U, plasma levels of estrone, estradiol, and progesterone at rest and esophageal temperature (Tes) during exercise were significantly higher during the midluteal than during the midfollicular phase ( P < 0.05). Sweating rate and cutaneous blood flow (measured via laser-Doppler flowmetry) on the chest, back, forearm, and thigh were lower during the midluteal than during the midfollicular phase during exercise. Tes threshold for heat loss responses was significantly higher and sensitivity of the heat loss responses was significantly lower in the midluteal than in the midfollicular phase, regardless of body site. These effects of the menstrual cycle in group U were not observed in group T. The sweating rate and cutaneous blood flow were significantly higher in group T than in group U, regardless of menstrual phase or body site. Tes threshold for heat loss responses was significantly lower and sensitivity of heat loss responses was significantly greater in group T than in group U in the midluteal phase; however, sensitivity of the sweating response was significantly greater in the midfollicular phase. These results suggest that heat loss responses in group U were inhibited in the midluteal phase compared with in the midfollicular phase. Menstrual cycle had no remarkable effects in group T. Physical training improved heat loss responses, which was more marked in the midluteal than in the midfollicular phase.
Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide
Authors: Jensen Dennis , Wolfe Larry A. , Slatkovska Lubomira , Webb Katherine A. , Davies Gregory A. L. , O'Donnell Denis E.
Published: January 2005

This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups ( n = 11) of pregnant subjects (PG, gestational age, 36.5 ± 0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic CO2 rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal Pco2 increased, whereas end-tidal Po2 was maintained at a constant hyperoxic level. The point at which ventilation (V̇e) began to rise as end-tidal Pco2 increased was identified as the central chemoreflex ventilatory recruitment threshold for CO2 (VRTco2). V̇e levels below (basal V̇e) and above (central chemoreflex sensitivity) the VRTco2 were determined. The VRTco2 was significantly lower in the PG vs. CG (40.5 ± 0.8 vs. 45.8 ± 1.6 Torr), and both basal V̇e (14.8 ± 1.1 vs. 9.3 ± 1.6 l/min) and central chemoreflex sensitivity (5.07 ± 0.74 vs. 3.16 ± 0.29 l·min−1·Torr−1) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial Pco2 with basal V̇e, central chemoreflex sensitivity, and the VRTco2. The VRTco2 was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to CO2. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe.
Global stability of delayed Hopfield neural networks underdynamical thresholds
Authors: Zhang Fei-Yu , Li Wan-Tong
Published: January 2005

We study dynamical behavior of a class of cellular neural networks
system with distributed delays under dynamical thresholds. By using topological degree theory and Lyapunov functions, some new criteria ensuring the existence, uniqueness, global asymptotic stability, and global exponential stability of equilibrium point are derived. In particular, our criteria generalize and improve some known results in the literature.
Heterogeneous traders, price‐volume signals, and complex asset price dynamics
Authors: Westerhoff Frank H.
Published: January 2005

We seek to develop a novel asset pricing model with heterogeneous traders. Fundamental traders expect that asset prices converge towards their
intrinsic values, whereas chart traders rely on both price and volume signals to determine their orders. To be precise, the larger the trading volume, the more they believe in the persistence of the current price trend. Simulations of our nonlinear deterministic
model reveal that interactions between fundamentalists and chartists may cause intricate endogenous price fluctuations. Contrary to the intuition, we find that chart trading may increase market stability.
Approximation of solutions to retarded differential equations with applications to population dynamics
Authors: Bahuguna D. , Muslim M.
Published: January 2005

We consider a retarded differential equation with applications to population dynamics. We establish the convergence of a finite‐dimensional approximations of a unique solution, the existence and uniqueness of which are also proved in the process.
Double‐barriers‐reflected BSDEs with jumps and viscosity solutions of parabolic integrodifferential PDEs
Authors: Harraj N. , Ouknine Y. , Turpin I.
Published: January 2005

We give a probabilistic interpretation of the viscosity solutions of parabolic integrodifferential partial equations with two obstacles via the solutions of forward‐backward stochastic differential equations with jumps.
Approximate controllability of delayed semilinear control systems
Authors: Wang Lianwen
Published: January 2005

We deal with the approximate controllability of control systems governed by delayed semilinear differential equations . Various sufficient conditions for approximate controllability have been obtained; these results usually require some complicated and limited assumptions. Results in this paper provide sufficient conditions for the approximate controllability of a class of delayed semilinear control systems under natural assumptions.
On the coefficients of variation of uptime and downtime inmanufacturing equipment
Authors: Li Jingshan , Meerkov Semyon M.
Published: January 2005

It was reported in the literature that the coefficients of variation of uptime and downtime of manufacturing equipment are often less than 1. This technical paper is intended to provide an analytical explanation of this phenomenon. Specifically, it shows that the distributions of uptime and downtime have the coefficients of variation less than 1 if the breakdown and repair rates are increasing functions of time.
On pole‐placement controllers for linear time‐delay systems withcommensurate point delays
Authors: de la Sen M.
Published: January 2005

We investigate the exact and approximate spectrum assignment
properties associated with realizable output‐feedback pole‐placement‐type
controllers for single‐input single‐output linear time‐invariant time‐delay systems with commensurate point delays. The controller synthesis problem is discussed through the solvability of a set of coupled Diophantine equations of polynomials. An extra complexity is
incorporated in the above design to cancel extra unsuitable dynamics being generated when solving the above Diophantine equations. Thus, the complete controller tracks any arbitrary prefixed (either finite or delay‐dependent) closed‐loop spectrum. However, if the controller is simplified by deleting the above‐mentioned extra complexity, then robust stability and approximated spectrum assignment are still achievable for a certain sufficiently small amount of delayed dynamics. Finally, the approximate spectrum assignment and robust stability problems are revisited under plant disturbances if the
nominal controller is maintained. In the current approach, the finite spectrum assignment is only considered as a particular case of the designer′s choice of a (delay‐dependent) arbitrary spectrum assignment objective.
Conservation laws for equations related to soil water equations
Authors: Khalique C. M. , Mahomed F. M.
Published: January 2005

We obtain all nontrivial conservation laws for a class of (2+1) nonlinear evolution partial differential equations which are related to the soil water equations. It is also pointed out that nontrivial conservation laws exist for certain classes of
equations which admit point symmetries. Moreover, we associate symmetries with conservation laws for special classes of these equations.
A filtered renewal process as a model for a river flow
Authors: Lefebvre Mario
Published: January 2005

Various models, based on a filtered Poisson process, are used for
the flow of a river. The aim is to forecast the next peak value of the flow, given that another peak was observed not too long ago. The most realistic model is the one when the time between the successive peaks does not have an exponential
distribution, as is often assumed. An application to the Delaware River, in the USA, is presented.
Real‐time feedback control of computer networks based on predicted state estimation
Authors: Ahmed N. U. , Song Hui
Published: January 2005

We present a real‐time feedback control strategy to optimize the
dynamic performance of a computer communication network. In previous studies closely related to this topic, feedback delay, arising from communication delay, was shown to degrade system performance. Considering this negative impact of delay, we propose
a new control law which predicts the traffic in advance and exercises control based on the predicted traffic. We demonstrate through simulation experiments that the predictive feedback control law substantially improves the system performance.
Differential Effect of Experimental Hypertension and Hypercholesterolemia on Adventitial Remodeling
Authors: Herrmann Joerg , Samee Saquib , Chade Alejandro , Porcel Martin Rodriguez , Lerman Lilach O. , Lerman Amir
Published: January 2005

Objective—

Intima-media remodeling, as frequently assessed by changes in the external elastic lamina-to-lumen area (EELLA), is well-described in coronary artery disease in contrast to adventitial remodeling, especially in the early disease stage.

Method and Results—

Female domestic pigs were randomized to one of the following 12-week treatment groups: normal diet (N; n=6), high-cholesterol diet (HC; n=6), or renovascular hypertension (HT; n=4). Low-density lipoprotein (LDL) cholesterol serum concentration was higher in HC than in N and HT (395.5±106 versus 38.6±14 and 37.2±6.8 mg/dL;
P
<0.05 for both). Mean arterial pressure was higher in HT than in N and HC (141.3±21 versus 107.4±8.9 and 109.4±7.8 mm Hg;
P
<0.05 for both). EELLA ratio, as assessed by morphometry, was similar in N, HC, and HTN (1.03±0.32 versus 0.95±0.29 and 1.01±0.09;
P
<0.05 for both). Coronary vasa vasorum density, as assessed by 3-dimensional micro-computed tomography, was higher in HC than in N and HT (3.4±1.0 versus 1.9±0.3 and 2.0±1.2;
P
<0.05 for both). In contrast, immunostaining showed a higher collagen III content and the presence of adventitial myofibroblasts in HT compared with N and HC.

Conclusions—

The current study suggests that adventitial remodeling precedes intima and media remodeling of coronary arteries early after exposure to hypercholesterolemia and hypertension, with distinct qualitative differences between them.
Modulation of Clusterin Isoforms Is Associated With All-
Trans
Retinoic Acid–Induced Proliferative Arrest and Apoptosis of Intimal Smooth Muscle Cells
Authors: Orlandi Augusto , Pucci Sabina , Ciucci Alessandro , Pichiorri Flavia , Ferlosio Amedeo , Spagnoli Luigi Giusto
Published: January 2005

Objectives—

Clusterin is a heterodimeric glycoprotein which is implicated in several biological processes. The nuclear (n-CLU) and cytoplasmic secreted (s-CLU) isoforms have recently been described, but their role is still unclear. The aim of this study is to investigate the expression of clusterin and its isoforms during proliferative arrest and apoptosis of vascular smooth muscle cells (SMCs).

Methods and Results—

Clusterin expression was evaluated by immunohistochemistry and Western blotting in human arteries and rat aortas. In human diffuse myointimal thickening, clusterin was detected in cell cytoplasm and extracellular space, whereas it was practically absent in the media. In rat aortas 15 days after ballooning, intimal cells (IT cells) overexpressed s-CLU and n-CLU, the latter mainly in the inner neointima; clusterin expression decreased at 60 days. In vitro, IT cells maintained high clusterin expression and its antisense markedly reduced proliferation and increased apoptosis. Western blotting showed that all-
trans
retinoic acid-induced proliferative arrest and increased α-smooth muscle actin expression did associate to s-CLU and B-myb reduction, whereas bax-related apoptosis was associated to a shift from the s-CLU to n-CLU isoform.

Conclusions—

Clusterin overexpression characterized neointimal SMCs; s-CLU expression decreased in IT cells during all-
trans
retinoic acid-induced proliferative arrest and redifferentiation, whereas n-CLU overexpression was characteristic of apoptosis.
Block of Inward Rectifying K
+
Channels (K
IR
) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature
Authors: Dwivedi R. , Saha S. , Chowienczyk P.J. , Ritter J.M.
Published: January 2005

Objective—

To investigate the possible involvement of inward rectifying K
+
channels (K
IR
) in the response of human resistance vessels to bradykinin in vivo.

Methods and Results—

Drugs were administered via the brachial artery in healthy male volunteers and forearm blood flow was measured by venous occlusion plethysmography. Inhibition of K
IR
by barium chloride (4 μmol min
−1
) alone or with additional inhibition of Na
+
/K
+
ATPase (ouabain 2.7 μmol min
−1
) reduced responses to bradykinin (30 pmol min
−1
), by 26±8.3% and 36±7.2%, respectively (each
P
<0 0.05). Barium with ouabain plus inhibitors of prostaglandin (PG) and nitric oxide synthesis inhibited but did not abolish responses to bradykinin (51±2.8% inhibition;
P
<0.01); norepinephrine (240 pmol min
−1
) caused similar reduction of baseline blood flow, as did this combination of inhibitors, but did not significantly inhibit the response to bradykinin. Barium plus ouabain did not significantly reduce responses to acetylcholine or albuterol.

Conclusion—

A component of the vasodilator response to bradykinin in human forearm vasculature is mediated by K
IR
.
Fluvastatin Prevents Vascular Hyperplasia by Inhibiting Phenotype Modulation and Proliferation Through Extracellular Signal-Regulated Kinase 1 and 2 and p38 Mitogen-Activated Protein Kinase Inactivation in Organ-Cultured Artery
Authors: Sakamoto Kenichi , Murata Takahisa , Chuma Hiroko , Hori Masatoshi , Ozaki Hiroshi
Published: January 2005

Objective—

We examined the inhibitory mechanisms of fluvastatin on FBS-induced vascular hypertrophy assessed by organ-cultured rat tail artery.

Methods and Results—

After 5 days of culture with 10% FBS, hyperplastic morphological changes in the media layer were induced. Treatment with 1 μmol/L fluvastatin significantly inhibited these changes. In the FBS-cultured arteries, the protein expression ratio of α-actin/β-actin was significantly decreased, indicating the change to synthetic phenotype. Fluvastatin restored the decreased expression ratio, and the addition of mevalonate (100 μmol/L) suppressed this recovery. In accordance with the synthetic morphological changes, the absolute force of contractions induced by stimuli was decreased. Fluvastatin treatment also restored the decreased contractility, and the addition of mevalonate suppressed this recovery. In the arteries cultured with FBS, extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation were significantly increased. Fluvastatin inhibited these phosphorylations, and mevalonate prevented the action of fluvastatin.

Conclusion—

These results suggest that fluvastatin inhibits vascular smooth muscle phenotype modulation to synthetic phenotype and proliferation by inhibiting the local metabolic pathway of cholesterol in smooth muscle cells, which inhibits hyperplastic changes in the vascular wall. The antihyperplastic actions by statins may be induced by inhibiting the ERK1/2 and p38MAPK activities, possibly through inhibition of prenylated Ras.
Apolipoprotein E Promotes the Regression of Atherosclerosis Independently of Lowering Plasma Cholesterol Levels
Authors: Raffai Robert L. , Loeb Samuel M. , Weisgraber Karl H.
Published: January 2005

Objective—The mechanisms by which apolipoprotein E (apoE) can promote the regression of atherosclerosis are not well understood. This study examined whether apoE can promote atherosclerosis regression independently of lowering plasma cholesterol levels.

Methods and Results—We studied hypomorphic apoE mice (Apoeh/h), which express an apoE4-like form of mouse apoE at ≈2% to 5% of normal levels in plasma and are normolipidemic. After 18 weeks of diet-induced hypercholesterolemia, which resulted in advanced aortic atherosclerotic lesions composed of a lipid-rich layer of foam cells covering a fibrotic core, 2 groups of mice were fed a chow diet for 16 weeks. One group continued to express low levels of apoE; the other was induced to express physiological levels of plasma apoE by Cre-mediated recombination of the hypomorphicApoeallele. In both groups, plasma cholesterol levels fell rapidly to similar levels, and histological analysis at 16 weeks revealed elimination of the foam-cell layer. However, physiological levels of plasma apoE also enhanced the removal of neutral lipids from the fibrotic cores.

Conclusion—These findings demonstrate for the first time that apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels.
Pitavastatin Inhibits Remnant Lipoprotein-Induced Macrophage Foam Cell Formation Through ApoB48 Receptor–Dependent Mechanism
Authors: Kawakami Akio , Tani Mariko , Chiba Tsuyoshi , Yui Katsumasa , Shinozaki Shohei , Nakajima Katsuyuki , Tanaka Akira , Shimokado Kentaro , Yoshida Masayuki
Published: January 2005

Objective—

Atherogenic remnant lipoproteins (RLPs) are known to induce foam cell formation in macrophages in vitro and in vivo. We examined the involvement of apoB48 receptor (apoB48R), a novel receptor for RLPs, in that process in vitro and its potential regulation by pitavastatin.

Methods and Results—

THP-1 macrophages were incubated in the presence of RLPs (20 mg cholesterol/dL, 24 hours) isolated from hypertriglyceridemic subjects. RLPs significantly increased intracellular cholesterol ester (CE) and triglyceride (TG) contents (4.8-fold and 5.8-fold, respectively) in the macrophages. Transfection of THP-1 macrophages with short interfering RNA (siRNA) against apoB48R significantly inhibited RLP-induced TG accumulation by 44%. When THP-1 macrophages were pretreated with pitavastatin (5 μmol/L, 24 hours), the expression of apoB48R was significantly decreased and RLP-induced TG accumulation was reduced by 56%. ApoB48R siRNA also inhibited TG accumulation in THP-1 macrophage induced by β–very-low-density lipoprotein derived from apoE−/− mice by 58%, supporting the notion that apoB48R recognizes and takes-up RLPs in an apoE-independent manner.

Conclusions—

RLPs induce macrophage foam cell formation via apoB48R. Pitavastatin inhibits RLP-induced macrophage foam cell formation. The underlying mechanism involves, at least in part, inhibition of apoB48R-dependent mechanism. Our findings indicate a potential role of apoB48R in atherosclerosis.
GATA-6 Regulates Genes Promoting Synthetic Functions in Vascular Smooth Muscle Cells
Authors: Lepore John J. , Cappola Thomas P. , Mericko Patricia A. , Morrisey Edward E. , Parmacek Michael S.
Published: January 2005

Objective—

Previous studies suggested the zinc-finger transcription factor GATA-6 inhibits vascular smooth muscle cell (VSMC) proliferation and promotes the contractile VSMC phenotype. The objective of this study was to identify bona fide target genes regulated by GATA-6 in VSMCs.

Methods and Results—

Microarray analyses were performed comparing mRNA from rat aortic smooth muscle cells (SMCs) infected with either adenovirus encoding a dominant-negative GATA-6/engrailed fusion protein or with control adenovirus. These studies identified 122 genes differentially expressed by at least 2-fold, including multiple genes involved in cell–cell signaling and cell–matrix interactions. Among these, endothelin-1 and the angiotensin type
1a
(AT
1a
) receptor are known to be induced in VSMCs in response to inflammatory stimuli and to be expressed in a GATA-dependent manner in cardiac myocytes in response to hemodynamic stress. Consistent with these findings, the endothelin-1 and AT
1a
receptor promoters were activated by forced expression of GATA-6 and repressed by forced expression of GATA-6/engrailed. Surprisingly, genes encoding SMC contractile proteins were not altered, and myocardin-induced SMC differentiation was not impaired in GATA-6
−/−
embryonic stem cells.

Conclusions—

These data demonstrate that in VSMCs, GATA-6 regulates a set of genes associated with synthetic SMC functions and suggest that this transcriptional pathway may be independent from myocardin-induced SMC differentiation.
Role of Mitochondrial Permeability Transition Pore in Coated-Platelet Formation
Authors: Remenyi Gyula , Szasz Robert , Friese Paul , Dale George L.
Published: January 2005

Objective—

Coated-platelets are a subset of cells observed during costimulation of platelets with collagen and thrombin. Important characteristics of coated-platelets include retention of multiple α-granule proteins and expression of phosphatidylserine on the cell surface. The mitochondrial permeability transition pore (MPTP) is a key step in apoptosis and is suggested to be involved in some forms of platelet activation. The objective of this study was to examine the role of MPTP in the synthesis of coated-platelets.

Methods and Results—

Flow cytometric analysis of coated-platelet production was used to examine the impact of pharmacological effectors of MPTP formation. Cyclosporin A, coenzyme Q, and bongkrekic acid all inhibit MPTP formation as well as production of coated-platelets. Phenylarsine oxide and diamide, both potentiators of MPTP formation, stimulate coated-platelet synthesis. Atractyloside, another inducer of MPTP formation, does not affect the percentage of coated-platelets synthesized; however, it does increase the level of phosphatidylserine exposed on the surface of coated-platelets.

Conclusions—

These findings indicate that MPTP formation is an integral event in the synthesis of coated-platelets. Although the exact function of the MPTP remains to be determined, these data support a growing body of evidence that apoptosis-associated events are vital components of the platelet activation process.
Renal Angiotensin II Type-2 Receptors Are Upregulated and Mediate the Candesartan-Induced Natriuresis/Diuresis in Obese Zucker Rats
Authors: Hakam Amer C. , Hussain Tahir
Published: January 2005

Recently, there has been a growing interest in studying the role of angiotensin II type-2 (AT
2
) receptor in renal/cardiovascular function in pathological conditions. The present study was designed to determine the functional role of the AT
2
receptors on natriuresis/diuresis and compare the level of the tubular AT
2
receptor expression in obese and lean Zucker rats (12 weeks old). Under anesthesia, candesartan (angiotensin II type 1 [AT
1
]–specific antagonist; 100 μg/kg bolus) produced natriuresis/diuresis to a greater degree in obese than in lean rats. The specific AT
2
antagonist PD123319 (50 μg/kg per minute) after candesartan administration abolished the natriuretic/diuretic effects of candesartan in obese rats but not in lean rats. Infusion of AT
2
receptor agonist, CGP-42112A (1 μg/kg per minute), produced greater increase in sodium and urine excretion over basal in obese than in lean rats. The presence of the AT
2
receptor expression in the brush-border and basolateral membranes was confirmed by Western blotting using specific antibody and antigen-blocking peptide. Densitometric analysis of the bands revealed ≈1.5- to 2.0-fold increase in the AT
2
receptor proteins in both membranes of obese compared with lean rats. Our results suggest upregulation of the AT
2
receptors, which play a role in mediating the natriuretic/diuretic effects of AT
1
receptor blockers in obese Zucker rats. We speculate that AT
2
receptors, by promoting sodium excretion, may protect obese Zucker rats against blood pressure increase associated with sodium and water retention.
Short- and Long-Term Incidence of Stroke in White-Coat Hypertension
Authors: Verdecchia Paolo , Reboldi Gian Paolo , Angeli Fabio , Schillaci Giuseppe , Schwartz Joseph E. , Pickering Thomas G. , Imai Yutaka , Ohkubo Takayoshi , Kario Kazuomi
Published: January 2005

White-coat hypertension (WCH) has been associated with a low risk for stroke, but long-term data are scanty. We analyzed individual data from 4 prospective cohort studies from the United States, Italy, and Japan that used comparable methodology for 24-hour noninvasive ambulatory blood pressure monitoring (ABPM). Overall, 4406 subjects with essential hypertension and 1549 healthy normotensive controls who were untreated at the time of initial ABPM were followed for a median of 5.4 years up to censoring or occurrence of a first stroke. At entry, mean age of subjects was 56 years (range 18 to 97). Prevalence of WCH was 9%. During follow-up, there were 213 new cases of stroke. Stroke rate (×100 person years) was 0.35 in the normotensive group, 0.59 in the WCH group, and 0.65 in the group with ambulatory hypertension. In a multivariate analysis, the adjusted hazard ratio for stroke was 1.15 (95% confidence interval [CI], 0.61 to 2.16) in the WCH group (
P
=0.66) and 2.01 (95% CI, 1.31 to 3.08) in the ambulatory hypertension group (
P
=0.001) compared with the normotensive group. After the sixth year of follow-up, the incidence of stroke tended to increase in the WCH group, and the corresponding hazard curve crossed that of the ambulatory hypertension group by the ninth year of follow-up. In conclusion, WCH was not associated with a definitely increased risk of stroke during the total follow-up period. However, WCH might not be a benign condition for stroke in the long term.
Ambulatory Blood Pressure and 10-Year Risk of Cardiovascular and Noncardiovascular Mortality
Authors: Kikuya Masahiro , Ohkubo Takayoshi , Asayama Kei , Metoki Hirohito , Obara Taku , Saito Shin , Hashimoto Junichiro , Totsune Kazuhito , Hoshi Haruhisa , Satoh Hiroshi , Imai Yutaka
Published: January 2005

The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure. Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged ≥40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure.