bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of cellular telephones and brain tumour risk in urban and rural areas
Authors: Hardell L , Carlberg M , Hansson Mild K
Published: May 2005

Aims:To investigate the association between the use of cellular or cordless telephones and the risk for brain tumours in different geographical areas, urban and rural.

Methods:Patients aged 20–80 years, living in the middle part of Sweden, and diagnosed between 1 January 1997 and 30 June 2000 were included. One control matched for sex and age in five year age groups was selected for each case. Use of different phone types was assessed by a questionnaire.

Results:The number of participating cases was 1429; there were 1470 controls. An effect of rural living was most pronounced for digital cellular telephones. Living in rural areas yielded an odds ratio (OR) of 1.4 (95% CI 0.98 to 2.0), increasing to 3.2 (95% CI 1.2 to 8.4) with >5 year latency time for digital phones. The corresponding ORs for living in urban areas were 0.9 (95% CI 0.8 to 1.2) and 0.9 (95% CI 0.6 to 1.4), respectively. This effect was most obvious for malignant brain tumours.

Conclusion:In future studies, place of residence should be considered in assessment of exposure to microwaves from cellular telephones, although the results in this study must be interpreted with caution due to low numbers in some of the calculations.
ORIENTATIONS IN LEGENDRIAN CONTACT HOMOLOGY AND EXACT LAGRANGIAN IMMERSIONS
Authors: EKHOLM TOBIAS , ETNYRE JOHN , SULLIVAN MICHAEL
Published: May 2005

We show how to orient moduli spaces of holomorphic disks with boundary on an exact Lagrangian immersion of a spin manifold into complex n-space in a coherent manner. This allows us to lift the coefficients of the contact homology of Legendrian spin submanifolds of standard contact (2n + 1)-space from ℤ2 to ℤ. We demonstrate how the ℤ-lift provides a more refined invariant of Legendrian isotopy. We also apply contact homology to produce lower bounds on double points of certain exact Lagrangian immersions into ℂn and again including orientations strengthens the results. More precisely, we prove that the number of double points of an exact Lagrangian immersion of a closed manifold M whose associated Legendrian embedding has good DGA is at least half of the dimension of the homology of M with coefficients in an arbitrary field if M is spin and in ℤ2 otherwise.
A COUNTEREXAMPLE TO LIPSMAN'S CONJECTURE
Authors: YOSHINO TARO
Published: May 2005

We consider the affine action of a nilpotent Lie group on ℝn. Lipsman (1995) conjectured that such an action is proper in the sense of Palais if and only if the action is (CI) in the sense of Kobayashi. The present paper gives a counterexample to Lipsman's conjecture for n ≥ 5.
C*-ALGEBRAS GENERATED BY A PROJECTION AND THE REDUCED GROUP C*-ALGEBRAS ${C^*_r\Bbb Z*\Bbb Z_n}$ AND ${C^*_r\Bbb Z_m*\Bbb Z_n}$
Authors: ZHANG SHUANG
Published: May 2005

Let Γ=ℤm * ℤn or ℤ * ℤn, and let Γ(h) be the subtree consisting of all reduced words starting with any reduced word h ∈ Γ\{e}. We prove that the C*-algebra [Formula: see text] generated by [Formula: see text] and the projection Ph onto the subspace ℓ2(Γ(h)) has a unique nontrivial closed ideal ℐ, ℐ is *-isomorphic to [Formula: see text], and the quotient algebra [Formula: see text] is *-isomorphic to either [Formula: see text] or [Formula: see text] depending on the last letter of h. We also prove that [Formula: see text] is a purely infinite, simple C*-algebra if the last letter of h is a generator of ℤ, and that [Formula: see text] has a unique nontrivial closed ideal [Formula: see text] if the last letter of h is a generator of ℤn; furthermore, [Formula: see text] is *-isomorphic to [Formula: see text] and [Formula: see text] is again a purely infinite, simple C*-algebra. As consequences, all the C*-algebras above have real rank zero, and [Formula: see text] is nuclear for any h ≠ e.
AN EFFICIENT EXPLORATION OF MULTIMEDIA ARCHITECTURE USING WEIGHTED PARAMETER DEPENDENCY AND SAMPLED-DATA SIMULATION
Authors: KIM YEONG GEOL , KIM TAG GON
Published: May 2005

This paper proposes a system-level design methodology for efficient exploration of parameterized multimedia architecture. The purpose is to find a near-optimal configuration, as far as possible, without performing exhaustive analysis of the design space. This is done through synergistic integration of two independent methodologies, first of which is the multi-stage dynamic optimization based on parameters clustering and sparsing, while the second one being a quick performance estimation through sampled-data simulation of target multimedia application. The experimental results with mediabench show speedup ranging from 186.4 to 339.8, while the corresponding error-to-global optimum ranges from 14.8% to 16.4%.
A UNIFIED ENVIRONMENT TO ASSESS IMAGE QUALITY IN VIDEO PROCESSING
Authors: CANTIN M.-A. , REGIMBAL S. , CATUDAL S. , SAVARIA Y.
Published: May 2005

A new unified environment to analyze hardware implementations of video processing and noise reduction algorithms is proposed and analyzed. Based on an automatic word-length determination tool, it evaluates the implementation costs required to reach a given quality target by performing several tests with noisy images at different noise levels. The unified environment uses a universal image quality index to compute the effect of finite precision on image quality. Also, this unified environment has the capacity to distribute the analysis task over a computer network in order to reduce the required processing latency. This unified environment helps to determine which algorithm requires the lowest implementation cost. Furthermore, the unified environment is useful to explore multiple hardware architectures that can be used to implement a given noise reduction algorithm.
A SPATIAL-TEMPORAL ANALYSIS ON PATTERN FORMATION AROUND WATER POINTS IN A SEMI-ARID RANGELAND SYSTEM
Authors: WITTEN G. Q. , RICHARDSON F. D. , SHENKER N.
Published: May 2005

The spatial grazing pattern of goats around a water point on an arid and semi-arid rangeland system in the Karoo in South Africa was modeled. A dynamic automata model was developed by subdividing a spatial area into subunits called cells and where the dynamics of each cell depends on its present state, the state of its neighbors and external factors such as rainfall. By using a dynamic automata model, the long-term influences on the changes in vegetation composition of two species, namely woody perennials and galenia africana, are investigated.

The model relates a preference equation, which is a combination of two parameters, forage density and distance to a water point, to the total amount of time spent by each animal within a particular cell in a year. The model provides evidence that the total number of animals grazing an area, the number of water points in the system and the weighting factors associated with the preference equation, influence the extent of degradation of the area.
DYNAMICS OF INHOMOGENEOUS POPULATIONS AND GLOBAL DEMOGRAPHY MODELS
Authors: KAREV GEORGY P.
Published: May 2005

The dynamic theory of inhomogeneous populations developed during the last decade predicts several essential new dynamic regimes applicable even to the well-known, simple population models. We show that, in an inhomogeneous population with a distributed reproduction coefficient, the entire initial distribution of the coefficient should be used to investigate real population dynamics. In the general case, neither the average rate of growth nor the variance or any finite number of moments of the initial distribution is sufficient to predict the overall population growth. We developed methods for solving the heterogeneous models and explored the dynamics of the total population size together with the reproduction coefficient distribution. We show that, typically, there exists a phase of "hyper-exponential" growth that precedes the well-known exponential phase of population growth in a free regime.

The developed formalism is applied to models of global demography and the problem of "population explosion" predicted by the known hyperbolic formula of world population growth. We prove here that the hyperbolic formula presents an exact solution to the Malthus model with an exponentially distributed reproduction coefficient and that "population explosion" is a corollary of certain implicit unrealistic assumptions. Alternative models of world population growth are derived; they show a notable phenomenon, a transition from protracted hyperbolical growth (the phase of "hyper-exponential" development) to the brief transitional phase of exponential growth and, subsequently, to stabilization. The model solutions are consistent with real data and produce relatively accurate forecasts.
THRESHOLD AND STABILITY RESULTS FOR AN SIRS EPIDEMIC MODEL WITH A GENERAL PERIODIC VACCINATION STRATEGY
Authors: MONEIM I. A. , GREENHALGH D.
Published: May 2005

An SIRS epidemic model with general periodic vaccination strategy is analyzed. This periodic vaccination strategy is discussed first for an SIRS model with seasonal variation in the contact rate of period T = 1 year. We start with the case where the vaccination strategy and the contact rate have the same period and then discuss the case where the period of the vaccination strategy is LT, where L is an integer. We investigate whether a periodic vaccination strategy may force the epidemic dynamics to have periodic behavior. We prove that our SIRS model has a unique periodic disease free solution (DFS) whose period is the same as that of the vaccination strategy, which is globally asymptotically stable when the basic reproductive number R0is less than or equal to one in value. When R0> 1, we prove that there exists a non-trivial periodic solution of period the same as that of the vaccination strategy. Some persistence results are also discussed. Threshold conditions for these periodic vaccination strategies to ensure that R0≤ 1 are derived.
CONTROLLING INTRACELLULAR CALCIUM OSCILLATIONS AND WAVES
Authors: PUEBLA HECTOR
Published: May 2005

Biological systems perform complex signal transduction at the cellular level. Intracellular calcium ( Ca 2+) plays a significant role in signal transduction from receptors at the cell membrane to enzymes and genes controlling the complex biochemical network of the cell. Intracellular Ca 2+ shows a rich behavior of nonlinear dynamics including excitability, oscillations and nonlinear waves. In this work, a feedback control approach is introduced to control intracellular calcium dynamics of both well-mixed cell (calcium oscillations) and distributed (nonlinear waves) parameter models using an external control input that causes an influx of Ca 2+ to the signaling calcium pathway. Numerical simulations shows the effectiveness of the feedback control laws proposed.
A MATHEMATICAL MODEL FOR SPATIALLY EXPANDING INFECTED AREA OF EPIDEMICS TRANSMITTED THROUGH HETEROGENEOUSLY DISTRIBUTED SUSCEPTIBLE UNITS
Authors: KOSHIBA SHINKO , SENO HIROMI
Published: May 2005

Little is known about the effect of environmental heterogeneity on the spatial expansion of epidemics. In this work, to focus on the question of how the extent of epidemic damage depends on the spatial distribution of susceptible units, we develop a mathematical model with a simple stochastic process, and analyze it. We assume that the unit of infection is immobile, as town, plant, etc. and classify the units into three classes: susceptible, infective and recovered. We consider the range expanded by infected units, the infected rangeR, assuming a certain generalized relation between R and the total number of infected units k, making use of an index, a sort of fractal dimension, to characterize the spatial distribution of infected units. From the results of our modeling analysis, we show that the expected velocity of spatial expansion of infected range is significantly affected by the fractal nature of spatial distribution of immobile susceptible units, and is temporally variable. When the infection finally terminates at a moment, the infected range at the moment is closely related to the nature of spatial distribution of immobile susceptible units, which is explicitly demonstrated in our analysis.
Hypercube Network Fault Tolerance: A Probabilistic Approach
Authors: CHEN JIANER , KANJ IYAD A. , WANG GUOJUN
Published: May 2005

Extensive experiments and experience have shown that the well-known hypercube networks are highly fault tolerant. What is frustrating is that it seems very difficult to properly formulate and formally prove this important fact, despite extensive research efforts in the past two decades. Most proposed fault tolerance models for hypercube networks are only able to characterize very rare extreme situations thus significantly underestimating the fault tolerance power of hypercube networks, while for more realistic fault tolerance models, the analysis becomes much more complicated. In this paper, we develop new techniques that enable us to analyze a more realistic fault tolerance model and derive lower bounds for the probability of hypercube network fault tolerance in terms of node failure probability. Our results are both theoretically significant and practically important. From the theoretical point of view, our method offers very general and powerful techniques for formally proving lower bounds on the probability of network connectivity, while from the practical point of view, our results provide formally proven and precisely given upper bounds on node failure probabilities for manufacturers to achieve a desired probability for network connectivity. Our techniques are also useful and powerful for analysis of the performance of routing algorithms, and applicable to the study of other hierarchical network structures and to other network communication problems.
Wide Diameter of Möbius Cubes
Authors: Xu Jun-Ming , Deng Zhi-Guo
Published: May 2005

The Möbius cube is a variant of the hypercube and has better performance than the hypercube with the same number of links and processors. This paper shows that the wide diameter of the Möbius cube is at most [Formula: see text], about one half of the same dimensional hypercube's.
CLINICAL SIMULATION OF OGTT GLUCOSE RESPONSE MODEL FOR DIAGNOSIS OF DIABETIC PATIENT
Authors: GHISTA DHANJOO N. , CHUA PATRICK S. K. , AULIA ANDY UTAMA , YEO PETER L. P.
Published: May 2005

Diagnosis of diabetes is usually achieved by obtaining a single reading of blood-glucose concentration value from the Oral Glucose Tolerance Test (OGTT). However, the result itself is inadequate in providing insight into the glucose-regulatory etiology of diabetes disease disorder, which is important for treatment purposes. The objective of this project was to conduct clinical simulation and parametric identification of OGTT model for diagnosis of diabetic patient, so as to classify diabetic or at-risk patients into different categories, depending on the nature of their blood-glucose tolerance response to oral injestion of a bolus of glucose. In other words, the patient classification depends on how the blood-glucose concentration varies with time; i.e. how much does it peak, how long does it takes to reach its peak value, how fast does it return to the fasting value, etc. during the oral glucose tolerance test.

To represent this blood-glucose concentration [y(t)] regulatory dynamics, the model selected is a second-order differential equation, [Formula: see text] of blood-glucose concentration response to a bolus of ingested glucose Gδ(t). This model was then applied to the test subjects by making the model solution-expression for y(t) match the monitored clinical data of blood-glucose concentration at different time intervals, through clinical simulation and parametric identification. The solutions obtained from the model to fit the clinical data were different for normal and diabetic test subjects. The clinical data of "normal" subjects could be simulated by means of an under-damped solution of the model, as: y(t) = (G/ω)e-ωt sin ωt. The data of "diabetic" patients needed to be simulated by means of an over-damped solution of the model, as: y(t) = (G/ω)e-At sin hωt, where G represents the magnitude of the impulse input Gδ(t) to the model (in gms of glucose per litre of blood pool volume), ω is the damped oscillatory frequency of the model, wn is the natural frequency of the system and [Formula: see text].

In order to facilitate differential diagnosis, we developed a non-dimensional diabetic index (DI) expressed as: [Ay max Td/GT max ]. This index can be used to facilitate the diagnosis of diabetes as well as for assessing the risk to becoming diabetic.
DIFFERENTIAL EFFECTS OF SHEAR STRESS ON THE EXPRESSIONS OF ICAM-1 AND VCAM-1 INDUCED BY TNF-α IN ENDOTHELIAL CELLS
Authors: CHIU JENG-JIANN , LEE PEI-LING , USAMI SHUNICHI , CHIEN SHU
Published: May 2005

Vascular endothelial cells (ECs) are subjected to shear stress and cytokine stimulation. We studied the interplay between shear stress and cytokine in modulating the expression of adhesion molecule genes and the adhesive function of ECs. Shear stress (20 dynes/cm2) was applied to ECs prior to or following the addition of tumor necrosis factor (TNF)-α. Shear stress increased the TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-α-induced expression of vascular adhesion molecule-1 (VCAM-1). The TNF-α-induced increase in EC adhesiveness for monocytic THP-1 cells was reduced by shear stress. After 24-h pre-shearing followed by 1 h of static incubation, the effect of pre-shearing on TNF-α-induced ICAM-1 mRNA expression vanished. The recovery of the TNF-α-induced VCAM-1 mRNA expression following pre-shearing, however, required a static incubation time of >6 h (completely recovery at 24 h). Pre- and post-shearing caused a reduction in the nuclear factor (NF)-κB-DNA binding activity induced by TNF-α in the EC nucleus. Our findings suggest that shear stress plays differential roles in modulating the TNF-α-induced EC expressions of ICAM-1 and VCAM-1 genes, which serve similar functions in vascular biology.
PERFORMANCE CHARACTERIZATION AND CFD ANALYSIS OF AN AXIAL BLOOD PUMP
Authors: CHAN W. K. , WONG Y. W. , KOH S. Y. , CHONG V.
Published: May 2005

This paper describes the performance characterization of an axial blood pump that is developed in our laboratory. Using computational fluid dynamics (CFD), regions of flow separation and high shear stress were identified since they are of concern in the development of cardiac assist devices. CFD is an efficient and cost effective tool in assisting the designer to reduce the number of experimental trials needed. Preliminary CFD studies showed the existence of substantial backflow in the impeller passage. The impeller geometry was improved using CFD modeling. Regions of flow separation were eliminated while regions of scalar stress of up to 150 Pa were observed near to the impeller tip. The final prototype can deliver a flow rate of 5 L/min at a pressure head of 14 kPa when operating at a speed of 10,000 rpm. The model was fabricated using rapid prototyping techniques and performance characterization of the pump has demonstrated that the CFD prediction of the pump performance curve and the pressure developed along the impeller agrees reasonably well with experimental results.
Comparing biology majors from large lecture classes with TA-facilitated laboratories to those from small lecture classes with faculty-facilitated laboratories
Authors: Goodman Barbara E. , Koster Karen L. , Redinius Patrick L.
Published: May 2005

The teaching faculty for this course sought to address their own concerns about the quality of student learning in an impersonal large lecture biology class for majors, the difficulties in getting to know each student by name, and difficulties in soliciting answers and reactions from the students during the lecture. Questions addressed by this study were, Do active-learning activities in a small and personal lecture setting enhance student learning more than active-learning activities in large impersonal lectures? and Are students more satisfied with an educational experience in a small and personal lecture setting? Based on faculty perceptions of how they best relate to their students, the prediction was that the students in the experimental group with small lecture classes and increased direct contact with the teaching faculty would learn physiological principles better than the students in the control group in the large impersonal lecture portion of the course. One of the laboratory sections of this large enrollment biology course was randomly selected to be taught with separate small lectures by the teaching faculty. In addition, the teaching faculty participated in the laboratory with these students during their experiments correlated with the lecture material. The students in both groups were compared by pre- and posttests of physiological principles, final course grades, and class satisfaction surveys.
Desensitization of the JAK2/STAT5 GH signaling pathway associated with increased CIS protein content in liver of pregnant mice
Authors: Miquet Johanna G. , Sotelo Ana I. , Bartke Andrzej , Turyn Daniel
Published: May 2005

Chronic exposure to growth hormone (GH) was related to the desensitization of the JAK2/STAT5 signaling pathway in liver, as demonstrated in cells, female rats, and transgenic mice overexpressing GH. The cytokine-induced suppressor (CIS) is considered a major mediator of this desensitization. Pregnancy is accompanied by an increment in GH circulating levels, which were reported to be associated with hepatic GH resistance, although the molecular mechanisms involved in this resistance are not clearly elucidated. We thus evaluated the JAK2/STAT5b signaling pathway and its regulation by the suppressors of cytokine signaling (SOCS)/CIS family and the JAK2-interacting protein SH2-Bβ in pregnant mouse liver, a model with physiological prolonged exposure to high GH levels. Basal tyrosyl phosphorylation levels of JAK2 and STAT5b in pregnant mice were similar to values obtained for virgin animals, in spite of the important increment of GH they exhibit. Moreover, these signaling mediators were not phosphorylated upon GH stimulation in pregnant mice. A 3.3-fold increase of CIS protein content was found for pregnant mice, whereas the abundance of the other SOCS proteins analyzed and SH2-Bβ did not significantly change compared with virgin animals. The desensitization of the JAK2/STAT5b GH signaling pathway observed in pregnant mice would then be mainly related to increased CIS levels rather than to the other regulatory proteins examined.
Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice
Authors: Hull Rebecca L. , Watts Melissah R. , Kodama Keiichi , Shen Zhen-ping , Utzschneider Kristina M. , Carr Darcy B. , Vidal Josep , Kahn Steven E.
Published: May 2005

Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and β-cell dysfunction. Islet amyloid is associated with reduced β-cell mass and function and develops in the majority of our C57BL/6J × DBA/2J (F1) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL/6J (BL6) and DBA/2J (DBA2), to islet amyloid formation, we studied male hIAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL/6J × DBA/2J F1mice ( n = 17) on a 9% (wt/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, F1: 76%, DBA2: 100%). However, the prevalence (%amyloid-positive islets; BL6: 14 ± 3%, F1: 44 ± 8%, DBA2: 49 ± 9%, P < 0.05) and severity (%islet area occupied by amyloid; BL6: 0.03 ± 0.01%, F1: 9.2 ± 2.9%, DBA2: 5.7 ± 2.3%, p ≤ 0.01) were significantly lower in BL6 than F1and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in F1( r2= 0.75, P < 0.001) and DBA2 ( r2= 0.87, P < 0.001) mice but not BL6 mice ( r2= 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA/2J genes (F1and DBA2 mice) being more susceptible to amyloid deposition that replaces β-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease.
Interleukin-1β and tumor necrosis factor-α mediation of endotoxin action on growth hormone
Authors: Daniel J. A. , Elsasser T. H. , Martínez A. , Steele B. , Whitlock B. K. , Sartin J. L.
Published: May 2005

In humans and sheep, endotoxin (LPS) administration results in increased growth hormone (GH) concentrations. To determine the role of cytokines in the effect of LPS on GH, sheep were challenged with IL-1β or TNF-α. GH data were compared with results with LH, where the major effects of LPS are known to act via the hypothalamus. Intracerebroventricular (icv) administration of IL-1β or TNF-α did not alter plasma concentrations of GH. Endotoxin was then administered intravenously (iv) in combination with icv injection of IL-1 receptor antagonist (IL-1RA), TNF antagonist (sTNF-R1), or saline. Administration of LPS increased GH ( P < 0.0001), although coadministration of IL-1ra or sTNF-R1 icv did not alter GH response to LPS. In contrast, plasma concentrations of LH were profoundly inhibited by icv administration of either cytokine ( P < 0.03), but the LH response to LPS was not altered by cytokine antagonists. Intravenous administration of either IL-1β or TNF-α increased plasma concentrations of GH ( P < 0.0001). Administration of IL-1RA and sTNF-R1 iv prevented LPS-induced increases in GH. Although LH was suppressed by high iv doses of IL-1β ( P = 0.0063), the antagonists did not alter the LH response to LPS. To determine whether LPS might directly activate GH release, confocal microscopy revealed colocalization of CD14, the LPS receptor, with GH and, to a lesser extent, LH and some prolactin (PRL)-containing cells, but not ACTH or TSH. These data are consistent with the effects of LPS on GH secretion originating through peripheral cytokine presentation to the pituitary, as well as a potential to act directly on selective populations of pituitary cells via CD14.
Leptin resistance extends to the coronary vasculature in prediabetic dogs and provides a protective adaptation against endothelial dysfunction
Authors: Knudson Jarrod D. , Dincer Ü. Deniz , Dick Gregory M. , Shibata Haruki , Akahane Rie , Saito Masayuki , Tune Johnathan D.
Published: May 2005

Hyperleptinemia, associated with prediabetes, is an independent risk factor for coronary artery disease and a mediator of coronary endothelial dysfunction. We previously demonstrated that acutely raising the leptin concentration to levels comparable with those observed in human obesity significantly attenuates coronary dilation/relaxation to acetylcholine (ACh) both in vivo in anesthetized dogs and in vitro in isolated canine coronary rings. Accordingly, the purpose of this investigation was to extend these studies to a model of prediabetes with chronic hyperleptinemia. In the present investigation, experiments were conducted on control and high-fat-fed dogs. High-fat feeding caused a significant increase (131%) in plasma leptin concentration. Furthermore, in high-fat-fed dogs, exogenous leptin did not significantly alter vascular responses to ACh in vivo or in vitro. Coronary vasodilator responses to ACh (0.3–30.0 μg/min) and sodium nitroprusside (1.0–100.0 μg/min) were not significantly different from those observed in control dogs. Also, high-fat feeding did not induce a switch to an endothelium-derived hyperpolarizing factor as a major mediator of muscarinic coronary vasodilation, because dilation to ACh was abolished by combined pretreatment with Nω-nitro-l-arginine methyl ester (150 μg/min ic) and indomethacin (10 mg/kg iv). Quantitative, real-time PCR revealed no significant difference in coronary artery leptin receptor gene expression between control and high-fat-fed dogs. In conclusion, high-fat feeding induces resistance to the coronary vascular effects of leptin, and this represents an early protective adaptation against endothelial dysfunction. The resistance is not due to altered endothelium-dependent or -independent coronary dilation, increased endothelium-derived hyperpolarizing factor, or changes in coronary leptin receptor mRNA levels.
Effect of mechanical stretch on HIF-1α and MMP-2 expression in capillaries isolated from overloaded skeletal muscles: laser capture microdissection study
Authors: Milkiewicz Malgorzata , Haas Tara L.
Published: May 2005

Under physiological nonhypoxic conditions, angiogenesis can be driven by mechanical forces. However, because of the limitations of the specific gene expression analysis of microvessels from in vivo experiments, the mechanisms regulating the coordinated expression of angiogenic factors implicated in the process remain intangible. In this study, the technique of laser capture microdissection (LCM) was adapted for the study of angiogenesis in skeletal muscles. With a combination of LCM and real-time quantitative PCR it was demonstrated that capillary endothelial cells produce matrix metalloproteinase (MMP)-2 and that mechanical stretch of capillaries within muscle tissue markedly increases MMP-2 mRNA (2.5-fold increase vs. control; P < 0.05). In addition, we showed that transcription factor hypoxia-inducible factor (HIF)-1α expression was 13.5-fold higher in capillaries subjected to stretch compared with controls ( P < 0.05). These findings demonstrate the feasibility of this approach to study angiogenic gene regulation and provide novel evidence of HIF-1α induction in stretched capillary endothelial cells.
Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats
Authors: Matsumoto Takayuki , Wakabayashi Kentaro , Kobayashi Tsuneo , Kamata Katsuo
Published: May 2005

To assess the functional change in adenylyl cyclases (AC) associated with the diabetic state, we investigated AC-mediated relaxations and cAMP production in mesenteric arteries from rats with streptozotocin (STZ)-induced diabetes. The relaxations induced by the water-soluble forskolin (FSK) analog NKH477, which is a putative AC5 activator, but not by the β-adrenoceptor agonist isoproterenol (Iso) and the AC activator FSK, were reduced in intact diabetic mesenteric artery. In diabetic rats, however, Iso-, FSK-, and NKH477-induced relaxations were attenuated in the presence of inhibitors of nitric oxide synthase and cyclooxygenase. To exclude the influence of phosphodiesterase (PDE), we also examined the relaxations induced by several AC activators in the presence of 3-isobutyl-1-methylxanthine (IBMX; a PDE inhibitor). Under these conditions, the relaxation induced by Iso was greatly impaired in STZ-diabetic rats. This Iso-induced relaxation was significantly attenuated by pretreatment with SQ-22536, an AC inhibitor, in mesenteric rings from age-matched controls but not in those from STZ-diabetic rats. Under the same conditions, the relaxations induced by FSK or NKH477 were impaired in STZ-diabetic rats. Neither FSK- nor A-23187 (a Ca2+ionophore)-induced cAMP production was significantly different between diabetics and controls. However, cAMP production induced by Iso or NKH477 was significantly impaired in diabetic mesenteric arteries. Expression of mRNAs and proteins for AC5/6 was lower in diabetic mesenteric arteries than in controls. These results suggest that AC-mediated relaxation is impaired in the STZ-diabetic rat mesenteric artery, perhaps reflecting a reduction in AC5/6 activity.
Effects of spironolactone and eprosartan on cardiac remodeling and angiotensin-converting enzyme isoforms in rats with experimental heart failure
Authors: Karram Tony , Abbasi Anan , Keidar Shlomo , Golomb Eliahu , Hochberg Irit , Winaver Joseph , Hoffman Aaron , Abassi Zaid
Published: May 2005

Angiotensin-converting enzyme (ACE)-2 is a newly described enzyme with antagonistic effects to those of the classical ACE (ACE-1). Both ANG II and aldosterone play an important role in the pathophysiology of congestive heart failure (CHF) and in the adverse cardiac remodeling during its development. In this study, we examined the effects of experimental CHF induced by an aortocaval fistula (ACF) and of its treatment with ANG II and aldosterone inhibitors on the relative levels of ACE-1 and ACE-2. We also compared the effects of spironolactone, an aldosterone antagonist, and eprosartan, an ANG II receptor antagonist, on heart hypertrophy and fibrosis in rats with ACF. Spironolactone (15 mg·kg−1·day−1ip, via minipump) or eprosartan (5 mg·kg−1·day−1ip, via minipump) was administered into rats with ACF for 14 and 28 days. Specific antibodies were used to determine the protein levels of myocardial ACE-1 and ACE-2. ACF increased the cardiac levels of ACE-1 and decreased those of ACE-2. Heart-to-body weight ratio significantly increased from 0.30 ± 0.004% in sham-operated controls to 0.50 ± 0.018% and 0.56 ± 0.044% ( P < 0.001) in rats with ACF, 2 and 4 wk after surgery, respectively, in association with increased plasma levels of aldosterone. The area occupied by collagen increased from 2.33 ± 0.27% to 6.85 ± 0.65% and 8.03 ± 0.93% ( P < 0.01), 2 and 4 wk after ACF, respectively. Both spironolactone and eprosartan decreased cardiac mass and collagen content and reversed the shift in ACE isoforms. ACF alters the ratio between ACE isoforms in a manner that increases local ANG II and aldosterone levels. Early treatment with both ANG II and aldosterone antagonists is effective in reducing this effect. Thus ACE isoform shift may represent an important component of the development of cardiac remodeling in response to hemodynamic overload, and its correction may contribute to the beneficial therapeutic effects of renin-angiotensin-aldosterone system inhibitors.
Superiority of combination of thiazide with angiotensin-converting enzyme inhibitor or AT1-receptor blocker over thiazide alone on renoprotection inl-NAME/SHR
Authors: Zhou Xiaoyan , Matavelli Luis C. , Ono Hidehiko , Frohlich Edward D.
Published: May 2005

The renal and glomerular dynamic effects of combining thiazide and angiotensin antagonists have not been reported. The present study was designed to examine the effects of hydrochlorothiazide (HCTZ) alone or in combination with an angiotensin-converting enzyme inhibitor or ANG II type 1-receptor blocker on renal hemodynamics, glomerular dynamics, renal function, and renal histopathology in the Nω-nitro-l-arginine methyl ester-treated spontaneously hypertensive rat (l-NAME/SHR) model. HCTZ (80 mg·kg−1·day−1) alone or in combination with enalapril (30 mg·kg−1·day−1) or losartan (30 mg·kg−1·day−1) or enalapril (15 mg·kg−1·day−1) plus losartan (15 mg·kg−1·day−1) was administered to l-NAME/SHR (5.0 ± 0.10 mg·kg−1·day−1) for 3 wk. Mean arterial pressure, total peripheral resistance, renal plasma flow, glomerular filtration rate, glomerular hydrostatic pressure, afferent and efferent glomerular arteriolar resistances, single nephron plasma flow, single nephron glomerular filtration rate, serum creatinine concentration, 24-h urinary protein excretion, and glomerular and arteriolar injury scores were determined. HCTZ reduced mean arterial pressure, total peripheral resistance, glomerular hydrostatic pressure, and afferent and efferent glomerular arteriolar resistances ( P < 0.05, at least) but slightly increased renal plasma flow and single nephron plasma flow associated with reduced serum creatinine concentration, urinary protein excretion, and arteriolar injury score compared with l-NAME/SHR control. However, the combination of enalapril and/or losartan with HCTZ markedly improved each of these functions. These results demonstrated minor benefits of HCTZ monotherapy and a marked superiority of its combination with enalapril and/or losartan over HCTZ monotherapy on renoprotection in l-NAME/SHR, thereby providing strong evidence of their clinical benefits for hypertensive patients with renal functional impairment.
Interactive effects of superoxide anion and nitric oxide on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension
Authors: Patterson Matthew E. , Mouton Cynthia R. , Mullins John J. , Mitchell Kenneth D.
Published: May 2005

Superoxide anion contributes to the pathogenesis of various forms of hypertension, but its role in the development of malignant hypertension remains unclear. The present study was performed to determine the influence of superoxide anion on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Malignant hypertension was induced in male Cyp1a1-Ren2 rats ( n = 6) through dietary administration of the aryl hydrocarbon, indole-3-carbinol (0.3%) for 7–9 days. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the superoxide dismutase mimetic tempol (100 μmol/h). Basal MAP and renal vascular resistance (RVR) were elevated in rats induced with indole-3-carbinol compared with noninduced rats ( n = 5) (184 ± 4 vs. 127 ± 3 mmHg, P < 0.01, and 29 ± 2 vs. 21 ± 1 mmHg·ml−1·min·g, P < 0.01, respectively). Hypertensive rats had elevated excretion of urinary 8-isoprostane compared with normotensive rats (41 ± 4 vs. 13 ± 6 pg·min−1·g−1, P < 0.01). There were no differences in renal plasma flow and glomerular filtration rate between groups. Systemic administration of tempol decreased MAP (184 ± 4 to 151 ± 4 mmHg, P < 0.01) and RVR (29 ± 2 to 25 ± 2 mmHg·ml−1·min·g, P < 0.05) in hypertensive but not in normotensive Cyp1a1-Ren2 rats. In addition, tempol administration decreased urinary excretion of 8-isoprostane (41 ± 4 to 25 ± 4 pg·min−1·g−1, P < 0.05). Renal plasma flow and glomerular filtration rate remained unaltered during tempol administration in both groups. The administration of the nitric oxide synthase inhibitor nitro-l-arginine attenuated the decrease in MAP and RVR in response to tempol. These findings indicate that superoxide anion contributes to the elevated RVR and increased arterial blood pressure, by a mechanism that is at least in part nitric oxide dependent, in Cyp1a1-Ren2 rats with malignant hypertension.
High NaCl increases TonEBP/OREBP mRNA and protein by stabilizing its mRNA
Authors: Cai Qi , Ferraris Joan D. , Burg Maurice B.
Published: May 2005

Hypertonicity increases mRNA and protein abundance of the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), contributing to increased transcription of downstream osmoprotective genes. Previously, this was attributed to increased transcription of TonEBP/OREBP because no change was found in its mRNA stability. However, there is no direct evidence for increased transcription, and the 3′-untranslated region (UTR) of TonEBP/OREBP contains numerous adenylate/uridylate-rich elements, which can modulate RNA stability. Therefore, we have reinvestigated the effect of hypertonicity on TonEBP/OREBP mRNA stability. We find that, in mouse inner medullary collecting duct cells, raising osmolality from 300 to 500 mosmol/kgH2O by adding NaCl increases TonEBP/OREBP mRNA to a peak of 2.3-fold after 4 h, followed by a decline. TonEBP/OREBP protein increases to a sustained peak of 3.0-fold at 8 h. To determine the stability of TonEBP/OREBP mRNA, we measured the rate of its decrease after inhibiting transcription with actinomycin D, finding that it is stabilized for 6 h after addition of NaCl. This stabilization is sufficient to explain the increase in mRNA without any change in transcription. To investigate how hypertonicity stabilizes TonEBP/OREBP mRNA, we tested luciferase reporters containing parts of the TonEBP/OREBP mRNA UTR. Inclusion of both the 5′- and 3′-UTR increases reporter activity, consistent with mRNA stabilization. Surprisingly, however, it is the 5′-UTR that stabilizes; the 3′-UTR, by itself, decreases reporter activity. We concluded that 1) hypertonicity stabilizes TonEBP/OREBP mRNA, contributing to its increase, and 2) stabilization depends on the presence of the 5′-UTR.
Gene expression analysis of Tek/Tie2 signaling
Authors: Chen Stephen H. , Babichev Yael , Rodrigues Natalie , Voskas Daniel , Ling Ling , Nguyen Vicky P. K. H. , Dumont Daniel J.
Published: May 2005

The elaboration of the vasculature during embryonic development involves restructuring of the early vessels into a more complex vascular network. Of particular importance to this vascular remodeling process is the requirement of the Tek/Tie2 receptor tyrosine kinase. Mouse gene-targeting studies have shown that the Tie2-deficient embryos succumb to embryonic death at midgestation due to insufficient sprouting and remodeling of the primary capillary plexus. To identify the underlying genetic mechanisms regulating the process of vascular remodeling, transcriptomes modulated by Tie2 signaling were analyzed utilizing serial analysis of gene expression (SAGE). Two libraries were constructed and sequenced using embryonic day 8.5 yolk sac tissues from Tie2 wild-type and the Tie2-null littermates. After tag extraction, 45,689 and 45,275 SAGE tags were obtained for the Tie2 wild-type and Tie2-null libraries, respectively, yielding a total of 21,376 distinct tags. Close to 62% of the tags were uniquely annotated, whereas 10% of the total tags were unknown. Using semiquantitative PCR, the differential expression of eight genes was confirmed that included Elk3, an important angiogenic switch gene which was upregulated in the absence of Tie2 signaling. The results of this study provide valuable insight into the potential association between Tie2 signaling and other known angiogenic pathways as well as genes that might have novel functions in vascular remodeling.
Effects of Cold Preservation on the Lung Mechanical Properties in Rats
Authors: Ikeyama K. , Sakai H. , Omasa M. , Nakamura T. , Hamakawa H. , Fujinaga T. , Fukuse T. , Wada H.
Published: May 2005

In lung transplantation, cold preservation is an important process. However, the mechanical changes in the airway and tissue during cold preservation, especially before reperfusion, are unknown. To test the hypothesis that the mechanical changes in the airway and lung parenchyma start during cold preservation, we investigated the mechanical properties of the rat lung as a whole organ and in excised lung strips. In the 0 h group, the lungs were not preserved. In the 9 and 24 h group, the lungs were preserved for 9 and 24 h at 4°C. After preservation, we evaluated the static compliance (Csta) of the whole lung as obtained from the pressure volume curves (n = 5 in each group). Also, we measured the input impedance taken by a computer-controlled small-animal ventilator (n = 9 in each group). All data were analyzed using a homogeneous linear model, which includes airway resistance (Raw), tissue elastance (H), and tissue resistance (G). Hysteresivity (η) was calculated as G/H. Moreover, the tissue elasticity (Eqs) obtained from the quasi-static stress-strain curves was compared. There was no significant difference in Csta among the three groups. Raw was significantly lower in the 24 h group than in the 0 h group (p < 0.01). Eqs was significantly higher in the preserved groups than in the 0 h group (p < 0.01). These results demonstrated that the changes in the three mechanical properties of the airway and the tissue started within 9 h of preservation.
Evaluation of Tumour Vascularisation in Two Rat Sarcoma Models for Studying Isolated Lung Perfusion
Authors: Pan Youmin , Krueger T. , Tran Nam , Yan Hua , Ris H.-B. , McKee T.A.
Published: May 2005

Isolated cytostatic lung perfusion (ILP) is an attractive technique allowing delivery of a high-dose of cytostatic agents to the lungs while limiting systemic toxicity. In developing a rat model of ILP, we have analysed the effect of the route of tumour cell injection on the source of tumour vessels. Pulmonary sarcomas were established by injecting a sarcoma cell suspension either by the intravenous (i.v.) route or directly into the lung parenchyma. Ink perfusion through either pulmonary artery (PA) or bronchial arteries (BA) was performed and the characteristics of the tumour deposits defined. i.v. and direct injection methods induced pulmonary sarcoma nodules, with similar histological features. The intraparenchymal injection of tumour cells resulted in more reliable and reproducible tumour growth and was associated with a longer survival of the animals. i.v. injected tumours developed a PA-derived vascular tree whereas directly injected tumours developed a BA-derived vasculature.
The Expression of rac1 Pseudogene in Human Tissues and in Human Brain Tumors
Authors: Hwang S.L. , Chang J.H. , Cheng C.Y. , Howng S.L. , Sy W.D. , Lieu A.S. , Lin C.L. , Lee K.S. , Hong Y.R.
Published: May 2005

Background: Recent studies have demonstrated that Rac is a regulator of cell morphology and growth. Rac1 gene appears to have involvement in tumorigenesis and metastatic potential. In our previous study of rac1 gene in 45 human brain tumors, rac1 pseudogene was found. The rac1 pseudogene is an intronless pseudogene and has a similarity of 86% with rac1 nucleotide sequence. The rac1 pseudogene contains 579 nucleotides and only 46 amino acids can be translated. Little is known about the expression of rac1 pseudogene in human tissues or tumors. Materials and Methods: The expression of rac1 gene and rac1 pseudogene in different human tissues and brain tumors was investigated by the use of reverse transcriptase-polymerase chain reaction and Northern blotting. Results: The rac1 gene is apparently expressed in these 8 human tissues. The rac1 pseudogene is also apparently expressed in human tissues except for brain tissue. The overexpression of rac1 gene in brain tumors was 8% (2/25) and the overexpression of rac1 pseudogene was 76.9% (20/26). Only two astrocytomas had overexpression of rac1 gene, compared with normal brain tissues. The overexpression of rac1 pseudogene was 6 of 9 in meningiomas, 7 of 9 in astrocytomas, and 7 of 8 in pituitary adenomas. Conclusions: High frequency of overexpression of rac1 pseudogene was detected in the human brain tumors when compared with that expressed in the normal brain tissues. Our study suggested that the rac1 pseudogene may play an important role of the tumorigenesis of brain.