bluuebunny/crossref_metadata_2025 huggingface dataset:
Tests of a within-channel account of comodulation detection differences
Authors: Moore Brian C. J. , Borrill Stephen J.
Published: October 2002

The threshold for detecting a narrow-band noise signal in one or more masking noise bands is higher when the signal and masker bands have the same envelope (correlated condition) than when they have independent envelopes (uncorrelated condition). This comodulation detection difference (CDD) might be caused by perceptual grouping of the signal and masker bands when they are correlated. Alternatively, CDD may occur because, in the uncorrelated condition, the signal can be detected in the dips of the masker. A previous paper [S. J. Borrill and B. C. J. Moore, J. Acoust. Soc. Am. 111, 309–319 (2002)] described results and a model supporting a dip-listening explanation. The model predicted steeper psychometric functions for the correlated than for the uncorrelated condition, a prediction confirmed by experiment 1. In experiment 2, the width of the signal and masker bands was varied. The dip-listening model predicts a small decrease in CDD with increasing bandwidth, while an account based on perceptual grouping predicts a substantial decrease, as across-channel sensitivity to envelope disparity decreases with increasing envelope modulation rate. The CDD was independent of bandwidth. Experiment 3 showed no effect of masker–signal onset asynchrony on CDD, even though asynchrony should reduce perceptual grouping. An explanation of CDD is proposed based on the suppression that has been observed in cochlear mechanics and in the auditory nerve.
Micromechanical modeling of viscoelastic voided composites in the low-frequency approximation
Authors: Haberman Michael R. , Berthelot Yves H. , Jarzynski J. , Cherkaoui Mohammed
Published: October 2002

The self-consistent model of Cherkaoui et al. [J. Eng. Mater. Technol. 116, 274–278 (1994)] is used to compute the effective material moduli of a viscoelastic material containing coated spherical inclusions. Losses are taken into account by introducing the frequency-dependent, complex shear modulus of the viscoelastic matrix. Mode conversion appears through the localization tensors that govern the micromechanical behavior near the inclusions. The results are compared with the scattering model and the data of Baird et al. [J. Acoust. Soc. Am. 105, 1527–1538 (1999)]. The two models are in good agreement. the advantage of the self-consistent model is that it is applicable to the case of nonspherical inclusions embedded in anisotropic materials.
Compressional and torsional wave amplitudes in rods with periodic structures
Authors: Morales A. , Flores J. , Gutiérrez L. , Méndez-Sánchez R. A.
Published: October 2002

To measure and detect elastic waves in metallic rods a low-frequency electromagnetic-acoustic transducer has been developed. Frequencies range from a few hertz up to hundreds of kilohertz. With appropriate configuration of the transducer, compressional or torsional waves can be selectively excited or detected. Although the transducer can be used in many different situations, it has been tested and applied to a locally periodic rod, which consists of a finite number of unit cells. The measured wave amplitudes are compared with theoretical ones, obtained with the one-dimensional transfer matrix method, and excellent agreement is obtained.
Normal incidence reflection loss from a sandy sediment
Authors: Chotiros Nicholas P. , Lyons Anthony P. , Osler John , Pace Nicholas G.
Published: October 2002

Acoustic reflection loss at normal incidence from a sandy sediment, in the Biodola Gulf on the north side of the island of Elba, Italy, was measured in the frequency band 8–17 kHz, using a self-calibrating method. The water depth was approximately 11 m. The mean and standard deviation of the sand grain diameter were 2.25 (0.21 mm) and 0.6 φ, respectively. The reflection loss was measured using an acoustic intensity integral method, which is insensitive to roughness effects within the selected frequency band. The measured value of reflection loss was 11 dB, ±2 dB. The result is consistent with previous measurements in the published literature. The computed reflection loss for a flat interface between water and a uniform fluid or visco-elastic medium with the same properties is 8 dB, ±1 dB. The theoretical and experimental values do not significantly overlap, which leads to the conclusion that the visco-elastic model is inappropriate. The Biot model is suggested as a better alternative but more work is needed to ascertain the appropriate parameter values.
Effects of perceptual assmilation on the production of English vowels by native Japanese speakers
Authors: Nozawa Takeshi , Frieda Elaina M.
Published: October 2002

In our previous studies, it was found that English vowel contrasts that were difficult for Japanese speakers to discriminate were for the most part identified with the same Japanese vowels. This finding complies with one the Perceptual Assimilation Model (Best, 1995) postulates. The present study investigated how perceptual assimilation affects production of English vowels by Japanese speakers. Three experienced Japanese learners in Columbus, Ohio, and five inexperienced Japanese learners in Kobe, Japan produced English vowels, repeating after two different native speakers’ utterances. Each subject heard the same token twice in a different order, so they each produced four tokens of each English vowel. The results support what our previous studies have found, and show the effects of perception on production. The production of the vowels difficult to discriminate tended to be close to each other within subjects’ production vowel space. The production of the vowels identified as good exemplars of Japanese vowels were more stable than those identified as poor exemplars. Thus, the subjects /i/ tokens were almost always identified as /i/, whereas their /æ/ tokens were often identified as /ε/, /ɑ/, or /ʌ/. Experienced learners’ utterances were far more correctly identified.
Sea turtle auditory behavior
Authors: Lenhardt Martin
Published: October 2002

Little is known of sea turtles’ auditory behavior. Startles (neck contractions) were observed in 25 loggerheads (Caretta caretta) to tones from 35 to 1000 Hz, when the turtles were near the bottom of holding tanks at a depth of 1 meter. A composite audiogram revealed lowest thresholds in the 400–500 Hz range (106 dB SPL re 1 μm). Thresholds at 735 and 1000 Hz were 117 and 156 dB, respectively. Thresholds in the 100–200 Hz range were ∼124 dB, with lower frequencies being 10–12 dB higher. Tank diving behavior was elicited with 30 Hz at 164 dB. ABR thresholds to vibration clicks with peak energy at 500 Hz were 113 dB. Seismic air guns (Bolt 600) were employed in a large net enclosure. Turtles increased swimming speed for exposures in the 151–161 dB levels. Avoidance ∼175 dB was common in initial trials, before habituation. ABRs pre- and post-air gun exposures revealed TTS of more than 15 dB in one animal with recovery in 2 weeks. Air guns in depths >10 m may result in more energy in the low frequencies with unknown bioeffects. Turtle repelling with sound is possible and can be made practical (Lenhardt, US Patent No. 6388949).
Stronger Constraints on the Anthropogenic Indirect Aerosol Effect
Authors: Lohmann Ulrike , Lesins Glen
Published: October 2002

The anthropogenic indirect aerosol effects of modifying cloud albedo and cloud lifetime cannot be deduced from observations alone but require a modeling component. Here we validate a climate model, with and without indirect aerosol effects, by using satellite observations. The model agrees better with observations when both indirect aerosol effects are included. However, the simulated clouds are more susceptible to aerosols than the observed clouds from the POLDER satellite, thus overestimating the indirect aerosol effect. By taking the difference in susceptibilities into account, the global mean total anthropogenic aerosol effect is reduced from –1.4 to –0.85 watts per square meter.
Cell Dynamics During Somite Boundary Formation Revealed by Time-Lapse Analysis
Authors: Kulesa Paul M. , Fraser Scott E.
Published: October 2002

We follow somite segmentation in living chick embryos and find that the shaping process is not a simple periodic slicing of tissue blocks but a much more carefully choreographed separation in which the somite pulls apart from the segmental plate. Cells move across the presumptive somite boundary and violate gene expression boundaries thought to correlate with the site of the somite boundary. Similarly, cells do not appear to be preassigned to a given somite as they leave the node. The results offer a detailed picture of somite shaping and provide a spatiotemporal framework for linking gene expression with cell movements.
Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by β-Defensin 2
Authors: Biragyn Arya , Ruffini Pier Adelchi , Leifer Cynthia A. , Klyushnenkova Elena , Shakhov Alexander , Chertov Oleg , Shirakawa Aiko K. , Farber Joshua M. , Segal David M. , Oppenheim Joost J. , Kwak Larry W.
Published: October 2002

β-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine β-defensin 2 (mDF2β) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2β may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.
Independent Origins and Rapid Evolution of the Placenta in the Fish Genus
Poeciliopsis
Authors: Reznick David N. , Mateos Mariana , Springer Mark S.
Published: October 2002

The evolution of complex organs is a source of controversy because they require the contributions of many adaptations to function properly. We argue that placentas are complex, that they have evolved multiple times in
Poeciliopsis
, and that there are closely related sister taxa that have either no placentas or intermediate stages in the evolution of a placenta. Furthermore, placentas can evolve in 750,000 years or less, on the same time scale as suggested by theoretical calculations for the evolution of complex eyes. Independent origins of such complexity, accompanied by sister taxa that either lack or have intermediate stages in the evolution of the trait, present an opportunity to study the evolution of novelty and complexity from a comparative, evolutionary perspective.
Contribution of Human α-Defensin 1, 2, and 3 to the Anti-HIV-1 Activity of CD8 Antiviral Factor
Authors: Zhang Linqi , Yu Wenjie , He Tian , Yu Jian , Caffrey Rebecca E. , Dalmasso Enrique A. , Fu Siyu , Pham Thang , Mei Jianfeng , Ho Jaclyn J. , Zhang Wenyong , Lopez Peter , Ho David D.
Published: October 2002

It has been known since 1986 that CD8 T lymphocytes from certain HIV-1–infected individuals who are immunologically stable secrete a soluble factor, termed CAF, that suppresses HIV-1 replication. However, the identity of CAF remained elusive despite an extensive search. By means of a protein-chip technology, we identified a cluster of proteins that were secreted when CD8 T cells from long-term nonprogressors with HIV-1 infection were stimulated. These proteins were identified as α-defensin 1, 2, and 3 on the basis of specific antibody recognition and amino acid sequencing. CAF activity was eliminated or neutralized by an antibody specific for human α-defensins. Synthetic and purified preparations of α-defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that α-defensin 1, 2, and 3 collectively account for much of the anti–HIV-1 activity of CAF that is not attributable to β-chemokines.
Detection and Monitoring of Ongoing Aseismic Slip in the Tokai Region, Central Japan
Authors: Ozawa Shinzaburo , Murakami Makoto , Kaidzu Masaru , Tada Takashi , Sagiya Takeshi , Hatanaka Yuki , Yarai Hiroshi , Nishimura Takuya
Published: October 2002

Analysis of global positioning system data shows that the rate of crustal deformations in the Tokai region of Japan, a seismic gap area, changed over the past 18 months. Kalman filtering analysis shows aseismic slip on the plate boundary in the western Tokai region centered on Lake Hamana, adjacent to the anticipated Tokai earthquake source area. The cumulative moment magnitude reaches 6.7 in June 2002 with a relative slip increase northeast of Lake Haman from January 2002. An existence of aseismic slip in the western Tokai supports the hypothesis of a silent event as the cause of uplifting several days before the 1944 Tonankai earthquake.
Climate Change and Latitudinal Patterns of Intertidal Thermal Stress
Authors: Helmuth Brian , Harley Christopher D. G. , Halpin Patricia M. , O'Donnell Michael , Hofmann Gretchen E. , Blanchette Carol A.
Published: October 2002

The interaction of climate and the timing of low tides along the West Coast of the United States creates a complex mosaic of thermal environments, in which northern sites can be more thermally stressful than southern sites. Thus, climate change may not lead to a poleward shift in the distribution of intertidal organisms, as has been proposed, but instead will likely cause localized extinctions at a series of “hot spots.” Patterns of exposure to extreme climatic conditions are temporally variable, and tidal predictions suggest that in the next 3 to 5 years “hot spots” are likely to appear at several northern sites.
A Transparent Foundation?
Authors: Gorman Michael John
Published: October 2002

The Glass Bathyscaphe
. How Glass Changed the World. Alan Macfarlane and Gerry Martin. Profile, London, 2002. 267 pp. £15. ISBN 186-197-400-0.

Glass
. A World History. University of Chicago Press, Chicago, 2002. 267 pp. $27.50 ISBN 0-226-50028-4.

In this account for a general audience, the authors argue that the scientific advances that transformed the world between the 13th and 17th centuries all occurred in western Europe because the glass technologies that developed there provided crucial new instruments such as microscopes, telescopes, barometers, thermometers, vacuum flasks, and retorts.
Effect of Pyruvate Carboxylase Overexpression on the Physiology of
Corynebacterium glutamicum
Authors: Koffas Mattheos A. G. , Jung Gyoo Yeol , Aon Juan C. , Stephanopoulos Gregory
Published: October 2002

Pyruvate carboxylase was recently sequenced in
Corynebacterium glutamicum
and shown to play an important role of anaplerosis in the central carbon metabolism and amino acid synthesis of these bacteria. In this study we investigate the effect of the overexpression of the gene for pyruvate carboxylase (
pyc
) on the physiology of
C. glutamicum
ATCC 21253 and ATCC 21799 grown on defined media with two different carbon sources, glucose and lactate. In general, the physiological effects of
pyc
overexpression in
Corynebacteria
depend on the genetic background of the particular strain studied and are determined to a large extent by the interplay between pyruvate carboxylase and aspartate kinase activities. If the pyruvate carboxylase activity is not properly matched by the aspartate kinase activity,
pyc
overexpression results in growth enhancement instead of greater lysine production, despite its central role in anaplerosis and aspartic acid biosynthesis. Aspartate kinase regulation by lysine and threonine, pyruvate carboxylase inhibition by aspartate (shown in this study using permeabilized cells), as well as well-established activation of pyruvate carboxylase by lactate and acetyl coenzyme A are the key factors in determining the effect of
pyc
overexpression on
Corynebacteria
physiology.
TUNNELING PROPERTIES BETWEEN YBa2Cu3O7-d AND Ba1-xKxBiO3 THIN FILMS
Authors: DEMIREL ALI IHSAN
Published: October 2002

In this study, a contact between YBa 2 Cu 3 O 7-d thin film and Ba 1-x K x BiO 3 thin film has been fabricated. The typical I–V characteristics of tunneling are shown in the contact to have different superconducting energy gaps. According to the I–V characteristics, the superconducting energy gaps, 2Δ, are calculated as 1.5 meV and 3 meV for YBa 2 Cu 3 O 7-d and for Ba 1-x K x BiO 3, respectively, along the c-axis. The contact boundary between these superconducting thin films shows a boundary Josephson junction with tunneling barrier properties.
FOUR-MODE EPR CONTINUOUS-VARIABLE ENTANGLED STATE AND ITS GENERATION
Authors: FAN HONGYI , LIANG XIANTING , CHEN JUNHUA
Published: October 2002

Based on Einstein, Podolsky and Rosen (EPR) quantum entanglement, we construct a new kind of four-mode entangled states of continuous variables in Fock space and examine its complete property and partly non-orthonormal property. A set-up of one beamsplitter and two polarizers can generate such a four-mode entangled state. The discussion can also be extended to constructing more particles' entangled states.
Central Ghrelin Modulates Sympathetic Activity in Conscious Rabbits
Authors: Matsumura Kiyoshi , Tsuchihashi Takuya , Fujii Koji , Abe Isao , Iida Mitsuo
Published: October 2002

Ghrelin is an orexigenic peptide originally isolated from the stomach. Intravenous administration of ghrelin has been shown to elicit a decrease in arterial pressure without a significant change in heart rate (HR), suggesting that ghrelin may act on the central nervous system to modulate sympathetic activity. The aim of the present study was to determine the central effects of ghrelin on cardiovascular and sympathetic responses in conscious rabbits. Intravenous injection of ghrelin elicited dose-related decreases in arterial pressure and HR, without a significant change in renal sympathetic nerve activity. On the other hand, intracerebroventricular injection of 1 nmol of ghrelin decreased arterial pressure, HR, and renal sympathetic nerve activity. Peak depressor or sympathoinhibitory responses of mean arterial pressure and renal sympathetic nerve activity (−19.0±1.5 mm Hg and −43.3±5.4%) were observed at 50 and 40 minutes, respectively, after intracerebroventricular injection of 1 nmol of ghrelin. Furthermore, a subdepressor dose of intracerebroventricular infusion of ghrelin (0.3 nmol/150 μL per hour) significantly augmented the baroreflex sensitivities assessed by renal sympathetic nerve activity and HR compared with those of vehicle infusion (G
max
; −17.8±3.1 versus −9.4±1.6%/mm Hg,
P
<0.05; −12.5±1.8 versus −6.6±1.2 bpm/mm Hg,
P
<0.05; respectively). These results suggest that intravenous injection of ghrelin acts, at least in part, on the central nervous system to decrease arterial pressure and renal sympathetic nerve activity, and that central ghrelin participates in the regulations of the sympathetic nerve activity to the kidney and the baroreceptor reflex in conscious rabbits.
Leptin Induces Endothelial Cell Migration Through Akt, Which Is Inhibited by PPARγ-Ligands
Authors: Goetze Stephan , Bungenstock Anne , Czupalla Cornelia , Eilers Friedrich , Stawowy Philipp , Kintscher Ulrich , Spencer-Hänsch Chantel , Graf Kristof , Nürnberg Bernd , Law Ronald E. , Fleck Eckart , Gräfe Michael
Published: October 2002

Migration of endothelial cells (EC) is a key event in angiogenesis that contributes to neovascularization in diabetic vasculopathy. Leptin induces angiogenesis and is elevated in obesity and hyperinsulinemia. The antidiabetic thiazolidinediones (TZD) inhibit leptin gene expression and vascular smooth muscle cell migration through activation of the peroxisome proliferator–activated receptor-γ (PPARγ). This study investigates the role of leptin in EC migration, the chemotactic signaling pathways involved, and the effects of the TZD-PPARγ ligands troglitazone (TRO) and ciglitazone (CIG) on EC migration. We demonstrate that leptin induces EC migration. Because activation of two signaling pathways, the phosphatidylinositol-3 kinase (PI3K)→Akt→eNOS and the ERK1/2 MAPK pathway, is known to be involved in cell migration, we used the pharmacological inhibitors wortmannin and PD98059 to determine if chemotactic signaling by leptin involves Akt or ERK1/2, respectively. Both wortmannin and PD98059 significantly inhibited leptin-induced migration. Treatment with the TZD-PPARγ-ligands TRO and CIG significantly inhibited the chemotactic response toward leptin. Both PPARγ-ligands inhibited leptin-stimulated Akt and eNOS phosphorylation, but neither attenuated ERK 1/2 activation in response to leptin. The inhibition of Akt-phosphorylation was accompanied by a PPARγ-ligand–mediated upregulation of PTEN, a phosphatase that functions as a negative regulator of PI3K→Akt signaling. These experiments provide the first evidence that activation of Akt and ERK 1/2 are crucial events in leptin-mediated signal transduction leading to EC migration. Moreover, inhibition of leptin-directed migration by the PPARγ-ligands TRO and CIG through inhibition of Akt underscores their potential in the prevention of diabetes-associated complications.
Is Cardiovascular Reactivity Associated With Atherosclerosis Among Hypertensives?
Authors: Gianaros Peter J. , Bleil Maria E. , Muldoon Matthew F. , Jennings J. Richard , Sutton-Tyrrell Kim , McCaffery Jeanne M. , Manuck Stephen B.
Published: October 2002

Exaggerated cardiovascular reactivity to behavioral challenges among otherwise healthy individuals has been associated with carotid atherosclerosis. We evaluated whether a similar relationship exists among hypertensives, who are at a heightened atherosclerotic risk. Untreated, hypertensive men (n=251; age range, 40 to 70 years; 197 white, 54 black) completed a standardized battery of behavioral challenges while their blood pressure responses to the battery were measured. Mean and maximum carotid intima-media thickness and the occurrence of carotid plaques were subsequently determined using B-mode ultrasonography. Although greater systolic and diastolic responses to the battery were associated with greater mean and maximum intima-media thickness in univariate analyses (
P
<0.01), only diastolic reactivity showed a unique association with mean and maximum carotid intima-media thickness after multivariate adjustment for age, race, socioeconomic status, smoking and alcohol use, body mass index, lipid profile, glucose and insulin concentrations, and resting blood pressure (
P
<0.05). Carotid plaque occurrence was associated with greater systolic reactivity (
P
=0.05) and was marginally associated with greater diastolic reactivity (
P
=0.07) in univariate analyses, but neither systolic nor diastolic reactivity was uniquely associated with the presence of carotid plaques after multivariate risk-factor adjustment. Among hypertensives, exaggerated behaviorally evoked cardiovascular reactivity appears to be uniquely associated with greater carotid intima-media thickness but not with carotid plaque occurrence.
Treatment and Control of Hypertension in the Community
Authors: Lloyd-Jones Donald M. , Evans Jane C. , Larson Martin G. , Levy Daniel
Published: October 2002

Cross-sectional national data indicate poor levels of treatment and control of hypertension. We identified factors that prospectively predict initiation of antihypertensive therapy and attainment of blood pressure control in the community. We included all Framingham Heart Study subjects examined between 1987 and 1999 who had untreated or uncontrolled hypertension (systolic ≥140 or diastolic ≥90 mm Hg) at a baseline examination and presented for follow-up examination 4 years later. Clinical covariates were examined for their association with initiation or control at follow-up. Among 1103 hypertensive participants who were untreated at baseline, 350 (31.7%) subjects were receiving therapy at follow-up, including 25.7% of subjects with stage 1 and 51.2% of those with stage ≥2 hypertension at baseline. Multivariate predictors of initiation of therapy included higher systolic and diastolic pressure, prevalent and interim cardiovascular disease, and left ventricular hypertrophy. Other cardiovascular risk factors did not predict initiation of treatment. Among 2475 hypertensive participants who were uncontrolled (treated or untreated) at baseline, 988 (39.9%) were controlled at follow-up. Prevalent cardiovascular disease and interim initiation of therapy predicted control; older age and higher baseline systolic levels predicted lack of control. These data provide estimates of longitudinal rates of treatment and control of hypertension in the community. It appears that global risk was not taken into consideration when making decisions for initiation of therapy. Greater emphasis is needed on achieving blood pressure control in all patients but particularly among older subjects and those with systolic hypertension.
Antiinflammatory and Antiarteriosclerotic Effects of Pioglitazone
Authors: Ishibashi Minako , Egashira Kensuke , Hiasa Ken-ichi , Inoue Shujiro , Ni Weihua , Zhao Qingwei , Usui Makoto , Kitamoto Shiro , Ichiki Toshihiro , Takeshita Akira
Published: October 2002

Peroxisome proliferator-activated receptor-γ (PPARγ) ligands are widely used in patients with insulin resistance and diabetes. Because coronary artery disease is a major complication for such patients, it is important to determine the effects of PPARγ activation on arteriosclerosis. Long-term inhibition of endothelial NO synthesis by administration of
N
ω
-nitro-
l
-arginine methyl ester (L-NAME) to rats induces coronary vascular inflammation (monocyte infiltration, monocyte chemoattractant protein-1 [MCP-1] expression) and subsequent arteriosclerosis. We examined the effects of pioglitazone (a PPARγ ligand) in this rat model to determine whether PPARγ activation with pioglitazone inhibits arteriosclerosis by its indirect effects on metabolic conditions or by direct effects on the cells participating to the pathogenesis of arteriosclerosis. We found that pioglitazone did not affect metabolic states, systolic blood pressure, or serum NO levels, but did prevent the L-NAME–induced coronary inflammation and arteriosclerosis. Pioglitazone did not reduce local expression of MCP-1 but markedly attenuated increased expression of the MCP-1 receptor C-C chemokine receptor 2 (CCR2) in lesional and circulating monocytes. PPARγ activation with pioglitazone prevented coronary arteriosclerosis, possibly by its antiinflammatory effects (downregulation of CCR2 in circulating monocytes). Inhibition of the CCR2-mediated inflammation may represent novel antiinflammatory actions of pioglitazone beyond improvement of metabolic state.
Aldosterone Antagonist Improves Diastolic Function in Essential Hypertension
Authors: Grandi Anna M. , Imperiale Daniela , Santillo Rosa , Barlocco Elena , Bertolini Andrea , Guasti Luigina , Venco Achille
Published: October 2002

Experimental studies demonstrated that mineralocorticoid antagonists prevent or reverse myocardial fibrosis. Therefore, we tested the hypothesis that the aldosterone antagonist canrenone can improve left ventricular diastolic function in essential hypertension. Using digitized M-mode echocardiography and 24-hour blood pressure monitoring (ABPM), we realized a prospective, randomized, controlled study on 34 never-treated essential hypertensives with left ventricular diastolic dysfunction. Echocardiogram and ABPM were repeated after 6 months of effective antihypertensive treatment with ACE inhibitors and calcium antagonists (second evaluation) and then after a 6-month period with 17 patients randomly assigned to add canrenone 50 mg/d to the previous treatment (third evaluation). At the basal evaluation 32 patients had left ventricular concentric hypertrophy, and 2 patients had left ventricular concentric remodeling. All the patients had normal left ventricular systolic function. At the second evaluation blood pressure was reduced (
P
<0.0001), left ventricular mass index decreased (
P
<0.0001), and diastolic function improved (
P
<0.0001). After randomization, the canrenone and control groups had similar 24-hour blood pressure and left ventricular morpho-functional characteristics. At the third evaluation, despite unchanged blood pressure and similar decrease of left ventricular mass index, the canrenone group, compared with control group, showed a significantly greater increase in left ventricular diastolic indices. In essential hypertension, a low dose of aldosterone antagonist added to antihypertensive treatment significantly improved left ventricular diastolic function. This improvement, not accounted for by changes in blood pressure and left ventricular mass, can be therefore ascribed to a direct action of the drug on the myocardium.
Identification of Hypertension-Related QTLs in African American Sib Pairs
Authors: Kotchen Theodore A. , Broeckel Ulrich , Grim Clarence E. , Hamet Pavel , Jacob Howard , Kaldunski Mary L. , Kotchen Jane Morley , Schork Nicholas J. , Tonellato Peter J. , Cowley Allen W.
Published: October 2002

To link hypertension-related phenotypes with chromosomal loci, genome scans were performed in 150 African American sib pairs concordant for essential hypertension. Phenotypes included blood pressure, anthropomorphic measurements, and estimates of body fluid compartments as determined by impedance plethysmography. These phenotypes were also measured in 335 normotensive African Americans. Phenotypes with LOD scores >3.3 were further evaluated for significance by use of permutation procedures. Significant linkage was detected for body mass index (BMI) on chromosomes 1 and 8 and for the ratio of extracellular water to total body water (ECF/TBW) on chromosomes 3, 5, 6, and 7. Both BMI and ECF/TBW were greater in hypertensive sibs than in normotensive subjects (
P
<0.001). In a subset of hypertensive sibs and normotensive subjects, average 24-hour blood pressures were correlated with ECF/TBW (
P
<0.01). A region linked to BMI in the hypertensive sibs corresponds to a region of conserved synteny containing blood pressure–related QTLs in an F2 cross of Brown Norway×Dahl salt-sensitive rats. Focusing on hypertension-related phenotypes is a promising approach for identifying the genetic determinants of hypertension.
Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells
Authors: Sharma Arya M. , Janke Jürgen , Gorzelniak Kerstin , Engeli Stefan , Luft Friedrich C.
Published: October 2002

Obesity is the prime risk factor for the development of type 2 diabetes. Recent clinical trials have shown that blockade of the renin-angiotensin system, either by inhibiting the angiotensin-converting enzyme or blocking the angiotensin type 1 receptor, may substantially lower the risk for type 2 diabetes. The mechanism underlying this effect is unknown. Based on our recent observation that angiotensin II markedly inhibits adipogenic differentiation of human adipocytes via the angiotensin type I receptor and that expression of angiotensin II–forming enzymes in adipose tissue is inversely correlated with insulin sensitivity, we propose the hypothesis that blockade of the renin-angiotensin system prevents diabetes by promoting the recruitment and differentiation of adipocytes. Increased formation of adipocytes would counteract the ectopic deposition of lipids in other tissues (muscle, liver, pancreas), thereby improving insulin sensitivity and preventing the development of type 2 diabetes.
Biphasic Regulation of Na
+
-HCO
3
−
Cotransporter by Angiotensin II Type 1A Receptor
Authors: Horita Shoko , Zheng Yanan , Hara Chiaki , Yamada Hideomi , Kunimi Motoei , Taniguchi Shigeo , Uwatoko Shu , Sugaya Takeshi , Goto Atsuo , Fujita Toshiro , Seki George
Published: October 2002

Although angiotensin (Ang) II is known to regulate renal proximal transport in a biphasic way, the receptor subtype(s) mediating these Ang II effects remained to be established. To clarify this issue, we compared the effects of Ang II in wild-type mice (WT) and Ang II type 1A receptor–deficient mice (AT
1A
KO). The Na
+
-HCO
3
−
cotransporter (NBC) activity, analyzed in isolated nonperfused tubules with a fluorescent probe, was stimulated by 10
−10
mol/L Ang II but was inhibited by 10
−6
mol/L Ang II in WT. Although valsartan (AT
1
antagonist) blocked both stimulation and inhibition by Ang II, PD 123,319 (AT
2
antagonist) did not modify these effects of Ang II. In AT
1A
KO, in contrast, this biphasic regulation was lost, and only stimulation of NBC activity by 10
−6
mol/L Ang II was observed. This stimulation was blocked by valsartan but not by PD 123,319. More than 10
−8
mol/L Ang II induced a transient increase in cell Ca
2+
concentrations in WT, which was again blocked by valsartan but not by PD 123,319. However, up to 10
−5
mol/L Ang II did not increase cell Ca
2+
concentrations in AT
1A
KO. Finally, the addition of arachidonic acid inhibited the NBC activity similarly in WT and AT
1A
KO, suggesting that the inhibitory pathway involving P-450 metabolites is preserved in AT
1A
KO. These results indicate that AT
1A
mediates the biphasic regulation of NBC. Although low-level expression of AT
1B
could be responsible for the stimulation by 10
−6
mol/L Ang II in AT
1A
KO, no evidence was obtained for AT
2
involvement.
Results of the
D
iet,
E
xercise, and
W
eight Loss
I
ntervention
T
rial (DEW-IT)
Authors: Miller Edgar R. , Erlinger Thomas P. , Young Deborah R. , Jehn Megan , Charleston Jeanne , Rhodes Donna , Wasan Sharmeel K. , Appel Lawrence J.
Published: October 2002

National guidelines for the prevention and treatment of hypertension recommend sodium reduction, weight loss, the Dietary Approach to Stop Hypertension (DASH) diet, and regular aerobic exercise. However, no trial has assessed the efficacy of simultaneously implementing all of these recommendations. The objective of this study was to determine the effects on blood pressure and other cardiovascular disease risk factors of a comprehensive lifestyle intervention. We conducted a randomized controlled trial of 44 hypertensive, overweight adults on a single blood pressure medication. Participants were randomized to a lifestyle or control group. For 9 weeks, the lifestyle group was fed a hypocaloric version of the DASH diet that provided 100 mmol/d of sodium. This group also participated in a supervised, moderate-intensity exercise program 3 times per week. The control group received no intervention. Outcomes were ambulatory blood pressure, serum lipids, weight, and fitness. At the end of the intervention, mean weight loss in the lifestyle group, net of control, was 4.9 kilograms. In the lifestyle group mean net reductions in 24-hour ambulatory systolic and diastolic blood pressures were 9.5 mm Hg (
P
<0.001) and 5.3 mm Hg (
P
<0.002), respectively. Corresponding changes in daytime systolic and diastolic blood pressures were 12.1 mm Hg (
P
<0.001) and 6.6 mm Hg (
P
<0.001). The lifestyle group experienced mean reductions in total cholesterol (−25 mg/dL,
P
<0.001), low-density lipoprotein cholesterol (−18 mg/dL,
P
=0.005), high-density lipoprotein cholesterol (−5 mg/dL,
P
<0.001), net of control. In conclusion, among hypertensive overweight adults already on antihypertensive medication, a comprehensive lifestyle intervention can substantially lower blood pressure and improve blood pressure control.
Estrogen Causes Dynamic Alterations in Endothelial Estrogen Receptor Expression
Authors: Ihionkhan Christopher E. , Chambliss Ken L. , Gibson Linda L. , Hahner Lisa D. , Mendelsohn Michael E. , Shaul Philip W.
Published: October 2002

Estrogen receptor (ER)α mediates many of the effects of estrogen on the vascular endothelium. The purpose of the present study was to determine whether estrogen modifies endothelial ERα expression. In experiments in cultured ovine endothelial cells, physiological concentrations of 17β-estradiol (E
2
, 10
−10
to 10
−8
mol/L) caused an increase in ERα protein abundance that was evident after 6 hours of hormone exposure. Shorter (2-hour) E
2
treatment caused ERα downregulation. In contrast to the upregulation in ERα after long-term E
2
, the expression of the other ER isoform, ERβ, was downregulated. Both nonselective ER antagonism with ICI 182,780 and the inhibition of gene transcription with actinomycin D blocked the increase in ERα with E
2
. In studies using the human ERα gene promoter P-1 coupled to luciferase, an increase in ERα gene transcription was evident in endothelial cells within 4 hours of E
2
exposure. The transcriptional activation was fully blocked by ICI 182,780, whereas the specific ERβ antagonist RR-tetrahydrochrysene yielded partial blockade. Overexpression of ERα or ERβ caused comparable 10- and 8-fold increases, respectively, in ERα promoter activation by E
2.
Thus, long-term exposure to E
2
upregulates ERα expression in endothelial cells through the actions of either ERα or ERβ on ERα gene transcription; in contrast, E
2
causes ERβ downregulation in the endothelium. We postulate that E
2
-induced changes in ERα and ERβ expression modify the effects of the hormone on vascular endothelium.
Role of Integrins in Endothelial Mechanosensing of Shear Stress
Authors: Shyy John Y.-J. , Chien Shu
Published: October 2002

The focal pattern of atherosclerotic lesions in arterial vessels suggests that local blood flow patterns are important factors in atherosclerosis. Although disturbed flows in the branches and curved regions are proatherogenic, laminar flows in the straight parts are atheroprotective. Results from in vitro studies on cultured vascular endothelial cells with the use of flow channels suggest that integrins and the associated RhoA small GTPase play important roles in the mechanotransduction mechanism by which shear stress is converted to cascades of molecular signaling to modulate gene expression. By interacting dynamically with extracellular matrix proteins, the mechanosensitive integrins activate RhoA and many signaling molecules in the focal adhesions and cytoplasm. Through such mechanotransduction mechanisms, laminar shear stress upregulates genes involved in antiapoptosis, cell cycle arrest, morphological remodeling, and NO production, thus contributing to the atheroprotective effects. This review summarizes some of the recent findings relevant to these mechanotransduction mechanisms. These studies show that integrins play an important role in mechanosensing in addition to their involvement in cell attachment and migration.
Development of the Coronary Vessel System
Authors: Reese David E. , Mikawa Takashi , Bader David M.
Published: October 2002

Formation of the coronary vessels is a fundamental event in heart development. Congenital abnormalities in the coronary system can have major deleterious effects on heart function. It is also possible that subtle variation in the patterning of coronary vessels has significant but uncharacterized effects on myocardial structure and function. In addition, generation of the coronary vascular system represents a complex system for analysis of regulation of cell fate determination, cell and epithelial migration, epithelial/mesenchymal transition, and patterning of a complex three-dimensional structure. In this review, we present the descriptive embryology of this process as well as the recent data that shed light on the unique developmental mechanisms underlying generation of coronary vessels. This review also attempts to identify areas where additional research is needed and highlights the questions that must be answered for a meaningful understanding of coronary vessel development.
Matrix Metalloproteinase-9 Is Necessary for the Regulation of Smooth Muscle Cell Replication and Migration After Arterial Injury
Authors: Cho Aesim , Reidy Michael A.
Published: October 2002

Matrix metalloproteinases (MMPs) and, in particular, MMP-9 are important for smooth muscle cell (SMC) migration into the intima. In this study, we sought to determine whether MMP-9 is critical for SMC migration and for the formation of a neointima by using mice in which the gene was deleted (MMP-9
−/−
mice). A denuding injury to the arteries of wild-type mice promoted the migration of medial SMCs into the neointima at 6 days, and a large neointimal lesion was observed after 28 days. In wild-type arteries, medial SMC replication was ≈8% at day 4, 6% at day 6, and 4% at day 8 and had further decreased to 1% at day 14. Intimal cell replication was 65% at 8 days and had decreased to ≈10% at 14 days after injury. In MMP-9
−/−
arteries, SMC replication was significantly lower at day 8. In addition, SMC migration and arterial lesion growth were significantly impaired in MMP-9
−/−
arteries. SMCs, isolated from MMP-9
−/−
mouse arteries, showed an impairment of migration and replication in vitro. Thus, our present data indicate that MMP-9 is critical for the development of arterial lesions by regulating both SMC migration and proliferation.
Ras/Erk Signaling Is Essential for Activation of Protein Synthesis by Gq Protein-Coupled Receptor Agonists in Adult Cardiomyocytes
Authors: Wang Lijun , Proud Christopher G.
Published: October 2002

The Gq protein-coupled receptor agonists phenylephrine (PE) and endothelin-1 (ET-1) induce cardiac hypertrophy and stimulate protein synthesis in cardiomyocytes. This study aims to investigate how they activate mRNA translation in adult cardiomyocytes. PE and ET-1 do not activate protein kinase B but stimulate Ras and Erk, and their ability to activate protein synthesis was blocked by inhibition of Ras or MEK and by rapamycin, which inhibits mTOR (mammalian target of rapamycin). These agonists activated ribosomal protein S6 kinase 1 (S6K1) and induced phosphorylation of eIF4E-binding protein-1 (4E-BP1) and its release from eIF4E. These effects were blocked by inhibitors of MEK. Furthermore, adenovirus-mediated expression of constitutively-active MEK1 caused activation of S6K1, phosphorylation of 4E-BP1, and activation of protein synthesis in a rapamycin-sensitive manner. Expression of N17Ras inhibited the regulation of S6K1 and protein synthesis by GqPCR agonists. These data point to a signaling pathway involving Ras and MEK that acts, with mTOR, to control regulatory translation factors and activate protein synthesis. This study provides new insights into the mechanisms underlying the stimulation of protein synthesis by hypertrophic agents in heart.
Somatosensory Gating and Recovery From Stroke Involving the Thalamus
Authors: Staines W. Richard , Black Sandra E. , Graham Simon J. , McIlroy William E.
Published: October 2002

Background and Purpose—

In the undamaged brain, sensory input to the cortex is intricately controlled via sensory gating mechanisms. Given the role of corticothalamic pathways in this control, it was hypothesized that in patients recovering from thalamic stroke there would be evidence of disrupted sensory gating and that efficient control of cortical sensory inputs would emerge during recovery.

Methods—

Four patients were tested serially after stroke from 1 to 24 weeks after injury. Perceptual thresholds, somatosensory evoked potential amplitudes, and functional MRI activations under specific somatosensory stimulation conditions were measured.

Results—

All patients demonstrated comparable results, revealing disrupted threshold detection to vibrotactile stimuli in the presence of a concurrent competing, contralateral input. In contrast, threshold detection was comparable between the affected and unaffected sides when there were no competing stimuli. This compromised capacity to inhibit competing sensory inputs was paralleled by a reduction in the measured activation of cortical representation in the stroke-affected hemisphere (functional MRI and somatosensory evoked potential) during bilateral stimulation. After recovery, perceptual detection improvements during bilateral stimulation were paralleled by enhancements of primary somatosensory cortical activation in the stroke-affected hemisphere.

Conclusions—

These results provide insight into potential mechanisms that contribute to sensory gating and suggest that the ability to control sensory input through effective gating mechanisms, in addition to primary somatosensory representation, may be important for poststroke sensory recovery.
Arterial Changes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Relation to Pathogenesis of Diffuse Myelin Loss of Cerebral White Matter
Authors: Okeda Riki , Arima Kunimasa , Kawai Mitsuru
Published: October 2002

Background and Purpose—

There is little information regarding the pathogenesis underlying diffuse myelin loss in the cerebral white matter and sparing of the U fibers in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in which the medial smooth muscle cells of systemic arteries are characteristically involved. We sought to examine the precise extent and severity of changes in the cerebral arteries in an autopsy case of CADASIL in relation to pathogenesis of the diffuse myelin loss.

Methods—

We reconstructed 1000 serial sections of the frontal cerebral medullary arteries of an autopsy subject, which was the first identified Japanese case of CADASIL, as confirmed by the presence of ultrastructural deposits of granular osmiophilic material in the media of some visceral arteries and by genetic analysis.

Results—

We reconstructed 11 medullary arteries of the frontal lobe showing diffuse myelin loss and atrophy of the white matter with sparing of the U fibers. All of these showed complete loss of medial smooth muscle cells over their entire length and severe adventitial fibrosis. Although intimal fibrosis or hyalinosis was present, luminal occlusion was scarce. These changes were also observed in the small and large arachnoidal arteries but were relatively mild in the latter and in the cortical and subcortical medullary arteries.

Conclusions—

These arterial changes resulted in transformation of the cerebral arteries, in particular almost all the medullary arteries, to a so-called earthen pipe state. This supports the reported findings of a reduction in vascular reactivity to fluctuations in CO
2
levels and systemic blood pressure in CADASIL.
Transient Focal Ischemia Increases Endothelial Nitric Oxide Synthase in Cerebral Blood Vessels
Authors: Veltkamp Roland , Rajapakse Nishadi , Robins Greg , Puskar Michelle , Shimizu Katsuyoshi , Busija David
Published: October 2002

Background and Purpose—

Production of NO by endothelial NO synthase (eNOS) plays a protective role in cerebral ischemia. We studied the effects of transient focal ischemia on eNOS expression.

Methods—

Wistar rats (n=72) underwent reversible filament occlusion of the right middle cerebral artery for 75 minutes. After 6, 24, 72, or 168 hours of reperfusion, brains were removed and coronal sections cut for eNOS immunohistochemistry, eNOS–alkaline phosphatase costaining, and hematoxylin-eosin staining. Samples for eNOS immunoblots were taken from corresponding striatum and overlying parietal cortex bilaterally.

Results—

eNOS protein occurred in virtually all blood vessels and was consistently increased in microvessels in the ischemic striatum after 24 to 168 hours of reperfusion but not at 6 hours. eNOS upregulation in the parietal cortex was only present in animals with evidence of cortical infarcts documented on adjacent HE-stained sections. Costaining of endogenous alkaline phosphatase and eNOS demonstrated eNOS expression in all segments of cerebral microvessels. Quantitative analysis of eNOS immunostaining and immunoblots showed no attenuated increase in animals that were treated with indomethacin (5 mg/kg IP), NS398 (20 mg/kg IP), or
l
-arginine-methyl ester (10 mg/kg IP). In contrast to eNOS, levels of brain NOS did not increase after ischemia.

Conclusion—

eNOS protein is upregulated in pre- and postcapillary microvessels and upregulation appears slower after transient compared with permanent ischemia. Cyclooxygenase and NOS products do not play a major role in postischemic eNOS induction.