bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of atrial natriuretic peptide on the extrasplenic microvasculature and lymphatics in the rat in vivo
Authors: Brookes Zoë L. S. , Kaufman Susan
Published: February 2005

We developed a novel model using fluorescent intravital microscopy to study the effect of atrial natriuretic peptide (ANP) on the extrasplenic microcirculation. Continuous infusion of ANP into the splenic artery (10 ng min−1 for 60 min) of male Long–Evans rats (220–250 g, n= 24) induced constriction of the splenic arterioles after 15 min (−7.2 ± 6.6% from baseline diameter of 96 ± 18.3 μm, mean ±s.e.m.) and venules (−14.4 ± 4.0% from 249 ± 25.8 μm; P < 0.05). At the same time flow did not change in the arterioles (from 1.58 ± 0.34 to 1.27 ± 0.27 ml min−1), although it decreased in venules (from 1.67 ± 0.23 to 1.15 ± 0.20 ml min−1) and increased in the lymphatics (from 0.007 ± 0.001 to 0.034 ± 0.008 ml min−1; P < 0.05). There was no significant change in mean arterial pressure (from 118 ± 5 to 112 ± 5 mmHg). After continuous ANP infusion for 60 min, the arterioles were dilated (108 ± 16 μm, P < 0.05) but the venules remained constricted (223 ± 24 μm). Blood flow decreased in both arterioles (0.76 ± 0.12 ml min−1) and venules (1.03 ± 0.18 ml min−1; P < 0.05), but was now unchanged from baseline in the lymphatics (0.01 ± 0.001 ml min−1). This was accompanied by a significant decrease in MAP (104 ± 5 mmHg; P < 0.05). At 60 min, there was macromolecular leak from the lymphatics, as indicated by increased interstitial fluorescein isothiocyanate–bovine serum albumin fluorescence (grey level: 0 = black; 255 = white; from 55.8 ± 7.6 to 71.8 ± 5.9, P < 0.05). This study confirms our previous proposition that, in the extrasplenic microcirculation, ANP causes greater increases in post‐ than precapillary resistance, thus increasing intrasplenic capillary hydrostatic pressure (Pc) and fluid efflux into the lymphatic system. Longer‐term infusion of ANP also increases Pc, but this is accompanied by increased ‘permeability’ of the extrasplenic lymphatics, such that fluid is lost to perivascular third spaces.
Reactive oxygen species reduce myofibrillar Ca2+ sensitivity in fatiguing mouse skeletal muscle at 37°C
Authors: Moopanar Terence R. , Allen David G.
Published: February 2005

The mechanisms of muscle fatigue were studied in small muscle bundles and single fibres isolated from the flexor digitorum brevis of the mouse. Fatigue caused by repeated isometric tetani was accelerated at body temperature (37°C) when compared to room temperature (22°C). The membrane‐permeant reactive oxygen species (ROS) scavenger, Tiron (5 mm), had no effect on the rate of fatigue at 22°C but slowed the rate of fatigue at 37°C to that observed at 22°C. Single fibres were microinjected with indo‐1 to measure intracellular calcium. In the accelerated fatigue at 37°C the tetanic [Ca2+]i did not change significantly and the decline of maximum Ca2+‐activated force was similar to that observed at 22°C. The cause of the greater rate of fatigue at 37°C was a large fall in myofibrillar Ca2+ sensitivity. In the presence of Tiron, the large fall in Ca2+ sensitivity was abolished and the usual decline in tetanic [Ca2+]i was observed. This study confirms the importance of ROS in fatigue at 37°C and shows that the mechanism of action of ROS is a decline in myofibrillar Ca2+ sensitivity.
Sulfates in Martian Layered Terrains: The OMEGA/Mars Express View
Authors: Gendrin Aline , Mangold Nicolas , Bibring Jean-Pierre , Langevin Yves , Gondet Brigitte , Poulet François , Bonello Guillaume , Quantin Cathy , Mustard John , Arvidson Ray , LeMouélic Stéphane
Published: February 2005

The OMEGA/Mars Express hyperspectral imager identified hydrated sulfates on light-toned layered terrains on Mars. Outcrops in Valles Marineris, Margaritifer Sinus, and Terra Meridiani show evidence for kieserite, gypsum, and polyhydrated sulfates. This identification has its basis in vibrational absorptions between 1.3 and 2.5 micrometers. These minerals constitute direct records of the past aqueous activity on Mars.
Sulfates in the North Polar Region of Mars Detected by OMEGA/Mars Express
Authors: Langevin Yves , Poulet François , Bibring Jean-Pierre , Gondet Brigitte
Published: February 2005

The Observatoire pour la Minéralogie, l'Eau, les Glaces, et l'Activité (OMEGA) imaging spectrometer observed the northern circumpolar regions of Mars at a resolution of a few kilometers. An extended region at 240°E, 85°N, with an area of 60 kilometers by 200 kilometers, exhibits absorptions at wavelengths of 1.45, 1.75, 1.94, 2.22, 2.26, and 2.48 micrometers. These signatures can be unambiguously attributed to calcium-rich sulfates, most likely gypsum. This region corresponds to the dark longitudinal dunes of Olympia Planitia. These observations reveal that water alteration played a major role in the formation of the constituting minerals of northern circumpolar terrains.
Spectral Reflectance and Morphologic Correlations in Eastern Terra Meridiani, Mars
Authors: Arvidson R. E. , Poulet F. , Bibring J.-P. , Wolff M. , Gendrin A. , Morris R. V. , Freeman J. J. , Langevin Y. , Mangold N. , Bellucci G.
Published: February 2005

The Mars Express Observatoire pour la Minéralogie, l'Eau, les Glaces, et l'Activité (OMEGA) hyperspectral image data covering eastern Terra Meridiani indicate the ubiquitous presence of molecular water in etched terrain materials that disconformably overlie heavily cratered terrains and underlie the hematite-bearing plains explored by the Opportunity rover. Identification of crystalline water in kieserite (MgSO
4
·H
2
O) is linked to materials exposed in a valley and plateau to the north of hematite-bearing plains. The mineralogical similarities between the etched terrain deposits examined with OMEGA data and the layered rocks examined by Opportunity imply that the ancient aqueous environments inferred from analyses of the rover data extend over regional scales.
Wave-energy patterns in carotid, brachial, and radial arteries: a noninvasive approach using wave-intensity analysis
Authors: Zambanini A. , Cunningham S. L. , Parker K. H. , Khir A. W. , McG. Thom S. A. , Hughes A. D.
Published: February 2005

The study of wave propagation at different points in the arterial circulation may provide useful information regarding ventriculoarterial interactions. We describe a number of hemodynamic parameters in the carotid, brachial, and radial arteries of normal subjects by using noninvasive techniques and wave-intensity analysis (WIA). Twenty-one normal adult subjects (14 men and 7 women, mean age 44 ± 6 yr) underwent applanation tonometry and pulsed-wave Doppler studies of the right common carotid, brachial, and radial arteries. After ensemble averaging of the pressure and flow-velocity data, local hydraulic work was determined and a pressure-flow velocity loop was used to determine local wave speed. WIA was then applied to determine the magnitude, timings, and energies of individual waves. At all sites, forward-traveling (S) and backward-traveling (R) compression waves were observed in early systole. In mid- and late systole, forward-traveling expansion waves (X and D) were also seen. Wave speed was significantly higher in the brachial (6.97 ± 0.58 m/s) and radial (6.78 ± 0.62 m/s) arteries compared with the carotid artery (5.40 ± 0.34 m/s; P < 0.05). S-wave energy was greatest in the brachial artery (993.5 ± 87.8 mJ/m2), but R-wave energy was greatest in the radial artery (176.9 ± 19.9 mJ/m2). X-wave energy was significantly higher in the brachial and radial arteries (176.4 ± 32.7 and 163.2 ± 30.5 mJ/m2, respectively) compared with the carotid artery (41.0 ± 9.4 mJ/m2; P < 0.001). WIA illustrates important differences in wave patterns between peripheral arteries and may provide a method for understanding ventriculo-arterial interactions in the time domain.
Resonance in a mathematical model of baroreflex control: arterial blood pressure waves accompanying postural stress
Authors: Hammer Peter E. , Saul J. Philip
Published: February 2005

A mathematical model of the arterial baroreflex was developed and used to assess the stability of the reflex and its potential role in producing the low-frequency arterial blood pressure oscillations called Mayer waves that are commonly seen in humans and animals in response to decreased central blood volume. The model consists of an arrangement of discrete-time filters derived from published physiological studies, which is reduced to a numerical expression for the baroreflex open-loop frequency response. Model stability was assessed for two states: normal and decreased central blood volume. The state of decreased central blood volume was simulated by decreasing baroreflex parasympathetic heart rate gain and by increasing baroreflex sympathetic vaso/venomotor gains as occurs with the unloading of cardiopulmonary baroreceptors. For the normal state, the feedback system was stable by the Nyquist criterion (gain margin = 0.6), but in the hypovolemic state, the gain margin was small (0.07), and the closed-loop frequency response exhibited a sharp peak (gain of 11) at 0.07 Hz, the same frequency as that observed for arterial pressure fluctuations in a group of healthy standing subjects. These findings support the theory that stresses affecting central blood volume, including upright posture, can reduce the stability of the normally stable arterial baroreflex feedback, leading to resonance and low-frequency blood pressure waves.
Interactions between 11β-hydroxysteroid dehydrogenase and COX-2 in kidney
Authors: Yao Bing , Harris Raymond C. , Zhang Ming-Zhi
Published: February 2005

The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal recessive form of salt-sensitive hypertension caused by deficiency of the kidney type 2 11β-hydroxysteroid dehydrogenase (11βHSD2). In this disorder, cortisol is not inactivated by 11βHSD2, occupies mineralocorticoid receptors (MRs), and causes excessive sodium retention and hypertension. In renal medulla, prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water excretion, and renal medullary COX-2 expression increases after mineralocorticoid administration. We investigated whether medullary COX-2 also increases in rats with 11βHSD2 inhibition and examined its possible role in the development of hypertension. 11βHSD2 inhibition increased medullary and decreased cortical COX-2 expression in adult rats and induced high blood pressure in high-salt-treated rats. COX-2 inhibition had no effect on blood pressure in control animals but further increased blood pressure in high-salt-treated rats with 11βHSD2 inhibition. COX-1 inhibition had no effect on blood pressure in either control or experimental animals. 11βHSD2 inhibition also led to medullary COX-2 increase and cortical COX-2 decrease in weaning rats, primarily through activation of MRs. In the suckling rats, medullary COX-2 expression was very low, consistent with a urinary concentrating defect. 11βHSD2 inhibition had no effect on either cortical or medullary COX-2 expression in the suckling rats, consistent with low levels of circulating corticosterone in these animals. These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11βHSD2 deficiency and that 11βHSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development.
Cytosolic phospholipase A2α regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation
Authors: Sapirstein Adam , Saito Hideyuki , Texel Sarah J. , Samad Tarek A. , O’Leary Eileen , Bonventre Joseph V.
Published: February 2005

The products of arachidonic acid metabolism are key mediators of inflammatory responses in the central nervous system, and yet we do not know the mechanisms of their regulation. The phospholipase A2 enzymes are sources of cellular arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE2 in the brain. These studies seek to determine the function of cytosolic phospholipase A2α (cPLA2α) in inflammatory PGE2 production in the brain. We wondered whether cPLA2α functions in inflammation to produce arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these questions in the brains of wild-type mice and mice deficient in cPLA2α (cPLA2α−/−) after systemic administration of LPS. cPLA2α−/− mice had significantly less brain COX-2 mRNA and protein expression in response to LPS than wild-type mice. The reduction in COX-2 was most apparent in the cells of the cerebral blood vessels and the leptomeninges. The brain PGE2 concentration of untreated cPLA2α−/− mice was equal to their wild-type littermates. After LPS treatment, however, the brain concentration of PGE2 was significantly less in cPLA2α−/− than in cPLA2α+/+ mice (24.4 ± 3.8 vs. 49.3 ± 11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude that cPLA2α regulates COX-2 levels and modulates inflammatory PGE2 levels. These results indicate that cPLA2α inhibition is a novel anti-inflammatory strategy that modulates, but does not completely prevent, eicosanoid responses.
Dehydration anorexia is attenuated in oxytocin-deficient mice
Authors: Rinaman Linda , Vollmer Regis R. , Karam Joseph , Phillips Donnesha , Li Xia , Amico Janet A.
Published: February 2005

Evidence in rats suggests that central oxytocin (OT) signaling pathways contribute to suppression of food intake during dehydration (i.e., dehydration anorexia). The present study examined water deprivation-induced dehydration anorexia in wild-type and OT −/− mice. Mice were deprived of food alone (fasted, euhydrated) or were deprived of both food and water (fasted, dehydrated) for 18 h overnight. Fasted wild-type mice consumed significantly less chow during a 60-min refeeding period when dehydrated compared with their intake when euhydrated. Conversely, fasting-induced food intake was slightly but not significantly suppressed by dehydration in OT −/− mice, evidence for attenuated dehydration anorexia. In a separate experiment, mice were deprived of water (but not food) overnight for 18 h; then they were anesthetized and perfused with fixative for immunocytochemical analysis of central Fos expression. Fos was elevated similarly in osmo- and volume-sensitive regions of the basal forebrain and hypothalamus in wild-type and OT −/− mice after water deprivation. OT-positive neurons expressed Fos in dehydrated wild-type mice, and vasopressin-positive neurons were activated to a similar extent in wild-type and OT −/− mice. Conversely, significantly fewer neurons within the hindbrain dorsal vagal complex were activated in OT −/− mice after water deprivation compared with activation in wild-type mice. These findings support the view that OT-containing projections from the hypothalamus to the hindbrain are necessary for the full expression of compensatory behavioral and physiological responses to dehydration.
Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats
Authors: Chelikani Prasanth K. , Haver Alvin C. , Reidelberger Roger D.
Published: February 2005

Glucagon-like peptide-1(7–36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5–170 pmol·kg−1·min−1) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol·kg−1·min−1 and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7–50 pmol·kg−1·min−1) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol·kg−1·min−1 and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5–50 pmol·kg−1·min−1) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.
Progesterone increases plasma volume independent of estradiol
Authors: Stachenfeld Nina S. , Taylor Hugh S.
Published: February 2005

Adequate plasma volume (PV) and extracellular fluid (ECF) volume are essential for blood pressure and fluid regulation. We tested the hypotheses that combined progesterone (P4)-estrogen (E2) administration would increase ECF volume with proportional increases in PV, but that P4would have little independent effect on either PV or ECF volume. We further hypothesized that this P4-E2-induced fluid expansion would be a function of renin-angiotensin-aldosterone system stimulation. We suppressed P4and E2with a gonadotropin-releasing hormone (GnRH) antagonist in eight women (25 ± 2 yr) for 16 days; P4(200 mg/day) was added for days 5–16 (P4) and 17β-estradiol (2 × 0.1 mg/day patches) for days 13–16 (P4-E2). On days 2 (GnRH antagonist), 9 (P4), and 16 (P4-E2), we estimated ECF and PV. To determine the rate of protein and thus water movement across the ECF, we also measured transcapillary escape rate of albumin. In P4, [Formula: see text] increased from 2.5 ± 1.3 to 12.0 ± 2.8 ng/ml ( P < 0.05) with no change in [Formula: see text] (21.5 ± 9.4 to 8.6 ± 2.0 pg/ml). In P4-E2, plasma concentration of P4remained elevated (11.3 ± 2.7 ng/ml) and plasma concentration of E2increased to 254.1 ± 52.7 pg/ml ( P < 0.05). PV increased during P4(46.6 ± 2.5 ml/kg) and P4-E2(48.4 ± 3.9 ml/kg) compared with GnRH antagonist (43.3 ± 3.2 ml/kg; P < 0.05), as did ECF (206 ± 19, 244 ± 25, and 239 ± 27 ml/kg for GnRH antagonist, P4, and P4-E2, respectively; P < 0.05). Transcapillary escape rate of albumin was lowest during P4-E2(5.8 ± 1.3, 3.5 ± 1.7, and 2.2 ± 0.4%/h for GnRH antagonist, P4, and P4-E2, respectively; P < 0.05). Serum aldosterone increased during P4and P4-E2compared with GnRH antagonist (79 ± 17, 127 ± 13, and 171 ± 25 pg/ml for GnRH antagonist, P4, and P4-E2, respectively; P < 0.05), but plasma renin activity and plasma concentration of ANG II were only increased by P4-E2. This study is the first to isolate P4effects on ECF; however, the mechanisms for the ECF and PV expansion have not been clearly defined.
Novel method for in vivo hydroxyl radical measurement by microdialysis in fetal sheep brain in utero
Authors: Yan Edwin B. , Unthank Jessica K. , Castillo-Melendez Margie , Miller Suzanne L. , Langford Steven J. , Walker David W.
Published: February 2005

Hydroxyl radical (·OH) is a reactive oxygen species produced during severe hypoxia, asphyxia, or ischemia that can cause cell death resulting in brain damage. Generation of ·OH may occur in the fetal brain during asphyxia in utero. The very short half-life of ·OH requires use of trapping agents such as salicylic acid or phenylalanine for detection, but their hydroxylated derivatives are either unstable, produced endogenously, or difficult to measure in the small volume of microdialysis samples. In the present study, we used terephthalic acid (TA), hydroxylation of which yields a stable and highly fluorometric isomer (excitation, 326 nm; emission, 432 nm). In vitro studies using ·OH generated by the Fenton reaction showed that hydroxylated TA formed quickly (<10 s), was resistant to bleaching (<5% change in fluorescence), and permitted detection of <0.5 pmol ·OH. In vivo studies were performed in fetal sheep using microdialysis probes implanted into the parasagittal cortex. The probe was perfused at 2 μl/min with artificial cerebrospinal fluid containing 5 mM TA, and samples were collected every 30 min. Fluorescence measured in 10 μl of dialysate was significantly greater than in the efflux from probes perfused without TA. High-performance liquid chromotography analysis showed that the fluorescence in dialysis samples was entirely due to hydroxylation of TA. Thus this study shows that it is possible to use TA as a trapping agent for detecting low concentrations of ·OH both in vitro and in vivo and that low concentrations of ·OH are present in fetal brain tissue and fluctuate with time.
ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women
Authors: Clarkson Priscilla M. , Devaney Joseph M. , Gordish-Dressman Heather , Thompson Paul D. , Hubal Monica J. , Urso Maria , Price Thomas B. , Angelopoulos Theodore J. , Gordon Paul M. , Moyna Niall M. , Pescatello Linda S. , Visich Paul S. , Zoeller Robert F. , Seip Richard L. , Hoffman Eric P.
Published: February 2005

The α-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627–631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men ( N = 247) and women ( N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes ( P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age ( P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.
Skeletal muscle fatigue, strength, and quality in the elderly: the Health ABC Study
Authors: Katsiaras Andreas , Newman Anne B. , Kriska Andrea , Brach Jennifer , Krishnaswami Shanthi , Feingold Eleanor , Kritchevsky Stephen B. , Li Rongling , Harris Tamara B. , Schwartz Ann , Goodpaster Bret H.
Published: February 2005

We examined the muscle fatigue characteristics in older men and women and determined whether these were related to the size, strength, or quality of muscle. A total of 1,512 men and women aged 70–79 yr from the Health, Aging, and Body Composition Study participated in this study. Muscle cross-sectional area and attenuation were determined with computed tomography. Skeletal muscle fatigue and strength (peak torque) of the knee extensors and flexors were measured using isokinetic dynamometry. Men were more fatigue resistant than women for both knee extension (fatigue index: 70.4 ± 15.3 vs. 66.9 ± 14.3%; P < 0.05) and knee flexion (67.9 ± 16.4 vs. 64.9 ± 17.6%; P < 0.05). Peak torque and muscle quality (specific torque) were higher in men than women for knee extension (99.6 ± 28.2 vs. 63.0 ± 16.8 N·m and 1.62 ± 0.43 vs. 1.51 ± 0.39 N·m/cm2; both P < 0.05) and for knee flexion (74.0 ± 26.4 vs. 49.6 ± 15.9 N·m and 2.47 ± 1.29 vs. 2.22 ± 0.78 N·m/cm2; both P < 0.05). Total work and power output was greater in men compared with women for both the quadriceps (1,353 ± 451 vs. 832 ± 264 J and 87.7 ± 33.5 vs. 53.3 ± 19.2 W; both P < 0.05) and the hamstrings (741 ± 244 vs. 510 ± 141 J and 35.4 ± 16.0 vs. 23.7 ± 10.2 W; both P < 0.05). In both genders, the quadriceps was able to perform more work with greater power compared with the hamstrings. Those who were stronger actually had greater fatigue after adjusting for age, race, physical activity, and total body fat. In conclusion, older men were more fatigue resistant than women, although in both men and women greater fatigue was not related to muscle weakness.
Expression and localization of caveolins during postnatal development in rat heart: implication of thyroid hormone
Authors: Ratajczak Philippe , Oliviéro Patricia , Marotte Françoise , Kolar Frantisek , Ostadal Bohuslav , Samuel Jane-Lise
Published: February 2005

Caveolins modulate signaling pathways involved in cardiac development. Caveolin-1 exists in two isoforms: the β-isoform derivates from an alternative translational start site that creates a protein truncated by 31 amino acids, mainly expressed in endothelial cells, whereas caveolin-3 is present in muscle cells. Our aim was to define caveolin distribution and expression during cardiac postnatal development using immunofluorescence and Western blotting. Caveolin-3 sarcolemmal labeling appeared as dotted lines from days 1 to 5 and as continuous lines after 14 days of age. Caveolin-3 expression, low at birth, increased (4-fold) to reach a maximum ( P < 0.05) by day 5 and then decreased to stabilize in adults. Total caveolin-1 and its α-isoform were codistributed at birth in endothelial and smooth muscle cells; afterward, only the caveolin-1α labeling became limited to endothelium. Quantitative analysis indicated a similar temporal pattern of both total caveolin-1 and caveolin-1α expression, suggesting that caveolin-1α and -1β are coregulated; the caveolin-1α levels increased fourfold by day 5 to reach a maximum by day 14 ( P < 0.05). Tyrosine-14-caveolin-1 phosphorylation, low at birth, increased suddenly around day 14 (8-fold vs. day 1) and returning afterward to basal level. Because the T3/T4 level is maximal by day 14, caveolin-1 expression/phosphorylation profiles were analyzed in hypothyroid heart. The levels of caveolin-1α and consequently tyrosine-14-caveolin-1 phosphorylation, but not that of caveolin-3, decreased (50%) in hypothyroid 14-day-old rats. Our data demonstrate that, during postnatal cardiac growth, 1) caveolins are distinctly regulated, and 2) thyroid hormones are involved in caveolin-1α expression.
Interleukin-6 and Mevastatin Regulate Plasminogen Activator Inhibitor-1 Through CCAAT/Enhancer-Binding Protein-δ
Authors: Dong Jie , Fujii Satoshi , Li Hongmei , Nakabayashi Hidekazu , Sakai Masaharu , Nishi Shinzo , Goto Daisuke , Furumoto Tomoo , Imagawa Shogo , Zaman Tarikuz A.K.M. , Kitabatake Akira
Published: February 2005

Objective—

We sought to determine the etiologic mechanism of proinflammatory cytokine, interleukin-6 (IL-6), and statin as regulators of synthesis of plasminogen activator inhibitor-1 (PAI-1), the physiological fibrinolysis inhibitor and an acute-phase reactant.

Methods and Results—

Transient transfection and luciferase assay in HepG2 human hepatoma-derived cells demonstrated that IL-6 increased PAI-1 promoter activity and mevastatin decreased IL-6–inducible response. Systematic deletion assay of the promoter demonstrated that the region (−239 to −210 bp) containing a putative CCAAT/enhancer-binding protein (C/EBP) binding site was necessary. Point mutation in this site abolished the IL-6–inducible response. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that C/EBPα, C/EBPβ, and C/EBPδ were involved in protein–DNA complex formation in intact cells. Deoxyribonuclease (DNase) I footprinting analysis revealed that 5′ flanking region (−232 to −210 bp) is acute-phase response protein-binding site. C/EBPδ binding activity was increased by IL-6 and attenuated by mevastatin. Mevastatin attenuated IL-6–mediated increase of C/EBPδ protein in the nuclear extracts. IL-6 also increased PAI-1 and C/EBPδ mRNA in mouse primary hepatocytes.

Conclusions—

IL-6 increases hepatic PAI-1 expression mediated by the −232- to −210-bp region of the promoter containing a C/EBPδ binding site. Vascular protection by statins may be partly mediated through regulation of CEBPδ and consequent modulation of PAI-1 expression.
Shear Stress Inhibits Smooth Muscle Cell–Induced Inflammatory Gene Expression in Endothelial Cells
Authors: Chiu Jeng-Jiann , Chen Li-Jing , Chang Shun-Fu , Lee Pei-Ling , Lee Chih-I , Tsai Min-Chien , Lee Ding-Yu , Hsieh Hsing-Pang , Usami Shunichi , Chien Shu
Published: February 2005

Objectives—

Vascular endothelial cells (ECs) are influenced by shear stress and neighboring smooth muscle cells (SMCs). We investigated the inflammation-relevant gene expression in EC/SMC cocultures under static condition and in response to shear stress.

Materials and Methods—

Under static condition, DNA microarrays and reverse-transcription polymerase chain reaction identified 23 inflammation-relevant genes in ECs whose expression was significantly affected by coculture with SMCs, with 18 upregulated and 5 downregulated. Application of shear stress (12 dynes/cm
2
) to the EC side of the coculture for 6 hours inhibited most of the proinflammatory gene expressions in ECs induced by coculture with SMCs. Inhibition of nuclear factor-κB (NF-κB) activation by the p65-antisense, lactacystin, and N-acetyl-cysteine blocked the coculture-induced EC expression of proinflammatory genes, indicating that the NF-κB binding sites in the promoters of these genes play a significant role in their expression as a result of coculture with SMCs. Chromatin immunoprecipitation assays demonstrated the in vivo regulation of NF-κB recruitment to selected target promoters. Shear stress inhibited the SMC coculture-induced NF-κB activation in ECs and monocytic THP-1 cell adhesion to ECs.

Conclusions—

Our findings suggest that shear stress plays an inhibitory role in the proinflammatory gene expression in ECs located in close proximity to SMCs.
Mixed Messages
Authors: Margulies Kenneth B. , Matiwala Sunil , Cornejo Carla , Olsen Henrik , Craven William A. , Bednarik Daniel
Published: February 2005

In previous studies, mechanical support of medically refractory hearts with a left ventricular assist device (LVAD) has induced regression of many morphological and functional abnormalities characteristic of failing human hearts. To identify transcriptional adaptations in failing and LVAD-supported hearts, we performed a comprehensive transcription analysis using the Affymetrix microarray platform and 199 human myocardial samples from nonfailing, failing, and LVAD-supported human hearts. We also used a novel analytical strategy that defines patterns of interest based on multiple intergroup comparisons. Although over 3088 transcripts exhibited significantly altered abundance in heart failure, most of these did not exhibit a consistent response to LVAD support based on our analysis. Of those 238 with a consistent response to LVAD support, more than 75% exhibited persistence or exacerbation of HF-associated transcriptional abnormalities whereas only 11%, 5%, and 2% exhibited partial recovery, normalization, and overcorrection responses, respectively. Even among genes implicated by previous reports of LVAD-associated myocardial improvements, partial or complete normalization of transcription did not predominate. The magnitude of differences in transcript abundance between nonfailing and failing hearts, and between failing an LVAD-supported hearts, tended to be low with changes greater than or equal to 2-fold infrequently observed. Our results indicate that morphological or functional myocardial improvements may occur without widespread normalization of pathological transcriptional patterns. These observations also suggest that many failure-associated transcriptional changes have only a limited role in regulating cardiac structure and function and may represent epiphenomena and/or nonspecific myocardial plasticity responses. Differences in mRNA localization, translation efficiency, and posttranslational protein modifications or interactions may be more pivotal in regulating myocardial structure and function.
Divergent Siblings
Authors: Ebelt Henning , Hufnagel Nadine , Neuhaus Petra , Neuhaus Herbert , Gajawada Praveen , Simm Andreas , Müller-Werdan Ursula , Werdan Karl , Braun Thomas
Published: February 2005

Proliferation of mammalian cardiomyocytes ceases around birth when a transition from hyperplastic to hypertrophic myocardial growth occurs. Previous studies demonstrated that directed expression of the transcription factor E2F1 induces S-phase entry in cardiomyocytes along with stimulation of programmed cell death. Here, we show that directed expression of E2F2 and E2F4 by adenovirus mediated gene transfer in neonatal cardiomyocytes induced S-phase entry but did not result in an onset of apoptosis whereas directed expression of E2F1 and E2F3 strongly evoked programmed cell death concomitant with cell cycle progression. Although both E2F2 and E2F4 induced S-phase entry only directed expression of E2F2 resulted in mitotic cell division of cardiomyocytes. Expression of E2F5 or a control LacZ-Adenovirus had no effects on cell cycle progression. Quantitative real time PCR revealed that E2F1, E2F2, E2F3, and E2F4 alleviate G0 arrest by induction of cyclinA and E cyclins. Furthermore, directed expression of E2F1, E2F3, and E2F5 led to a transcriptional activation of several proapoptotic genes, which were mitigated by E2F2 and E2F4. Our finding that expression of E2F2 induces cell division of cardiomyocytes along with a suppression of proapoptotic genes might open a new access to improve the regenerative capacity of cardiomyocytes.
Kruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function
Authors: Lin Zhiyong , Kumar Ajay , SenBanerjee Sucharita , Staniszewski Kristine , Parmar Kush , Vaughan Douglas E. , Gimbrone Michael A. , Balasubramanian Viji , García-Cardeña Guillermo , Jain Mukesh K.
Published: February 2005

The vascular endothelium maintains blood fluidity by inhibiting blood coagulation, inhibiting platelet aggregation, and promoting fibrinolysis. Endothelial cells lose these nonthrombogenic properties on exposure to proinflammatory stimuli. We recently identified the Kruppel-like factor KLF2 as a novel regulator of endothelial proinflammatory activation. Here it is found that KLF2 differentially regulates key factors involved in maintaining an antithrombotic endothelial surface. Overexpression of KLF2 strongly induced thrombomodulin (TM) and endothelial nitric oxide synthase (eNOS) expression and reduced plasminogen activator inhibitor-1 (PAI-1) expression. Furthermore, overexpression of KLF2 inhibited the cytokine-mediated induction of tissue factor (TF). In contrast, siRNA mediated knockdown of KLF2 reduced antithrombotic gene expression while inducing the expression of pro-coagulant factors. The functional importance of KLF2 was verified by in vitro clotting assays. By comparison to control infected cells, KLF2 overexpression increased blood clotting time as well as flow rates under basal and inflammatory conditions. In contrast, siRNA-mediated knockdown of KLF2 reduced blood clotting time and flow rates. These observations identify KLF2 as a novel transcriptional regulator of endothelial thrombotic function. The full text of this article is available online at http://circres.ahajournals.org.
Biallelic Somatic and Germ Line
CCM1
Truncating Mutations in a Cerebral Cavernous Malformation Lesion
Authors: Gault Judith , Shenkar Robert , Recksiek Peter , Awad Issam A.
Published: February 2005

Background and Purpose—

Cerebral cavernous malformations (CCMs) are focal dysmorphic blood vessel anomalies that predispose patients to hemorrhagic stroke and epilepsy. CCMs are sporadic or inherited and 3 genes (
CCM1
,
CCM2
, and
CCM3
) have been identified. However, the role of somatic mutation in CCM genesis has been disputed. The hypothesis that somatic mutations contribute to CCM lesion genesis is tested.

Methods—

Mutations were identified by analysis of polymerase chain reaction (PCR) products spanning the 16
CCM1
coding exons with denaturing high-pressure liquid chromatography (DHPLC), cloning, and sequencing. Somatic mutation was verified 3 ways in lesion DNA and RNA samples. The somatic and germ line mutations were shown to be biallelic using allele specific reverse-transcribed PCR amplification and sequence analyses.

Results—

A somatic 34-nucleotide deletion in
CCM1
is identified in a CCM lesion along with a germ line
CCM1
mutation (Q455X). The somatic mutation is not present in DNA or RNA isolated from the patient’s blood. These 2 genetic hits are biallelic.

Conclusions—

Identification of biallelic
CCM1
somatic and germ line truncating mutations strongly support the “two-hit” mechanism in this CCM lesion.
Utility of Outcome Measures After Treatment for Intracranial Aneurysms
Authors: Kim Dong H. , Haney Charles L. , Van Ginhoven Grace
Published: February 2005

Background and Purpose—

As different intracranial aneurysm treatments are compared in upcoming trials, complete characterization of patient outcomes will be critical. Currently, graded scales such as the Glasgow Outcome Score (GOS) or the Rankin scale are commonly used. Our objective was to test the utility of different outcome instruments in patients after aneurysm treatment.

Methods—

A prospective trial comparing 6 outcome instruments at 3 to 12 months after aneurysm treatment: the Rankin and GOS, the Barthel Index (activities of daily living), the National Institutes of Health Stroke Score (NIHSS) (neurological examination), the Short Form-36 (subjective experience of recovery), and the Mini-Mental Status Examination (MMSE) (cognitive recovery). All tests were administered to each patient at the same time by an independent grader. The Spearman correlation coefficient was calculated between instruments (with 1 representing complete correlation).

Results—

In 4 years, 520 patients with 618 ruptured or unruptured aneurysms were enrolled: 385 surviving patients were tested. The resulting scores showed a wide distribution for the MMSE and the SF-36, but almost no variability for the Barthel Index and NIHSS. Correlations between scores were poor: 0.15 when the GOS was compared with the MMSE; 0.27 compared with the SF-36. Many patients given the highest GOS or Rankin scores showed significant cognitive deficits.

Conclusions—

These data indicate that a single graded scale does not address all aspects of recovery after aneurysm treatment, particularly cognitive dysfunction and the patient’s perception of health. The implications of these findings are discussed.
An Interview with Morteza Momayez
Authors: Sarmast Shahriar
Published: February 2005

Design Issues is pleased to publish this interview with Iranian graphic designer Morteza Momayez recently conducted in Tehran by Shahriar Sarmast. Morteza Momayez, Iran's foremost graphic designer, has been active in the field for more than fifty years. When he began his career in the early 1950s, he designed Iranian newspapers and magazines. In the 1960s, he completed a degree in art at the University of Tehran, and did further studies in Paris. Mr. Momayez is the author of numerous books on graphic design in Farsi, and his work was featured by F.H.K. Henrion in his book Top Graphic Design (1983). Shahriar Sarmast is an art director in Tehran, and currently is Secretary of the Iranian Graphic Designers Society. Mr. Sarmast created the cover for the Summer 2002 (XVIII: 3) of Design Issues.
Gender Differences in Cambodian Delinquency: The Role of Ethnic Identity, Parental Discipline, and Peer Delinquency
Authors: Go Charles G. , Le Thao N.
Published: February 2005

Contrary to the model minority stereotype, Asian youth are increasingly becoming more involved in crime and delinquency. For instance, in the California Youth Authority, Southeast Asian adolescents are disproportionately represented, including Cambodian, Hmong, and Lao and Mien youth. However, few studies have focused on factors that are associated with Southeast Asian adolescent delinquency. Using a Cambodian adolescent sample, this study found significant gender similarities as well as differences. In both groups, peer delinquency was significantly associated with juvenile delinquency. However, for males, ethnic identity search was also a significant factor whereas for females, parental discipline was significant. These findings argue for the need to consider gender differences in conducting research and intervention programs for Cambodians and generally, for Southeast Asian adolescents. These results also suggest a need for more research, not only with respect to gender differences, but also on how they are similar to their Southeast Asian, Asian, and U.S. counterparts.
Responding to Asian Pacific Islander Youth Violence: Lessons Learned From a Community Mobilization Strategy
Authors: Lai Mary H.
Published: February 2005

Youth violence in Asian Pacific Islander (API) communities is growing at an alarming rate as a result of many factors, such as immigration history, intergenerational conflicts, mental health and substance abuse problems, and socioeconomic context. Unfortunately, the issues of API youth are often ignored due to their small population and a general lack of understanding of this group. This article describes a federally funded, API community mobilization effort to prevent youth violence in Oakland, California. Literature is briefly summarized, followed by descriptions of the history, context, process, and outcomes of the community mobilization—a process called the Community Response Plan.
Deporting Cambodian Refugees: Justice Denied?
Authors: Hing Bill Ong
Published: February 2005

Until recently, the United States did not deport refugees convicted of crimes to the communist-dominated countries of Cuba, Vietnam, Laos, and Cambodia. After all, these refugees had fled persecution, and diplomatic ties between the United States and these countries are not particularly strong. But in March 2002, the United States convinced Cambodia to each month accept the repatriation of a few of its nationals who have been convicted of aggravated felonies. These individuals have served their sentences in the criminal justice system, and the vast majority either fled the killing fields of Cambodia as toddlers or were born in Thai refugee camps. Is justice really being served by their deportation?
The Influence of Parents, Peer Delinquency, and School Attitudes on Academic Achievement in Chinese, Cambodian, Laotian or Mien, and Vietnamese Youth
Authors: Chang Janet , Le Thao N.
Published: February 2005

Past research on academic achievement has tended to overlook the diversity among Asian American groups and the educational and socioeconomic difficulties that many Asians, particularly Southeast Asians, face. The present study addressed several shortcomings of past research by contrasting parent attachment and discipline, peer delinquency, and school attitudes as predictors of self-reported grade point average in 329 Chinese, Cambodian, Laotian or Mien, and Vietnamese youth. Results revealed that parental factors generally did not contribute much explanatory power and that school attitudes may mediate the relationship between peer delinquency and academic achievement. Interventions aimed at promoting positive adjustment and school outcomes should focus on the role of delinquent peer affiliations and youth’s attitudes toward school.
The Relationship of School, Parent, and Peer Contextual Factors with Self-Reported Delinquency for Chinese, Cambodian, Laotian or Mien, and Vietnamese Youth
Authors: Le Thao N. , Monfared Golnoush , Stockdale Gary D.
Published: February 2005

The study of delinquency has focused on examining the relative predictive value of school, parent, and peer contextual variables, but relatively little research has included Chinese and Southeast Asian youth. Using data from a larger, community-based research study with 329 Chinese, Cambodian, Laotian or Mien, and Vietnamese youth, the authors found that peer delinquency was the strongest predictor of self-reported delinquency. However, its predictive power for the Chinese group is about one half that of the other groups. School attachment negatively predicted delinquency for Chinese and Vietnamese and for males and females but not for Cambodian and Laotian or Mien. Parent Attachment and parent discipline were found to be nonsignificant predictors. LISREL analyses also indicated measurement and structural invariance across ethnic groups, providing support for cross-cultural comparisons. Implications for interventions are discussed.
Post-Traumatic Stress Disorder (PTSD)
Authors: Flouri Eirini
Published: February 2005

This article discusses the biomedical and the social constructionist models applied to response to trauma, presents the prevalence and the etiology of post-traumatic stress disorder (PTSD), and describes its biological and psychological correlates in children and adults. It concludes that future research might benefit from investigating factors that may protect people who have been exposed to an event likely to be traumatic from presenting with PTSD symptoms, and factors that may affect the longitudinal course of PTSD and treatment effectiveness.
Youth Violence in Everyday Life
Authors: Marcus Robert F.
Published: February 2005

What we now know about violence in the United States is that it is a common occurrence and recurrence for youth. Self-report methods have greatly enhanced our understanding of interpersonal violence. Specifically, from the 1980s to the present the age group most vulnerable to violence is youth. In addition, and in any given year, one third will physically fight with peers, more than one third physically fight with dating partners, and a majority of those who fight with either peers or partners will repeat this at least one more time.
Domestic Violence Research
Authors: Stover Carla Smith
Published: February 2005

Domestic violence has been an intense area of study in recent decades. Early studies helped with the understanding of the nature of perpetration, the cycle of violence, and the effect of family violence on children. More recently, studies have focused on beginning to evaluate domestic violence interventions and their effects on recidivism. This article acknowledges the importance of what we have learned about the prevalence and impact of domestic violence and explores the need for more focused effort to pinpoint interventions that are effective with perpetrators and victims. Methodological issues relevant to past intervention studies are also discussed and future research directions are outlined.
Does Childhood Sexual Abuse Set in Motion a Cycle of Violence Against Women?
Authors: Noll Jennie G.
Published: February 2005

This article reviews evidence for the deleterious effects of childhood sexual abuse on female development in both the acute and long-term phases. Taken in aggregate, there is evidence to suggest a persistent cycle of violence perpetrated against women that begins in childhood in the form of sexual abuse, reemerges later in adolescence and early adulthood in the form of physical assault or sexual revictimization, and ultimately places the next generation at considerable risk for victimization. The differential effect of the characteristics of sexual abuse and the wide variation in the onset and developmental course of symptoms are underscored. The need for adequate models elucidating mechanisms behind this continued cycle of violence is discussed.