bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Microcone Array for Antireflection Structured Surface Using Metal Dotted Pattern
Authors: Toyota Hiroshi , Takahara Koji , Okano Masato , Yotsuya Tsutom , Kikuta Hisao
Published: October 2002

An antireflection surface with sub-wavelength structure has been successfully fabricated on a fused silica substrate. The fabricated antireflection structured surface consists of a microcone array of fused silica with a period shorter than the wavelengths of visible light. The microcone array is made by a reactive ion etching method using fluorocarbon plasma. A microdisk array of chromium thin film, formed by an electron-beam lithography and lift-off process, is used as the etching mask. Since an electric field induced near the substrate was focused on the edges of the metal disks, these disks gradually shrank. Consequently, a conical shape was formed. The fabricated cone array has a period of 250 nm and a height of 750 nm. Measured reflectivity of the antireflection structured surface is less than 0.5% in the wavelength range of 400–800 nm for normal incidence.
Hyperthermal Beam for Oxidation and Nitridation Produced by Laser Evaporation of Mixed O3/N2O Cryogenic Film
Authors: Nishiguchi Tetsuya , Morikawa Yoshiki , Miyamoto Masaharu , Nonaka Hidehiko , Ichimura Shingo
Published: October 2002

We have performed KrF pulsed-laser evaporation of a cryogenic film consisting of a mixture of ozone (O3) and nitrous oxide (N2O) to obtain an energetically reactive beam for oxidation as well as nitrogen (N) incorporation. The ejection of hyperthermal nitric oxide (NO) molecules as well as hyperthermal oxygen (O) atoms and N2O molecules was observed at a relatively high laser fluence. The generation of additional NO molecules is explained by the chemical reaction between O atoms in the electronically excited state, which are generated from photodissociation of O3, and surrounding N2O molecules during the evaporation process. By applying this beam to Si, we have achieved an extremely high oxidation rate and 4–7 at.% N incorporation even at room temperature.
Monolithic White Light Emitting Diodes Based on InGaN/GaN Multiple-Quantum Wells
Authors: Damilano Benjamin , Grandjean Nicolas , Pernot Cyril , Massies Jean
Published: October 2002

Light emitting diodes (LEDs) based on In
x
Ga1-x
N (x=0.15–0.2)/GaN multiple-quantum wells (MQWs) have been grown on sapphire substrates. Their wavelength emission can be tuned from blue to orange by increasing the QW thickness. This opens the way for monolithic white LEDs by combining several QWs of various thicknesses, i.e., “colors”, inside the GaN p-n junction. This is demonstrated by the realization of white (blue+yellow) dual color LEDs. The coordinates in the CIE 1931 chromaticity diagram of the EL spectrum are (x=0.29, y=0.31) and correspond to a color temperature of 8000 K. The expected performances of the monolithic white LEDs are compared to hybrid technologies such as blue LEDs pumping yellow phosphors.
Effect of Structural Changes on the Microwave Dielectric Properties of Ba(Zn1/3Nb2/3)O3Ceramics
Authors: Noh Si-Yoon , Yoo Myong-Jae , Nahm Sahn , Choi Chang-Hak , Park Hyun-Min , Lee Hwack-Joo
Published: October 2002

The microstructure and microwave dielectric properties of Ba(Zn1/3Nb2/3)O3(BZN) ceramics have been investigated. BZN has a 1:2 ordered hexagonal structure, and the degree of 1:2 ordering decreased with increasing sintering temperature. Liquid phase was found for the BZN sintered at more than 1350°C, the evaporation of ZnO was responsible for the formation of liquid phase. BaNb6O16second phase was also found for the specimens sintered at more than 1350°C and the liquid phase is considered to have a composition close to that of BaNb6O16second phase. TheQ-value of BZN was increased with increasing sintering temperature and BZN sintered at 1400°C for 6 h has the maximumQ-value. Since the 1:2 ordering decreased with the sintering temperature, the enhancement ofQ-value is not related to the 1:2 ordering. The increase of the average grain size could be responsible for the increase of theQ-value, and the relative density also influenced theQ-value. BZN ceramics were sintered for various times at 1400°C and 1300°C and the variation ofQ-value was explained in terms of the grain size and the relative density.
Ultra-Compact HII Regions and Massive Star Formation
Authors: Churchwell Ed
Published: October 2002

▪ Abstract  This review discusses three main topics: evolution to the ultra-compact (UC) state; the properties of UC HII regions and their environments; and UC HII regions as probes of Galactic structure. The evolution to UC HII regions begins in giant molecular clouds that provide the natal material for prestellar cores that evolve into hot cores, the precursors of UC HII regions. The properties of each evolutionary phase are reviewed, with particular emphasis on those of hot cores. The observed properties of UC HII regions and their environments are summarized with emphasis on the physical processes that may produce the observed properties. The final section summarizes the use of UC HII regions as probes of Galactic structure: in particular, the Galactic population and distribution of newly formed massive stars, the location of spiral arms, and the average galactocentric temperature and abundance gradients.
RISK ASSESSMENT OF VIRUS-RESISTANT TRANSGENIC PLANTS
Authors: Tepfer Mark
Published: October 2002

▪ Abstract  Virus-resistant transgenic plants (VRTPs) hold the promise of enormous benefit for agriculture. However, over the past ten years, questions concerning the potential ecological impact of VRTPs have been raised. In some cases, detailed study of the mode of action of the resistance gene has made it possible to eliminate the source of potential risk, notably the possible effects of heterologous encapsidation on the transmission of viruses by their vectors. In other cases, the means of eliminating likely sources of risk have not yet been developed. When such residual risk still exists, the potential risks associated with the VRTP must be compared with those associated with nontransgenic plants so that risk assessment can fully play its role as part of an overall analysis of the advantages and disadvantages of practicable solutions to the problem solved by the VRTP.
VIRAL SEQUENCES INTEGRATED INTO PLANT GENOMES
Authors: Harper Glyn , Hull Roger , Lockhart Ben , Olszewski Neil
Published: October 2002

▪ Abstract  Sequences of various DNA plant viruses have been found integrated into the host genome. There are two forms of integrant, those that can form episomal viral infections and those that cannot. Integrants of three pararetroviruses, Banana streak virus (BSV), Tobacco vein clearing virus (TVCV), and Petunia vein clearing virus (PVCV), can generate episomal infections in certain hybrid plant hosts in response to stress. In the case of BSV and TVCV, one of the parents contains the integrant but is has not been seen to be activated in that parent; the other parent does not contain the integrant. The number of integrant loci is low for BSV and PVCV and high in TVCV. The structure of the integrants is complex, and it is thought that episomal virus is released by recombination and/or reverse transcription. Geminiviral and pararetroviral sequences are found in plant genomes although not so far associated with a virus disease. It appears that integration of viral sequences is widespread in the plant kingdom and has been occurring for a long period of time.
GENEEXPRESSION INNEMATODEFEEDINGSITES
Authors: Gheysen Godelieve , Fenoll Carmen
Published: October 2002

▪ Abstract  The feeding sites induced by sedentary root–endoparasitic nematodes have long fascinated researchers. Nematode feeding sites are constructed from plant cells, modified by the nematode to feed itself. Powerful new techniques are allowing us to begin to elucidate the molecular mechanisms that produce the ultrastructural features in nematode feeding cells. Many plant genes that are expressed in feeding sites produced by different nematodes have been identified in several plant species. Nematode-responsive plant genes can now be grouped in categories related to plant developmental pathways and their roles in the making of a feeding site can be illuminated. The black box of how nematodes bring about such elaborate cell differentiation in the plant is also starting to open. Although the information is far from complete, the groundwork is set so that the functions of the plant and nematode genes in feeding site development can begin to be assessed.
Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin
Authors: Majors Alana K. , Sengupta Shantanu , Willard Belinda , Kinter Michael T. , Pyeritz Reed E. , Jacobsen Donald W.
Published: October 2002

Objective—

More than 70% of circulating homocysteine is disulfide-bonded to protein, but little is known about the specific proteins that bind homocysteine and their function as a consequence of homocysteine binding.

Methods and Results—

When human plasma was incubated with [
35
S]
l
-homocysteine, most of the homocysteine bound to albumin. However, additional homocysteine-binding proteins were detected, and 1 of them comigrated with fibronectin. Treatment with 2-mercaptoethanol removed the bound homocysteine, demonstrating the involvement of disulfide bonding. In contrast, [
35
S]
l
-cysteine did not bind to fibronectin. Purified fibronectin bound ≈5 homocysteine molecules per fibronectin dimer. SDS-PAGE of a limited trypsin digestion of homocysteinylated fibronectin showed that several tryptic fragments contained [
35
S]homocysteine. Sequence analysis demonstrated that the fragments containing bound homocysteine had localized mainly to the C-terminal region, within and adjacent to the fibrin-binding domain. Homocysteinylation of fibronectin significantly inhibited its capacity to bind fibrin by 62% (
P
<0.005). In contrast, neither the binding of fibronectin to gelatin nor its capacity to serve as an attachment factor for aortic smooth muscle cells was affected.

Conclusions—

These results suggest that homocysteine may alter normal thrombosis and delay or interfere with wound healing by impairing the interaction of fibronectin with fibrin.
Inflammation in Atherosclerosis
Authors: Schiller Natalie K. , Boisvert William A. , Curtiss Linda K.
Published: October 2002

Objective—Natural killer (NK) cells have been identified in human vascular pathologies. In this study, we identified NK cells in aortic root atherosclerotic lesions of low density lipoprotein (LDL) receptor–deficient (LDLr−/−) mice. To characterize the role of NK cell–mediated cytolysis in atherosclerosis, we generated C57Bl/6 double-mutant mice by crossing LDLr−/− mice with NK cell–defectiveLystbeigemice (creating beige,LDLr−/− mice) and with perforin-deficient mice (creating Pfp−/−,LDLr−/− mice).

Methods and Results—Male mice (8 to 10 weeks old) were fed a high-fat diet to induce atherosclerosis. Compared with LDLr−/− mice, beige,LDLr−/− mice had impaired NK cell cytolytic activity and significantly increased atherosclerosis (P<0.05). Pfp−/−,LDLr−/− mice had impaired NK cell cytolytic activity, yet they had lesions that were similar to those of control mice. This suggested that NK cell cytolysis did not play a significant role in atherosclerosis and that the exacerbated atherosclerosis of the beige,LDLr−/− mouse was independent of impaired NK cell cytolytic activity. Therefore, we investigated the role of T and B lymphocytes in atherosclerosis of beige mice by crossing them with recombinase activator gene 1–deficient LDLr−/− mice (Rag1−/−,LDLr−/− mice), thus creating beige,Rag1−/−, LDLr−/− mice. As in the double-mutant study, beige,Rag1−/−,LDLr−/− mice had significantly increased lesions compared with Rag1−/−,LDLr−/− control mice.

Conclusions—Therefore, theLystbeigemutation in LDLr−/− mice has proatherogenic properties that are independent of NK cell–mediated cytolysis and lymphocyte-mediated acquired immunity.
Cholesteryl Ester Transfer Protein Expressed in Lecithin Cholesterol Acyltransferase–Deficient Mice
Authors: Wu Cheng-ai , Tsujita Maki , Okumura-Noji Kuniko , Usui Shinichi , Kakuuchi Hajime , Okazaki Mitsuyo , Yokoyama Shinji
Published: October 2002

Objective—

Regulation of plasma cholesteryl ester transfer protein (CETP) concentration was studied in lecithin-cholesterol acyltransferase (LCAT)-knockout mice.

Methods and Results—

LCAT-knockout mice were cross-bred with CETP transgenic mice. The offspring (n=63) were classified for LCAT genotype and plasma CETP levels (no CETP, low CETP, and high CETP). High density lipoprotein (HDL) decreased as LCAT decreased in each CETP-level group. In the
lcat(+/+)
and
lcat(+/
−
)
mice, plasma CETP varied from 0 to 30 μg/mL, whereas it was <10 μg/mL in the
lcat(
−
/
−
)
mice. HDL cholesterol and phospholipid decreased and HDL triglyceride and apolipoprotein B increased in CETP in the
lcat(+/+)
and
lcat(+/
−
)
mice, whereas there was no difference in HDL between low and high CETP. An effect of CETP on HDL was not detected in the
lcat(
−
/
−
)
mice because of the absence of mature HDL. Genomic DNA and mRNA of CETP were correlated and were similar in the
lcat(
−
/
−
)
and
lcat(+/+)
mice. Plasma CETP was correlated with its genomic DNA and mRNA, but the slope of the increase was much lower in the
lcat(
−
/
−
)
mice. Whereas plasma CETP mostly associates with HDL in the
lcat(+/+)
mouse, it is found free in the
lcat(
−
/
−
)
mouse.

Conclusions—

Plasma CETP is posttranscriptionally downregulated in the
lcat(
−
/
−
)
mice, presumably by its extremely low HDL.
Impaired Myocardial Fatty Acid Oxidation and Reduced Protein Expression of Retinoid X Receptor-α in Pacing-Induced Heart Failure
Authors: Osorio Juan Carlos , Stanley William C. , Linke Axel , Castellari Michele , Diep Quy N. , Panchal Ashish R. , Hintze Thomas H. , Lopaschuk Gary D. , Recchia Fabio A.
Published: October 2002

Background

—

The nuclear receptors peroxisome proliferator-activated receptor-α (PPARα) and retinoid X receptor α (RXRα) stimulate the expression of key enzymes of free fatty acid (FFA) oxidation. We tested the hypothesis that the altered metabolic phenotype of the failing heart involves changes in the protein expression of PPARα and RXRα.

Methods and Results

—

Cardiac substrate uptake and oxidation were measured in 8 conscious, chronically instrumented dogs with decompensated pacing-induced heart failure and in 8 normal dogs by infusing 3 isotopically labeled substrates:
3
H-oleate,
14
C-glucose, and
13
C-lactate. Although myocardial O
2
consumption was not different between the 2 groups, the rate of oxidation of FFA was lower (2.8±0.6 versus 4.7±0.3 μmol · min
−1
· 100g
−1
) and of glucose was higher (4.6±1.0 versus 1.8±0.5 μmol · min
−1
· 100g
−1
) in failing compared with normal hearts (
P
<0.05). The rates of lactate uptake and lactate output were not significantly different between the 2 groups. In left ventricular tissue from failing hearts, the activity of 2 key enzymes of FFA oxidation was significantly reduced: carnitine palmitoyl transferase-I (0.54±0.04 versus 0.66±0.04 μmol · min
−1
· g
−1
) and medium chain acyl-coenzyme A dehydrogenase (MCAD; 1.8±0.1 versus 2.9±0.3 μmol · min
−1
· g
−1
). Consistently, the protein expression of MCAD and of RXRα were significantly reduced by 38% in failing hearts, but the expression of PPARα was not different. Moreover, there were significant correlations between the expression of RXRα and the expression and activity of MCAD.

Conclusions

—

Our results provide the first evidence for a link between the reduced expression of RXRα and the switch in metabolic phenotype in severe heart failure.
Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits
Authors: Danenberg Haim D. , Fishbein Ilia , Gao Jianchuan , Mönkkönen Jukka , Reich Reuven , Gati Irith , Moerman Evgeny , Golomb Gershon
Published: October 2002

Background

—

Inflammation is critical to vascular repair after mechanical injury. Excessive inflammation enhances neointimal formation and restenosis. We examined whether transient systemic inactivation of macrophages at the time of vascular intervention could attenuate the degree of expected restenosis.

Methods and Results

—

Liposomal clodronate (LC) inhibited the growth of cultured macrophages but had no effect on endothelial or smooth muscle cells and suppressed neointimal hyperplasia in hypercholesterolemic rabbits and rats after intravenous administration of LC, with no adverse effects. LC treatment reduced the number of blood monocytes and decreased macrophage infiltration in the injured arteries as well as smooth muscle cell proliferation, interleukin-1β transcription, and production and matrix metalloproteinase-2 activity.

Conclusions

—

Macrophages play a pivotal role in vascular repair after mechanical arterial injury. Systemic inactivation and depletion of monocytes and macrophages by LC reduce neointimal hyperplasia and restenosis.
Assessment of Myocardial Inflammation Produced by Experimental Coronary Occlusion and Reperfusion With
99m
Tc-RP517, a New Leukotriene B4 Receptor Antagonist That Preferentially Labels Neutrophils In Vivo
Authors: Riou Laurent M. , Ruiz Mirta , Sullivan Gail W. , Linden Joel , Leong-Poi Howard , Lindner Jonathan R. , Harris Thomas D. , Beller George A. , Glover David K.
Published: October 2002

Background

—

99m
Tc-RP517 is a new leukotriene B
4
(LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of
99m
Tc-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative
99m
Tc-RP517 binding to human leukocyte subtypes and the
99m
Tc-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor α (TNFα) injection.

Methods and Results

—

Fluorescence-activated cell sorter analysis was performed on whole human blood (n=2) and isolated neutrophils (n= 4) with a fluorescent analog of
99m
Tc-RP517, [F]-RP517. In whole blood, [F]-RP517 (500 nmol/L) preferentially labeled neutrophils. On isolated neutrophils, [F]-RP517 (10 nmol/L) binding was inhibited by 44% when LTB4 (400 nmol/L) was added.
99m
Tc-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlusion (90 minutes) and reperfusion (120 minutes) (n=9) or before intramyocardial TNFα injection (n=3). Ex vivo images of heart slices were acquired. The left ventricle was divided into 72 segments for flow and
99m
Tc-RP517 uptake analysis. There was an inverse exponential relationship between
99m
Tc-RP517 uptake and occlusion flow (
r
=0.73). In the same 15 segments,
99m
Tc-RP517 uptake was highly correlated with the neutrophil enzyme myeloperoxidase (
r
=0.91). Ex vivo images revealed tracer uptake in the reperfused area (ischemic to normal count ratio=2.7±0.2).

Conclusions

—

RP517 binds to the neutrophil LTB4 receptor after intravenous injection. After reperfusion,
99m
Tc-RP517 uptake correlated with myeloperoxidase and was observed on ex vivo images, indicating that this tracer may have potential as an inflammation-imaging agent.
Fetal Cardiomyopathies
Authors: Pedra Simone R.F.F. , Smallhorn Jeffrey F. , Ryan Greg , Chitayat David , Taylor Glenn P. , Khan Rubina , Abdolell Mohamed , Hornberger Lisa K.
Published: October 2002

Background

—

Although the prenatal diagnosis of most fetal structural heart defects and dysrhythmias has been described, there is a paucity of information about cardiomyopathies (CMs) in prenatal life.

Methods and Results

—-

To determine the pathogenic mechanisms, hemodynamic findings, and outcome of fetal CM, we reviewed the fetal echocardiograms and perinatal histories of 55 affected fetuses. Dilated CM was diagnosed in 22 cases, including 2 with congenital infections, 5 familial cases, 6 with endocardial fibroelastosis related to maternal anti-Ro/La antibodies, and 9 idiopathic cases. Thirty-three had hypertrophic CM, 7 associated with maternal diabetes, 2 with Noonan’s syndrome, 2 with α-thalassemia, 18 with twin-twin transfusion syndrome, 1 with familial hypertrophy, and 3 with idiopathic hypertrophy. Systolic dysfunction was present in all cases of dilated CM and 15 cases of hypertrophic CM. Diastolic dysfunction was present in 19 of 30 fetuses with assessment of diastolic function parameters. Significant mitral or tricuspid valve regurgitation was seen in 32 cases. Eight fetuses were hydropic and 23 had signs of early hydrops. Seven pregnancies were terminated. Of 46 continued pregnancies with follow-up, 29 (63%) died perinatally. The presence of systolic dysfunction, diastolic dysfunction, and significant atrioventricular valve regurgitation were identified as risk factors for mortality. By multiple logistic regression, diastolic dysfunction was associated with an 8-fold increased risk relative to the other parameters.

Conclusions

—

Fetal CM has a broad spectrum of intrinsic and extrinsic causes. A poor outcome is observed in many affected fetuses. Diastolic dysfunction in fetal CM is associated with the highest risk of mortality.
Mitochondrial Integrity and Function in Atherogenesis
Authors: Ballinger Scott W. , Patterson Cam , Knight-Lozano Cynthia A. , Burow David L. , Conklin Caryl A. , Hu Zhaoyong , Reuf Johannes , Horaist Chris , Lebovitz Russell , Hunter Glenn C. , McIntyre Ken , Runge Marschall S.
Published: October 2002

Background

—

Coronary atherosclerotic disease remains the leading cause of death in the Western world. Although the exact sequence of events in this process is controversial, reactive oxygen and nitrogen species (RS) likely play an important role in vascular cell dysfunction and atherogenesis. Oxidative damage to the mitochondrial genome with resultant mitochondrial dysfunction is an important consequence of increased intracellular RS.

Methods and Results

—

We examined the contribution of mitochondrial oxidant generation and DNA damage to the progression of atherosclerotic lesions in human arterial specimens and atherosclerosis-prone mice. Mitochondrial DNA damage not only correlated with the extent of atherosclerosis in human specimens and aortas from apolipoprotein E
−/−
mice but also preceded atherogenesis in young apolipoprotein E
−/−
mice. Apolipoprotein E
−/−
mice deficient in manganese superoxide dismutase, a mitochondrial antioxidant enzyme, exhibited early increases in mitochondrial DNA damage and a phenotype of accelerated atherogenesis at arterial branch points.

Conclusions

—

Mitochondrial DNA damage may result from RS production in vascular tissues and may in turn be an early event in the initiation of atherosclerotic lesions.
Twelve Versus Six Months of Clopidogrel to Reduce Major Cardiac Events in Patients Undergoing γ-Radiation Therapy for In-Stent Restenosis
Authors: Waksman Ron , Ajani Andrew E. , Pinnow Ellen , Cheneau Edouard , Leborgne Laurent , Dieble Regina , Bui Anh B. , Satler Lowell F. , Pichard Augusto D. , Kent Kenneth K. , Lindsay Joseph
Published: October 2002

Background—

Intracoronary γ-radiation reduces recurrent in-stent restenosis (ISR). Late thrombosis was attenuated with 6 months of aspirin and clopidogrel. We aimed to find out whether 12 months of aspirin plus clopidogrel is superior to a strategy of 6 months after radiation therapy for patients with ISR.

Methods and Results—

One hundred twenty consecutive patients with diffuse ISR in native coronaries and vein grafts with lesions <80 mm in length underwent PTCA, laser ablation, or rotational atherectomy. Additional stents were placed in 39 patients (33%). After the intervention, a ribbon with different trains of radioactive
192
Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 12 months and followed up clinically. The cardiac clinical event rates at 15 months were compared with the γ-treated (n=120) patients of the WRIST PLUS study (only 6 months of antiplatelet therapy). Whereas the late thrombosis rates were similar (3.3% for the group given 12 months of antiplatelet therapy versus 4.2% for the group given 6 months,
P
=0.72), the group treated with 12 months of antiplatelet therapy had a rate of 21% for major adverse cardiac events and 20% for target-lesion revascularization compared with 36% (
P
=0.01) and 35% (
P
=0.009), respectively, in patients who were treated with only 6 months of clopidogrel.

Conclusions—

Twelve months of clopidogrel is superior to 6 months in reducing overall major cardiac events and revascularization rates at 15 months for patients with ISR treated with γ-radiation. At least 12 months of clopidogrel therapy should be recommended for patients undergoing radiation therapy for ISR.
High Rate of Ventricular Septal Defects in WKY Rats
Authors: Slama Michel , Susic Dinko , Varagic Jasmina , Frohlich Edward D.
Published: October 2002

In 1979, we first reported occurrence of biventricular hypertrophy in the original normotensive Wistar-Kyoto (WKY) strain obtained from the National Heart, Lung, and Blood Institute, which was derived directly from the Kyoto laboratory of Okamoto. At that time, we recommended that both ventricles be weighted when WKY are studied so that invalid conclusions are not made. Because no paper confirmed these findings for almost 20 years, heart weights were reported in only a few WKY studies, and the cause of this biventricular hypertrophy remained unknown, we re-evaluated this problem in commercially available rats. We, therefore, investigated WKY rats using transthoracic echocardiography to define the congenital heart defect. Up to 28% of commercially available WKY rats demonstrated severe congenital cardiac abnormalities associated with biventricular hypertrophy. Ventricular septal defect with pulmonary regurgitation was the most commonly encountered cardiac defect; other abnormalities included patent ductus arteriosus, and valvular defects. Pathologic and invasive hemodynamic studies confirmed these echocardiographic findings. Because this defect occurs in a large number of WKY rats obtained commercially from 2 different sources, investigators using this strain must carefully measure both ventricular weights to be certain that inappropriate and invalid conclusions are not derived therefrom.
AT
1
Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats
Authors: Nagata Kohzo , Somura Fuji , Obata Koji , Odashima Mari , Izawa Hideo , Ichihara Sahoko , Nagasaka Tetsuro , Iwase Mitsunori , Yamada Yoshiji , Nakashima Nobuo , Yokota Mitsuhiro
Published: October 2002

The possible role of calcineurin in the attenuation of cardiac hypertrophy and fibrosis by blockade of the angiotensin II type 1 (AT
1
) receptor was investigated in Dahl salt-sensitive (DS) rats. The effect of the calcineurin inhibitor FK506 was also studied. DS rats progressively developed severe hypertension when fed a diet containing 8% NaCl from 7 weeks of age. In addition, marked cardiac hypertrophy and fibrosis were apparent and the activity of calcineurin and its mRNA expression in the myocardium was increased in these animals at 12 weeks in comparison with age-matched Dahl salt-resistant rats. The abundance of angiotensin-converting enzyme (ACE) and transforming growth factor (TGF)-β1 mRNAs was also increased in the hearts of DS rats at 12 weeks. Treatment of DS rats with a non-antihypertensive dose of the selective AT
1
receptor blocker candesartan (1 mg/kg per day) or FK506 (0.1 mg/kg per day) from 7 to 12 weeks attenuated both calcineurin activity and its mRNA expression in the heart, as well as the development of cardiac hypertrophy and fibrosis, without affecting cardiac function. Treatment with candesartan, but not FK506, prevented the upregulation of ACE and TGF-β1 gene expression. Both candesartan and FK506 prevented the load-induced induction of fetal-type cardiac genes. These results demonstrate that AT
1
receptor blockade attenuates the development of cardiac hypertrophy and fibrosis as well as the activation of calcineurin, without an antihypertensive effect, in rats with salt-sensitive hypertension. Calcineurin may be downstream from TGF-β1 in AT
1
receptor-mediated angiotensin II signaling in vivo.
Cardiac Septation
Authors: Lamers Wouter H. , Moorman Antoon F.M.
Published: October 2002

Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4 and 7 weeks of development. Cardiac looping and chamber formation bring the contributing structures into position to engage in septation. Cardiomyocytes that participate in chamber formation do not materially contribute to septation. The (re)discovery of the role of extracardiac mesenchymal tissue in atrioventricular septation, the appreciation that the formation of the right atrioventricular connection is more than a mere rightward expansion of the atrioventricular canal, the awareness that myocardium originating from the so-called anterior heart field regresses after its function as outflow-tract sphincter ceases, and the recent finding that the myocardialized proximal portion of the outflow-tract septum becomes the supraventricular crest have all significantly enhanced our understanding of the morphogenetic processes that contribute to septation. The bifurcation of the ventricular conduction system is the landmark that separates the contribution of the atrioventricular cushions and the outflow-tract ridges to septation and that divides the muscular ventricular septum in inlet, trabecular, and outlet portions.
Cardiac Dysfunction in Hypertrophic Cardiomyopathy Mutant Tropomyosin Mice Is Transgene-Dependent, Hypertrophy-Independent, and Improved by β-Blockade
Authors: Michele Daniel E. , Gomez Carlen A. , Hong Katie E. , Westfall Margaret V. , Metzger Joseph M.
Published: October 2002

Familial hypertrophic cardiomyopathy (FHC) has been linked to mutations in proteins of the cardiac contractile apparatus, including α-tropomyosin (Tm). Mice expressing αTm in the heart were developed to determine the effects of FHC mutant Tm on cardiac structure and function from single cardiac myocytes to whole organ function in vivo. Expression of E180G mutant Tm did not produce cardiac hypertrophy or detectable changes in cardiac muscle morphology. However, E180G mutant Tm expression increased the Ca
2+
sensitivity of force production in single cardiac myocytes in a transgene expression–dependent manner. Contractile dysfunction in single myocytes manifested organ level dysfunction, as conductance-micromanometry showed E180G Tm mice had significantly slowed relaxation (diastolic dysfunction) under physiological conditions. The diastolic dysfunction in E180G Tm mice was no longer evident during β-blockade because propranolol eliminated the effect of E180G Tm to slow myocardial relaxation. Cellular and organ level dysfunction were evident in E180G Tm mice in the absence of significant cardiac structural abnormalities normally associated with FHC. These findings therefore suggest that diastolic dysfunction in FHC may be a direct consequence of FHC mutant protein expression. In addition, because diastolic dysfunction in E180G Tm mice is dependent on inotropic status, cardiovascular stress may play an important role in FHC pathogenesis.
Transcriptional Control of Cardiac Allograft Vasculopathy by Early Growth Response Gene-1 (Egr-1)
Authors: Okada Morihito , Wang Catherine Y. , Hwang Daniel W. , Sakaguchi Taichi , Olson Kim E. , Yoshikawa Yasushi , Minamoto Kanji , Mazer Sean P. , Yan Shi-Fang , Pinsky David J.
Published: October 2002

Expression of the zinc finger transcription factor early growth response gene-1 (Egr-1) is triggered rapidly after mechanical vascular injury or after a precipitous drop in ambient oxygen, whereupon it induces the expression of diverse gene families to elicit a pathological response. Initially characterized as an early response transcriptional activator, the role of Egr-1 in more chronic forms of vascular injury remains to be defined. Studies were designed to examine whether Egr-1 induction may serve as a causal link between early preservation injury and delayed vascular consequences, such as coronary allograft vasculopathy (CAV). The preservation and transplantation of heterotopic murine cardiac allografts strongly induce Egr-1 expression, leading to increased expression of its downstream target genes, such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet-derived growth factor A chain. Expression of these Egr-1–inducible gene targets is virtually obliterated in homozygous Egr-1–null donor allografts, which also exhibit attenuated parenchymal rejection and reduced CAV as long as 60 days. Congruous data are observed by treating donor hearts with a phosphorothioate antisense oligodeoxyribonucleotide directed against Egr-1 before organ harvest, which blocks subsequent expression of Egr-1 mRNA and protein and suppresses the late development of CAV. These data indicate that Egr-1 induction represents a central effector mechanism in the development of chronic rejection characterized by CAV. Blocking the expression of this proximal transcription factor solely at the time of organ harvest elicits beneficial delayed consequences for the cardiac allograft.
Sarcolemmal K
ATP
Channel Triggers Opioid-Induced Delayed Cardioprotection in the Rat
Authors: Patel Hemal H. , Hsu Anna K. , Peart Jason N. , Gross Garrett J.
Published: October 2002

Recently, the involvement of sarcolemmal K
ATP
(sarcK
ATP
) channels in ischemic and pharmacological preconditioning (IPC and PPC) has been minimized by numerous studies suggesting a primary role for mitochondrial K
ATP
(mitoK
ATP
) channels in early and delayed cardioprotection. Although the mitoK
ATP
channel has clearly been shown to be a distal effector of delayed IPC and PPC, studies implicating it as a trigger of protection in delayed IPC are lacking. Accordingly, we characterized the role of cardiac K
ATP
channels as triggers or distal effectors of delayed cardioprotection induced by opioids in rats, and the data suggest that the sarcK
ATP
channel triggers and that the mitoK
ATP
channel is a distal effector of opioid-induced delayed cardioprotection.
α
1
-Adrenoceptor-Mediated Breakdown of Phosphatidylinositol 4,5-Bisphosphate Inhibits Pinacidil-Activated ATP-Sensitive K
+
Currents in Rat Ventricular Myocytes
Authors: Haruna Tetsuya , Yoshida Hidetada , Nakamura Tomoe Y. , Xie Lai-Hua , Otani Hideo , Ninomiya Tomonori , Takano Makoto , Coetzee William A. , Horie Minoru
Published: October 2002

Phosphatidylinositol 4,5-bisphosphate (PIP
2
) stimulates ATP-sensitive K
+
(K
ATP
) channel activity. Because phospholipase C (PLC) hydrolyzes membrane-bound PIP
2
, which in turn may potentially decrease K
ATP
channel activity, we investigated the effects of the α
1
-adrenoceptor-G
q
-PLC signal transduction axis on pinacidil-activated K
ATP
channel activity in adult rat and neonatal mouse ventricular myocytes. The α
1
-adrenoceptor agonist methoxamine (MTX) reversibly inhibited the pinacidil-activated K
ATP
current in a concentration-dependent manner (IC
50
20.9±6.6 μmol/L). This inhibition did not occur when the specific α
1
-adrenoceptor antagonist, prazosin, was present. An involvement of G proteins is suggested by the ability of GDPβS to prevent this response. Blockade of PLC by U-73122 (2 μmol/L) or neomycin (2 mmol/L) attenuated the MTX-induced inhibition of K
ATP
channel activity. In contrast, the MTX response was unaffected by protein kinase C inhibition or stimulation by H-7 (100 μmol/L) or phorbol 12,13-didecanoate. The MTX-induced inhibition became irreversible in the presence of wortmannin (20 μmol/L), an inhibitor of phosphatidylinositol-4 kinase, which is expected to prevent membrane PIP
2
replenishment. In excised inside-out patch membranes, pinacidil induced a significantly rightward shift of ATP sensitivity of the channel. This phenomenon was reversed by pretreatment of myocytes with MTX. Direct visualization of PIP
2
subcellular distribution using a PLCδ pleckstrin homology domain-green fluorescent protein fusion constructs revealed reversible translocation of green fluorescent protein fluorescence from the membrane to the cytosol after α
1
-adrenoceptor stimulation. Our data demonstrate that α
1
-adrenoceptor stimulation reduces the membrane PIP
2
level, which in turn inhibits pinacidil-activated K
ATP
channels.
Phosphoinositide 3-Kinase Mediates Enhanced Spontaneous and Agonist-Induced Contraction in Aorta of Deoxycorticosterone Acetate-Salt Hypertensive Rats
Authors: Northcott Carrie A. , Poy Matthew N. , Najjar Sonia M. , Watts Stephanie W.
Published: October 2002

Arteries from deoxycorticosterone acetate (DOCA)-salt and
N
ω
-nitro-
l
-arginine (L-NNA) hypertensive but not normotensive rats develop spontaneous tone. LY294002 and wortmannin, phosphoinositide 3-kinase (PI3-kinase) inhibitors, eliminate spontaneous tone. We hypothesized that PI3-kinase protein and/or activity was increased in hypertension and contributed to the observed enhanced contractility. PI3-kinase activity assays revealed 2-fold higher activity in thoracic aorta from DOCA-salt [systolic blood pressure (SBP)=184±5 mm Hg] compared with sham rats (SBP=111±2 mm Hg). Western analyses of aortic homogenates revealed the presence of p85α, p110α, p110β, and p110δ but not p110γ PI3-kinase subunits; p110δ protein was elevated in aorta of hypertensive rats as compared with sham. Aortic homogenates from L-NNA rats also had elevated p110β protein density, but neither L-NNA nor DOCA-salt had differences in p85α and p110α. Total Akt density was unaltered, but pAkt was significantly lower in homogenates from DOCA-salt rats. LY294002 (20 μmol/L) and nifedipine (50 nmol/L) abolished Ca
2+
-induced spontaneous tone in aorta from DOCA-salt rats. However, LY294002 did not alter BayK8644-induced contraction, indicating that LY294002 does not inhibit L-type Ca
2+
channels directly. PTEN (phosphatase and tensin homolog) and pPTEN were expressed but not different in aorta from DOCA-salt and sham rats. LY294002 corrected the enhanced contraction to KCl and norepinephrine in aorta from DOCA-salt rats. These data support an increase in PI3-kinase activity and p110δ density in aorta from L-NNA and DOCA-salt rats. Importantly, this increase contributes to the enhanced contractility observed in two models of hypertension.
Chronic Hypoxia Increases Endothelial Nitric Oxide Synthase Generation of Nitric Oxide by Increasing Heat Shock Protein 90 Association and Serine Phosphorylation
Authors: Shi Yang , Baker John E. , Zhang Chenyang , Tweddell James S. , Su Jidong , Pritchard Kirkwood A.
Published: October 2002

Chronic hypoxia increases endothelial nitric oxide synthase (eNOS) production of nitric oxide (·NO) and cardioprotection in neonatal rabbit hearts. However, the mechanism by which this occurs remains unclear. Recent studies suggest that heat shock protein 90 (hsp90) alters eNOS function. In the present study, we examined the role of hsp90 in eNOS-dependent cardioprotection in neonatal rabbit hearts. Chronic hypoxia increased recovery of postischemic left ventricular developed pressure (LVDP). Geldanamycin (GA), which inhibits hsp90 and increases oxidative stress, decreased functional recovery in normoxic and hypoxic hearts. To determine if a loss in ·NO, afforded by GA, decreased recovery, GA-treated hearts were perfused with
S
-nitrosoglutathione (GSNO) as a source of ·NO. GSNO increased recovery of postischemic LVDP in GA-treated normoxic and hypoxic hearts to baseline levels. Although chronic hypoxia decreased phosphorylated eNOS (S1177) levels by ≈4- to 5-fold and total Akt and phosphorylated Akt by 4- and 5-fold, it also increased hsp90 association with eNOS by more than 3-fold. Using hydroethidine (HEt), a fluorescent probe for superoxide, we found that hypoxic hearts contained less ethidine (Et) staining than normoxic hearts. Normoxic hearts generated 3 times more superoxide by an
N
ω
-nitro-
l
-arginine methyl ester (L-NAME)-inhibitable mechanism than hypoxic hearts. Taken together, these data indicate that the association of hsp90 with eNOS is important for increasing ·NO production and limiting eNOS-dependent superoxide anion generation. Such changes in eNOS function appear to play a critical role in protecting the myocardium against ischemic injury.
Previous and Incident Dementia as Risk Factors for Mortality in Stroke Patients
Authors: Barba Raquel , Morin Maria-del-Mar , Cemillán Carlos , Delgado Carlos , Domingo Julio , Del Ser Teodoro
Published: October 2002

Background and Purpose

—

We sought to determine whether previous or incident dementia increases the risk of mortality after stroke.

Methods

—

We assessed clinical, functional, and cognitive status in 324 consecutive stroke patients who were followed up for 24 months. Prestroke dementia was diagnosed at admission (
Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition
criteria) and poststroke dementia 3 months after stroke (
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
criteria). The proportion of patients surviving in the groups with and without dementia and the relative risk of mortality were calculated with Kaplan-Meier and with Cox proportional hazards analyses, respectively, for prestroke, stroke-related, and poststroke dementia.

Results

—

Forty-nine patients (15.1% of the total sample) were found to have prestroke dementia. Three months after stroke, 75 cases had poststroke dementia: 50 incident cases (20% of 251 reexamined cases) with stroke-related dementia and 25 already demented before the stroke. After a mean follow-up of 16.1±9.9 months, the proportion of survivors was 20.4% in patients with and 72.6% in those without prestroke dementia. After a mean follow-up of 22.1±6.7 months, the proportion of survivors was 58.3% in patients with and 95.4% in those without stroke-related dementia. Using multivariate analysis and adjusting for age, sex, hypertension, diabetes, previous stroke, heart disease, and severity and recurrence of stroke, we found the relative risk of mortality associated with prestroke dementia to be 2.1 (95% CI, 1.2 to 3.6), with stroke-related dementia 6.3 (95% CI, 2.3 to 17.3), and with poststroke d ementia 8.5 (95% CI, 3.4 to 20.9).

Conclusions

—

Both previous dementia and incident dementia adversely influence long-term survival after stroke, even after adjustment for other predictors of stroke mortality.
Prevalence and Predictors of Upper Airway Obstruction in the First 24 Hours After Acute Stroke
Authors: Turkington P.M. , Bamford J. , Wanklyn P. , Elliott M.W.
Published: October 2002

Background and Purpose

—

The prevalence of sleep-disordered breathing after stroke has been reported to be between 32% and 71%. However, the first 24-hour period, when upper airway obstruction may have a critical effect on the cerebral circulation because of hemodynamic fluctuations and repetitive hypoxia, has not been studied. Furthermore, data on prediction of upper airway obstruction after stroke are limited. This study sought to assess the prevalence of upper airway obstruction in the first 24 hours of stroke and to ascertain whether its occurrence could be predicted.

Methods

—

One hundred twenty patients with acute stroke underwent a respiratory variable-only sleep study, started within 24 hours of onset of neurological symptoms. Sleep history and stroke characteristics were recorded on admission.

Results

—

We found that 79%, 61%, and 45% of the patients had a respiratory disturbance index greater than 5, 10, and 15 events per hour, respectively. Patients had a significantly higher respiratory disturbance index when nursed in the supine (29 events per hour), supine left (29 events per hour), and supine right (24 events per hour) positions than in any other position (
P
<0.0001). On logistic regression analysis, BMI (
P
=0.025), neck circumference (
P
=0.026), and limb weakness (
P
=0.025) independently predicted the occurrence of upper airway obstruction in the first 24 hours after acute stroke.

Conclusions

—

Upper airway obstruction is common in the first 24 hours after stroke, especially if patients are nursed in the supine position, and typical obstructive sleep apnea risk factors (body mass index and neck circumference) appear to be the best predictors of its occurrence. Stroke characteristics (severity, clinical subtype, and clinically assessed pharyngeal function) are not independently associated with upper airway obstruction after stroke.
Comparison of Admission Perfusion Computed Tomography and Qualitative Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Acute Stroke Patients
Authors: Wintermark M. , Reichhart M. , Cuisenaire O. , Maeder P. , Thiran J.-P. , Schnyder P. , Bogousslavsky J. , Meuli R.
Published: October 2002

Background and Purpose

—

Besides classic criteria, cerebral perfusion imaging could improve patient selection for thrombolytic therapy. The purpose of this study was to compare quantitative perfusion CT imaging and qualitative diffusion- and perfusion-weighted MRI (DWI and PWI) in acute stroke patients at the time of their emergency evaluation.

Methods

—

Thirteen acute stroke patients underwent perfusion CT and DWI or PWI on admission. The size of infarct and ischemic lesion (infarct plus penumbra) on the admission perfusion CT was compared with that of the MR abnormalities as shown on the DWI trace and on the relative cerebral blood volume, cerebral blood flow, time to peak, and mean transit time maps calculated from PWI studies.

Results

—

The most significant correlation was found between infarct size on the admission perfusion CT and abnormality size on the admission DWI map (
r
=0.968,
P
<0.001). A significant correlation was also observed between the size of the ischemic lesion (infarct plus penumbra) on the admission perfusion CT and the abnormality size on the mean transit time map calculated from admission PWI (
r
=0.946,
P
<0.001). Information about cerebral infarct and total ischemia (infarct plus penumbra) carried by both imaging techniques was similar, with slopes of 0.913 and 0.905, respectively.

Conclusions

—

An imaging technique may be helpful in the identification of cerebral penumbra in acute stroke patients and thus in the selection of patients for thrombolytic therapy. Perfusion CT and DWI/PWI are equivalent in this task.
The Long Peace: A Reconsideration
Authors: Siverson Randolph M. , Ward Michael D.
Published: October 2002

In this article, we reconsider the rarity of the Long Peace in the light of a probability model that targets the collective experience of major powers. Our examination shows that consecutive periods of peace equal to the forty-two years of the so-called Long Peace are not uncommon over the past eighteen decades—these periods occurred slightly more than 30 percent of the time. The period between 1816 and 1913 actually contains less war involvement by major powers than the period of the putative Long Peace. Our analysis demonstrates that long periods of major power peace are not unusual; periods of major power war are more exceptional than normal. Thus we conclude that the Long Peace is not rare and that its role in evaluating theories of war is misleading.
Drawing with the Hand in Free Space: Creating 3D Shapes with Gesture in a Semi-Immersive Environment
Authors: Schkolne Steven
Published: October 2002

This article presents a new medium in which organic surfaces are drawn in 3D space with the hand. Special interface hardware includes a head-tracked stereoscopic display and sensors that track the body and handheld tools, allowing the artist to share the space of the artwork. Additional tools move and deform the shape. This method provides a fluid, unstructured access to three dimensions, ideal for quick, spontaneous ideation and investigation of complex structures.