bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural study of a series of synthetic goethites obtained in aqueous solutions containing cadmium(II) ions
Authors: Sileo E. E. , Solı´s P. S. , Paiva-Santos C. O.
Published: March 2003

The capacity of goethite for CdIIsubstitution has been explored in a series of synthetic samples prepared from FeIIIand CdIInitrate solutions aged 21 days in alkaline media. The total metal content ([Fe]+[Cd]) was 0.071 M in all preparations. The samples have been characterized by chemical and X-ray diffraction analysis; the morphology of the solids is described. The cell parameters for all samples were obtained by the Rietveld fits to the X-ray diffraction data. Refined structures show that for samples prepared at the final molar ratio μCd≤5.50 (expressed as μCd=100×[Cd]/[Cd]+[Fe]), a (Cd, Fe)-goethite is the only crystalline product. In these samples, the unit cell parameters increased as a function of Cd concentration, indicating Cd incorporation in the structural frame. At the preparative ratio, μCd=7.03, the incorporation of Cd in the goethite structure is drastically reduced and a probable Cd-substituted hematite is formed together with the Fe,Cd-goethite.
Synthesis and powder diffraction analysis of tri-rubidium penta-tantalum oxide, Rb3Ta5O14, with novel three-dimensionally nanostructured Rb-bearing channels
Authors: Oono A. , Yashima M. , du Boulay D. , Ishizawa N. , Saiki A. , Oishi S.
Published: March 2003

The powder pattern of Rb3Ta5O14 is reported here for the first time. Single crystals of Rb3Ta5O14 of 0.1–0.2 mm in size were grown using a RbCl flux at 1100 °C. The Rb3Ta5O14 powders were synthesized at 1200 °C by firing the Rb2CO3 and Ta2O5 raw materials with starting Rb/Ta ratios ranging from 0.450 to 0.800. The products with Rb/Ta ratios between 0.550 and 0.633 contained almost pure Rb3Ta5O14 with Rb/Ta ratio of 0.600, while those with Rb/Ta ratio larger than 0.677 also contained the α form of Rb4Ta6O17 with the Rb/Ta ratio of 0.677. Past studies of the synthesis and characterization of Rb4Ta6O17 should be carefully examined in the light of possible coexistence with Rb3Ta5O14, because the former structure has not been completely solved, and thus the powder pattern is inaccurate, while the presence of the latter had not been known until the present study.
On reproducibility of Rietveld analysis of reference Portland cement clinkers
Authors: Pritula O. , Smrcˇok Lˇ. , Baumgartner B.
Published: March 2003

Weight fractions of four dominant phases (C3S, C2S, C4AF and C3A) present in the NIST Reference Portland clinkers 8486, 8487 and 8488 were estimated by a series of Rietveld refinements. Calculated powder patterns were derived from the structural data for monoclinic C3S and C2S, orthorhombic C4AF and cubic C3A. X-ray diffraction data were collected in two laboratories with two diffractometers, a reflection and a transmission one. There were no significant differences between the results of the refinements based on the data sets collected on the machines with different experimental arrangements. Estimated phase compositions were compared to the reference values found by optical microscopy (MPC). Median agreement between refined and reference values within ±5% (absolute) was found only for 8488 clinker; for 8486 and C3A-rich 8487 it was within ±10% (absolute). In the majority of the refinements numerical instabilities were detected, leading to large correlations between FWHM and temperature parameters of some phases. The results obtained for C4AF were probably influenced by the presence of possible solid solutions with the structures close to that of C4AF. Weight fractions of low abundant C3A were estimated with the largest relative errors reaching in several cases ∼100%.
Efferent Vagal Fibre Stimulation Blunts Nuclear Factor-κB Activation and Protects Against Hypovolemic Hemorrhagic Shock
Authors: Guarini Salvatore , Altavilla Domenica , Cainazzo Maria-Michela , Giuliani Daniela , Bigiani Albertino , Marini Herbert , Squadrito Giovanni , Minutoli Letteria , Bertolini Alfio , Marini Rolando , Adamo Elena B. , Venuti Francesco S. , Squadrito Francesco
Published: March 2003

Background—

We investigated whether electrical stimulation (STIM) of efferent vagus nerves may suppress nuclear factor (NF)-κB activation and the inflammatory cascade in hemorrhagic (Hem) shock.

Methods and Results—

Rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Hem shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mm Hg. Application of constant voltage pulses to the caudal vagus ends (STIM; 5 V, 2 ms, 1 Hz for 12 minutes, 5 minutes after mean arterial pressure stabilization) increased survival time (VGX+Hem+Sham STIM=38±3 minutes; VGX+Hem+STIM >180 minutes), reverted the marked hypotension (VGX+Hem+Sham STIM=33±3 mm Hg; VGX+Hem+STIM=66±5 mm Hg), inhibited IκBα liver loss, and blunted the augmented NF-κB activity, decreased hepatic tumor necrosis factor (TNF)-α mRNA (VGX+Hem+Sham STIM=1.42±0.5 amount of TNF-α m-RNA; VGX+Hem+STIM=0.51±0.2 amount of TNF-α mRNA), and reduced plasma TNF-α (VGX+Hem+Sham STIM=190±24 pg/mL; VGX+Hem+STIM=87±15 pg/mL). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation.

Conclusions—

Our results show a parasympathetic inhibition of NF-κB by which the brain opposes NF-κB activation in the liver and modulates the inflammatory response during acute hypovolemic hemorrhagic shock.
Asymptomatic or “Silent” Atrial Fibrillation
Authors: Page Richard L. , Tilsch Thomas W. , Connolly Stuart J. , Schnell Daniel J. , Marcello Stephen R. , Wilkinson William E. , Pritchett Edward L.C.
Published: March 2003

Background—

Asymptomatic, or “silent” atrial fibrillation could increase the risk of stroke. Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation; similarly, little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation.

Methods and Results—

Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide (35 to 125 mg) once daily for 6 or 9 months in 4 similar double-blind trials. The end point was the first recurrence of a symptomatic ECG-documented supraventricular arrhythmia. Routine transtelephonic electrocardiograms, in the absence of symptoms, were recorded for 30 seconds every 2 weeks until patients completed follow-up or documented a symptomatic supraventricular arrhythmia. Of the 1380 patients, 489 received placebo. Among these patients receiving placebo, 303 transmitted at least one routine ECG while asymptomatic. Asymptomatic atrial fibrillation was recorded in 50 (17%) within 6 months and before recurrence of symptomatic supraventricular arrhythmia. In the 3 trials evaluating azimilide in therapeutic doses (100 and 125 mg), asymptomatic atrial fibrillation occurred in 49 of 382 (13%) receiving azimilide and 43 of 233 (18%) receiving placebo. Although drug effect on time to first asymptomatic event was not statistically significant (hazard ratio, 0.70;
P
=0.09), there was a 40% reduction in asymptomatic atrial fibrillation on azimilide compared with placebo (
P
=0.03) when repeated observations were considered.

Conclusions—

Asymptomatic atrial fibrillation is common in untreated patients with a history of symptomatic atrial fibrillation (and is likely underestimated by this analysis). Azimilide may reduce the occurrence of this silent arrhythmia.
Oral Health and Peripheral Arterial Disease
Authors: Hung Hsin-Chia , Willett Walter , Merchant Anwar , Rosner Bernard A. , Ascherio Alberto , Joshipura Kaumudi J.
Published: March 2003

Background—

Many studies have reported the association between poor oral health and coronary heart disease or stroke, but few of them evaluated peripheral arterial disease (PAD). Hence, in this study we examined the associations between oral health and PAD.

Methods and Results—

In the prospective study of 45 136 eligible male health professionals free of cardiovascular diseases at baseline, we identified 342 cases of PAD during a 12-year follow-up period. We evaluated the association between different measures of oral diseases and the occurrence of PAD. Baseline number of teeth was not related to the risk of PAD, but cumulative incident tooth loss was significantly associated with elevated risk of subsequent occurrence of PAD. The relative risk for history of periodontal disease was 1.41 (95% CI, 1.12 to 1.77) and for any tooth loss during the follow-up period was 1.39 (95% CI, 1.07 to 1.82), controlling for traditional risk factors of cardiovascular disease. Among men with a history of periodontal diseases, the relative risk of tooth loss increased to 1.88 (95% CI, 1.27 to 2.77), whereas no association was found between tooth loss and PAD among those without periodontal diseases (RR, 0.92; 95% CI, 0.61 to 1.38). We further explored the potential induction period of tooth loss and found that tooth loss in the previous 2 to 6 years was most strongly associated with PAD.

Conclusions—

We found that incident tooth loss was significantly associated with PAD, especially among men with periodontal diseases. The results support a potential oral infection–inflammation pathway.
MCC-134, a Single Pharmacophore, Opens Surface ATP–Sensitive Potassium Channels, Blocks Mitochondrial ATP–Sensitive Potassium Channels, and Suppresses Preconditioning
Authors: Sasaki Norihito , Murata Mitsushige , Guo Yiru , Jo Su-Hyun , Ohler Andreas , Akao Masaharu , O’Rourke Brian , Xiao Rui-Ping , Bolli Roberto , Marbán Eduardo
Published: March 2003

Background—

MCC-134 (1-[4-(
H
-imidazol-1-yl)benzoyl]-
N
-methylcyclobutane-carbothioamide), a newly developed analog of aprikalim, opens surface smooth muscle–type ATP-sensitive potassium (K
ATP
) channels but inhibits pancreatic K
ATP
channels. However, the effects of MCC-134 on cardiac surface K
ATP
channels and mitochondrial K
ATP
(mitoK
ATP
) channels are unknown. A mixed agonist/blocker with differential effects on the two channel types would help to clarify the role of K
ATP
channels in cardioprotection.

Methods and Results—

To index mitoK
ATP
channels, we measured mitochondrial flavoprotein fluorescence in rabbit ventricular myocytes. MCC-134 alone had little effect on basal flavoprotein fluorescence. However, MCC-134 inhibited diazoxide-induced flavoprotein oxidation in a dose-dependent manner (EC
50
=27 μmol/L). When ATP was included in the pipette solution, MCC-134 slowly activated surface K
ATP
currents with some delay (>10 minutes). These results indicate that MCC-134 is a mitoK
ATP
channel inhibitor and a surface K
ATP
channel opener in native cardiac cells. In cell-pelleting ischemia assays, coapplication of MCC-134 with diazoxide abolished the cardioprotective effect of diazoxide, whereas MCC-134 alone did not alter cell death. These results were reproducible in both rabbit and mouse myocytes. MCC-134 also attenuated the effect of ischemic preconditioning against myocardial infarction in mice, consistent with the results of cell-pelleting ischemia assays.

Conclusions—

A single drug, MCC-134, opens surface K
ATP
channels but blocks mitoK
ATP
channels; the fact that this drug inhibits preconditioning reaffirms the primacy of mitoK
ATP
rather than surface K
ATP
, channels in the mechanism of cardioprotection.
Carotid Arterial Structure in Patients With Documented Coronary Artery Disease and Disease-Free Control Subjects
Authors: Terry James G. , Tang Rong , Espeland Mark A. , Davis Donna H. , Vieira Jose L.C. , Mercuri Michele F. , Crouse John R.
Published: March 2003

Background—

Although atherosclerosis often leads to lumen narrowing and symptomatic cardiovascular disease, it is now recognized that arteries have the potential to compensate by enlarging in response to atherosclerosis. We tested the hypotheses that carotid arterial interadventitial (IA) and lumen diameters were related to wall thickness and that carotid arterial diameters of individuals with coronary artery disease (CAD) differed from those of CAD-free controls.

Methods and Results—

We measured lumen diameter, IA diameter, and intima-media thickness (IMT) using B-mode ultrasound in the common and internal carotid arteries of 141 CAD case patients and 139 disease-free control subjects. Common carotid IA diameter was greater in CAD cases than controls after adjustment for age, height, and sex (
P
<0.01). Common carotid lumen diameter was marginally larger in individuals with greater IMT (
P
=0.06) but was not associated with case status. Conversely, mean internal carotid IA and lumen diameters were smaller in CAD cases than controls in both univariable and multivariable models (both
P
<0.001), and lumina were smaller in individuals with greater IMT. Despite these cross-sectional differences in carotid artery dimensions, we were unable to detect any statistically significant interactive effects of CAD case status on the association of IMT with arterial dimensions.

Conclusions—

Internal carotid artery lumen and IA diameters are both smaller in CAD cases than controls. The association of increased IMT with arterial dimensions varies in a manner that is segment-specific for the common and internal carotid arteries.
Contractile Reserve and Calcium Regulation Are Depressed in Myocytes From Chronically Unloaded Hearts
Authors: Ito Kenta , Nakayama Masaharu , Hasan Faisal , Yan Xinhua , Schneider Michael D. , Lorell Beverly H.
Published: March 2003

Background—

Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known.

Methods and Results—

Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca
2+
]
i
regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca
2+
]
o
, and 36°C) and in response to stimulation with high [Ca
2+
]
o
(range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca
2+
]
i
at baseline; however, time to 50% relengthening and time to 50% decline in [Ca
2+
]
i
were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca
2+
]
i
were elicited in myocytes from 5-week unloaded hearts in response to high [Ca
2+
]
o
. However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca
2+
ATPase and the Na
+
/Ca
2+
exchanger were not changed.

Conclusions—

Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.
No Evidence of Association Between Prothrombotic Gene Polymorphisms and the Development of Acute Myocardial Infarction at a Young Age
Authors:   Atherosclerosis, Thrombosis, and Vascular Biology Italian Study Group
Published: March 2003

Background—

We investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state.

Methods and Results—

This nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of <45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A β-fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction.

Conclusions—

This study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it.
Metabolism of Asymmetric Dimethylarginines Is Regulated in the Lung Developmentally and With Pulmonary Hypertension Induced by Hypobaric Hypoxia
Authors: Arrigoni Francesca I. , Vallance Patrick , Haworth Sheila G. , Leiper James M.
Published: March 2003

Background—

Nitric oxide (NO) plays an important part in lowering pulmonary vascular resistance after birth, and in persistent pulmonary hypertension of the newborn (PPHN), NO-mediated dilation is dysfunctional. The endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) circulates in plasma, and its concentrations are elevated in certain cardiovascular diseases, including pulmonary hypertension. ADMA is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the activity of which regulates ADMA concentrations and provides a mechanism for modulating NO synthase in vivo. We investigated the changes in expression and activity of the 2 isoforms of DDAH in lungs from newborn piglets both during normal development and in PPHN.

Methods and Results—

Using Western blotting, we showed that DDAHI expression did not change in the normal developing lung; however, DDAHII increased after birth and reached a peak at 1 day. This was reflected in an increase in total DDAH activity according to an
l
-citrulline assay. With pulmonary hypertension, no changes in DDAHI expression were observed, but DDAHII expression was markedly decreased compared with age-matched controls. Total DDAH activity was similarly reduced.

Conclusions—

These results indicate that each DDAH isoform is differentially regulated during both lung development and PPHN. Suppression of DDAHII isoform expression may be a mechanism underlying PPHN.
Decreased Efficiency of Adenovirus-Mediated Gene Transfer in Aging Cardiomyocytes
Authors: Communal Catherine , Huq Fawzia , Lebeche Djamel , Mestel Celine , Gwathmey Judith K. , Hajjar Roger J.
Published: March 2003

Background—

Aging is an independent risk factor for the development of cardiovascular disease. Clinical application of myocardial gene transfer may be best suited in the elderly. In vivo gene transfer by adenovirus is less efficient in aging myocardium.

Methods and Results—

When infected with adenovirus containing β-galactosidase (β-gal) and green fluorescent protein (GFP) driven by cytomegalovirus promoters in vitro, aging rat cardiac myocytes exhibit significantly lower infectivity and delayed transgene expression compared with adult controls. Abnormalities of viral internalization may be one mechanism accounting for this difference. To investigate this, we studied expression levels of the coxsackievirus and adenovirus receptor (CAR) as well as other potential integrins involved in the internalization of adenoviruses. CAR expression tended to be upregulated whereas among potential integrins, α
3
β
1
was downregulated in aging cardiac myocytes. Blocking the β
1
component of α
3
β
1
further decreased infectivity, suggesting that the interaction between the penton base of the adenovirus and β
1
maybe a crucial component of the viral entry mechanism.

Conclusions—

These results suggest that it is integrin-stimulated internalization rather than the adenovirus-CAR interaction that plays a vital role in adenoviral entry. The downregulation of integrins observed in senescent cells may be a key mechanism accounting for the decrease in viral infectivity seen in these cells. These findings have implications for the gene therapy treatment of myocardial failure in the elderly.
Relative Intensity of Physical Activity and Risk of Coronary Heart Disease
Authors: Lee I-Min , Sesso Howard D. , Oguma Yuko , Paffenbarger Ralph S.
Published: March 2003

Background—

Current recommendations prescribe at least moderate-intensity physical activity, requiring ≥3 METs (metabolic equivalents) for ≥30 minutes almost daily, generating ≈1000 kcal/wk. Defining intensity using an absolute scale in METs may be limited because it neglects variations in physical fitness: an activity requiring a particular MET value commands greater physical effort among less fit than more fit persons. It is unknown whether moderate-intensity exercise, relative to an individual’s capacity, is associated with reduced coronary heart disease (CHD) rates.

Methods and Results—

We followed 7337 men (mean age, 66 years) from 1988 to 1995. At baseline, men reported their actual activities and, using the Borg Scale, the perceived level of exertion when exercising (relative intensity). During follow-up, 551 men developed CHD. After multivariate adjustment, the relative risks of CHD among men who perceived their exercise exertion as “moderate,” “somewhat strong,” and “strong” or more intense were 0.86 (95% confidence interval, 0.66 to 1.13), 0.69 (0.51 to 0.94), and 0.72 (0.52 to 1.00), respectively (
P
trend
=0.02), compared with “weak” or less intense. This inverse association extended to men not fulfilling current recommendations, ie, expending <1000 kcal/wk in physical activity or not engaging in activities of ≥3 METs (
P
trend
=0.03 and 0.007, respectively).

Conclusions—

There is an inverse association between relative intensity of physical activity (an individual’s perceived level of exertion) and risk of CHD, even among men not satisfying current activity recommendations. Recommendations for “moderate”-intensity physical activity may need to consider individual fitness levels instead of globally prescribing activities of ≥3 METs.
Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients With Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure
Authors: Yokoe Takuya , Minoguchi Kenji , Matsuo Hirofumi , Oda Naruhito , Minoguchi Hideko , Yoshino Gen , Hirano Tsutomu , Adachi Mitsuru
Published: March 2003

Background—

C-reactive protein (CRP) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease. In the present study, we examined serum levels of CRP and IL-6, IL-6 production by monocytes, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS).

Methods and Results—

After polysomnography, venous blood was collected at 5
am
from 30 patients with OSAS and 14 obese control subjects. Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated. In addition, the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS. Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects (CRP
P
<0.001, IL-6
P
<0.05). IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects (
P
<0.01). In patients with OSAS, the primary factors influencing levels of CRP were severity of OSAS and body mass index and those influencing levels of IL-6 were body mass index and nocturnal hypoxia. nCPAP significantly decreased levels of both CRP (
P
<0.0001) and IL-6 (
P
<0.001) and spontaneous IL-6 production by monocytes (
P
<0.01).

Conclusions—

Levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP. Therefore, OSAS is associated with increased risks for cardiovascular morbidity and mortality, and nCPAP may be useful for decreasing these risks.
Intramural Hematoma of the Aorta
Authors: von Kodolitsch Yskert , Csösz Susanne K. , Koschyk Dietmar H. , Schalwat Ilka , Loose Roger , Karck Matthias , Dieckmann Christoph , Fattori Rossella , Haverich Axel , Berger Jürgen , Meinertz Thomas , Nienaber Christoph A.
Published: March 2003

Background—

Aortic intramural hematoma (IMH) is a variant of overt aortic dissection. The predictors of progression of IMH to dissection and rupture are still unknown, and strategies for management are not established.

Methods and Results—

A multicenter study was conducted comprising 66 patients with IMH and hospital admission ≤48 hours after onset of initial symptoms. Among these, progression to aortic dissection or rupture occurred in 30 (45%) and death occurred in 13 (20%) patients within 30 days. Late progression was noted in 14 (21%) and death in 11 (17%) patients, yielding a 1-, 2-, and 5-year survival of 76%, 73%, and 43%, respectively. In a set of 9 variables, multivariate analysis identified IMH location in the ascending aorta (type A;
P
=0.02) and moderately ectatic aortic diameters (49±13 mm with progression versus 57±16 mm without progression;
P
=0.03) as independent predictors of early progression. In type A IMH, early mortality was 8% with swift surgery versus 55% without surgery (
P
=0.004). The risk of late progression of IMH was independently associated with age at index diagnosis (
P
=0.01) and absence of β-blocker therapy during follow-up (
P
=0.03). Kaplan-Meier analysis confirmed improved 1-year survival of IMH with β-blocker therapy (95% versus 67% without β-blockers;
P
=0.004).

Conclusions—

Regardless of aortic diameter, IMH of the ascending aorta (type A) is at high risk for early progression, and, thus, undelayed surgical repair should be performed. Moreover, oral β-blocker therapy may improve long-term prognosis of IMH independent of anatomical location.
Geometric Differences of the Mitral Apparatus Between Ischemic and Dilated Cardiomyopathy With Significant Mitral Regurgitation
Authors: Kwan Jun , Shiota Takahiro , Agler Deborah A. , Popović Zoran B. , Qin Jian Xin , Gillinov Marc A. , Stewart William J. , Cosgrove Delos M. , McCarthy Patrick M. , Thomas James D.
Published: March 2003

Background—

This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE).

Methods and Results—

Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aα; posterior, Pα) were measured. In ICM-MR, Aα measured in the medial and central planes was significantly larger than that in the lateral plane (39±5°, 34±6°, and 27±5°, respectively;
P
<0.01), whereas Pα showed no significant difference in any of the 3 AP planes (61±7°, 57±7°, and 56±7°,
P
>0.05). In DCM-MR, both Aα (38±8°, 37±9°, and 36±7°,
P
>0.05) and Pα (59±6°, 58±5°, and 57±6°,
P
>0.05) revealed no significant differences in the 3 planes.

Conclusions—

The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.
Inhibitory Effects of Glycoprotein IIb/IIIa Antagonists and Aspirin on the Release of Soluble CD40 Ligand During Platelet Stimulation
Authors: Nannizzi-Alaimo Lisa , Alves Veronica L. , Phillips David R.
Published: March 2003

Background—

Glycoprotein (GP) IIb/IIIa antagonists inhibit platelet aggregation, an activity attributed to the clinical benefits of these drugs in settings that involve acute coronary thrombosis. However, platelet activation and subsequent aggregation are now known to cause the release of a soluble form of CD40 ligand (sCD40L), a prothrombotic and proinflammatory protein with GP IIb/IIIa binding activity and an established role in atherosclerotic lesion progression. The present study was designed to determine what effect GP IIb/IIIa antagonists have on the release of sCD40L.

Methods and Results—

Doses of eptifibatide, abciximab, and tirofiban that inhibited platelet aggregation by at least 80% also inhibited sCD40L release in vitro (by 85%, 57%, and 80%, respectively). When platelets were stimulated with a thrombin receptor agonist, inhibition by GP IIb/IIIa antagonists occurred without affecting the release of βTG, an α-granule protein. Unexpectedly, concentrations of the 3 antagonists that blocked aggregation by only 20% to 50% potentiated the release of sCD40L (by 19% to 26%). Platelets from aspirin-treated individuals were partially protected from sCD40L release, but only when the agonist was collagen, an affect augmented by the addition of GP IIb/IIIa antagonists.

Conclusions—

These studies suggest that the mechanisms responsible for the clinical benefits of GP IIb/IIIa antagonists (at doses that optimally inhibit aggregation) and of aspirin may not be limited to the inhibition of thrombosis through their blockade of platelet aggregation but may also involve the inhibition of inflammation and thrombosis through their blockade of sCD40L release. These studies also provide a mechanism by which suboptimal doses of GP IIb/IIIa antagonists may be proinflammatory.
Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis
Authors: Nemmar Abderrahim , Hoet Peter H.M. , Dinsdale David , Vermylen Jozef , Hoylaerts Marc F. , Nemery Benoit
Published: March 2003

Background—

Pollution by particulates has consistently been associated with increased cardiovascular morbidity and mortality, but a plausible biological basis for this association is lacking.

Methods and Results—

Diesel exhaust particles (DEPs) were instilled into the trachea of hamsters, and blood platelet activation, experimental thrombosis, and lung inflammation were studied. Doses of 5 to 500 μg of DEPs per animal induced neutrophil influx into the bronchoalveolar lavage fluid with elevation of protein and histamine but without lactate dehydrogenase release. The same doses enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 minutes after instillation of 50 μg of DEPs yielded accelerated aperture closure (ie, platelet activation) ex vivo, when analyzed in the Platelet Function Analyser (PFA-100). The direct addition of as little as 0.5 μg/mL DEPs to untreated hamster blood significantly shortened closure time in vitro.

Conclusions—

The intratracheal instillation of DEPs leads to lung inflammation as well as a rapid activation of circulating blood platelets. The kinetics of platelet activation are consistent with the reported clinical occurrence of thrombotic complications after exposure to pollutants. Our findings, therefore, provide a plausible explanation for the increase in cardiovascular morbidity and mortality accompanying urban air pollution.
Peripheral Blood “Endothelial Progenitor Cells” Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors
Authors: Rehman Jalees , Li Jingling , Orschell Christie M. , March Keith L.
Published: March 2003

Background—

Endothelial progenitor cells (EPCs) have been isolated from peripheral blood and can enhance angiogenesis after infusion into host animals. It is not known whether the proangiogenic effects are a result of such events as endothelial differentiation and subsequent proliferation of EPCs or secondary to secretion of angiogenic growth factors.

Methods and Results—

Human EPCs were isolated as previously described, and their phenotypes were confirmed by uptake of acetylated LDL and binding of ulex-lectin. EPC proliferation and surface marker expression were analyzed by flow cytometry, and conditioned medium was assayed for growth factors. The majority of EPCs expressed monocyte/macrophage markers such as CD14 (95.7±0.3%), Mac-1 (57.6±13.5%), and CD11c (90.8±4.9%). A much lower percentage of cells expressed the specific endothelial marker VE-cadherin (5.2±0.7%) or stem/progenitor-cell markers AC133 (0.16±0.05%) and c-kit (1.3±0.7%). Compared with circulating monocytes, cultured EPCs showed upregulation of monocyte activation and macrophage differentiation markers. EPCs did not demonstrate any significant proliferation but did secrete the angiogenic growth factors vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony–stimulating factor, and granulocyte-macrophage colony–stimulating factor.

Conclusions—

Our findings suggest that acetylated LDL(+)ulex-lectin(+) cells, commonly referred to as EPCs, do not proliferate but release potent proangiogenic growth factors. The majority of acetylated LDL(+)ulex-lectin(+) cells are derived from monocyte/macrophages. The findings of low proliferation and endothelial differentiation suggest that their angiogenic effects are most likely mediated by growth factor secretion. These findings may allow for development of novel angiogenic therapies relying on secreted growth factors or on recruitment of endogenous monocytes/macrophages to sites of ischemia.
Serum C-Reactive Protein Level Is Associated With Abdominal Aortic Aneurysm Size and May Be Produced by Aneurysmal Tissue
Authors: Vainas Tryfon , Lubbers Tim , Stassen Frank R.M. , Herngreen Selma B. , van Dieijen-Visser Marja P. , Bruggeman Cathrien A. , Kitslaar Peter J.E.H.M. , Schurink Geert Willem H.
Published: March 2003

Background—

Abdominal aortic aneurysms (AAA) are characterized by extensive transmural inflammation and C-reactive protein (CRP) has emerged as an independent risk factor for the development of cardiovascular disease. Therefore, we evaluated a possible association between serum CRP and aneurysm dimension in patients with asymptomatic AAA. Furthermore, the possibility of CRP production by aneurysmal tissue has been examined.

Methods and Results—

Serum CRP was determined highly sensitive (
hs
CRP) and aneurysmal size was measured in 39 patients with AAA. The presence of CRP mRNA was assessed in the aneurysmal tissue of 16 patients. Mean (SD)
hs
CRP was 3.23 (2.96) mg/L. After log-transformation,
hs
CRP correlated significantly with aneurysmal size (
r
=0.477,
P
=0.002). When the patients were divided into 3 equally sized groups according to
hs
CRP level, aortic diameter increased from lowest to upper
hs
CRP-tertile (49 mm, 61 mm, and 67 mm, respectively;
P
<0.05 for 3rd versus 1st tertile). This association persisted after correction for risk factors. CRP mRNA was found in 25% of aneurysmal aortic tissues.

Conclusions—

This is the first report showing that serum
hs
CRP is associated with aneurysmal size and that—in at least some patients—CRP may be produced by aneurysmal tissue. These data underscore the inflammatory nature of AAA formation, suggesting that serum
hs
CRP may serve as a marker of AAA disease and that CRP produced in vascular tissue might contribute to aneurysm formation.
Expression and Function of a Biological Pacemaker in Canine Heart
Authors: Qu Jihong , Plotnikov Alexei N. , Danilo Peter , Shlapakova Iryna , Cohen Ira S. , Robinson Richard B. , Rosen Michael R.
Published: March 2003

Background—

We hypothesized that localized overexpression of the hyperpolarization-activated, cyclic nucleotide-gated (HCN2) pacemaker current isoform in canine left atrium (LA) would constitute a novel biological pacemaker.

Methods and Results—

Adenoviral constructs of mouse HCN2 and green fluorescent protein (GFP) or GFP alone were injected into LA, terminal studies performed 3 to 4 days later, hearts removed, and myocytes examined for native and expressed pacemaker current (
I
f
). Spontaneous LA rhythms occurred after vagal stimulation-induced sinus arrest in 4 of 4 HCN2+GFP dogs and 0 of 3 GFP dogs (
P
<0.05). Native
I
f
in nonexpressed atrial myocytes was 7±4 pA at −130 mV (n=5), whereas HCN2+GFP LA had expressed pacemaker current (
I
HCN2
) of 3823±713 pA at −125 mV (n=10) and 768±365 pA at −85 mV.

Conclusions—

HCN2 overexpression provides an
I
f
-based pacemaker sufficient to drive the heart when injected into a localized region of atrium, offering a promising gene therapy for pacemaker disease.
Form-From-Motion: MEG Evidence for Time Course and Processing Sequence
Authors: Schoenfeld M. A. , Woldorff M. , Düzel E. , Scheich H. , Heinze H.-J. , Mangun G. R.
Published: March 2003

The neural mechanisms and role of attention in the processing of visual form defined by luminance or motion cues were studied using magnetoencephalography. Subjects viewed bilateral stimuli composed of moving random dots and were instructed to covertly attend to either left or right hemifield stimuli in order to detect designated target stimuli that required a response. To generate form-from-motion (FFMo) stimuli, a subset of the dots could begin to move coherently to create the appearance of a simple form (e.g., square). In other blocks, to generate form-from-luminance (FFLu) stimuli that served as a control, a gray stimulus was presented superimposed on the randomly moving dots. Neuromagnetic responses were observed to both the FFLu and FFMo stimuli and localized to multiple visual cortical stages of analysis. Early activity in low-level visual cortical areas (striate/early extrastriate) did not differ for FFLu versus FFMo stimuli, nor as a function of spatial attention. Longer latency responses elicited by the FFLu stimuli were localized to the ventral-lateral occipital cortex (LO) and the inferior temporal cortex (IT). The FFMo stimuli also generated activity in the LO and IT, but only after first eliciting activity in the lateral occipital cortical region corresponding to MT/V5, resulting in a 50–60 msec delay in activity. All of these late responses (MT/V5, LO, and IT) were significantly modulated by spatial attention, being greatly attenuated for ignored FFLu and FFMo stimuli. These findings argue that processing of form in IT that is defined by motion requires a serial processing of information, first in the motion analysis pathway from V1 to MT/V5 and thereafter via the form analysis stream in the ventral visual pathway to IT.
Motion Perception in Autism: A “Complex” Issue
Authors: Bertone Armando , Mottron Laurent , Jelenic Patricia , Faubert Jocelyn
Published: March 2003

We present the first assessment of motion sensitivity for persons with autism and normal intelligence using motion patterns that require neural processing mechanisms of varying complexity. Compared to matched controls, our results demonstrate that the motion sensitivity of observers with autism is similar to that of nonautistic observers for different types of first-order (luminance-defined) motion stimuli, but significantly decreased for the same types of second-order (texture-defined) stimuli. The latter class of motion stimuli has been demonstrated to require additional neural computation to be processed adequately. This finding may reflect less efficient integrative functioning of the neural mechanisms that mediate visuoperceptual processing in autism. The contribution of this finding with regards to abnormal perceptual integration in autism, its effect on cognitive operations, and possible behavioral implications are discussed.
Category-Specific Representations of Social and Nonsocial Knowledge in the Human Prefrontal Cortex
Authors: Wood J. N. , Romero S. G. , Makale M. , Grafman J.
Published: March 2003

Complex social behavior and the relatively large size of the prefrontal cortex are arguably two of the characteristics that distinguish humans from other animals. Grafman presented a framework concerning how the prefrontal cortex (PFC) controls complex behavior using stored structured event complexes (SECs). We report behavioral and imaging data from a modified go/no-go paradigm in which subjects had to classify words (semantic) and phrases (SEC) according to category. In experimental trials, subjects classified items according to social or nonsocial activity; in control trials, they classified items according to font. Subjects were faster to classify social than nonsocial semantic items, with the reverse pattern evident for the social and nonsocial SEC items. In addition, the conditions were associated with different patterns of PFC activation. These results suggest that there are different psychological and neural substrates for social and nonsocial semantic and SEC representations.
Neuroimaging Studies of Word and Pseudoword Reading: Consistencies, Inconsistencies, and Limitations
Authors: Mechelli Andrea , Gorno-Tempini Maria Luisa , Price Cathy J.
Published: March 2003

Several functional neuroimaging studies have compared words and pseudowords to test different cognitive models of reading. There are difficulties with this approach, however, because cognitive models do not make clear-cut predictions at the neural level. Therefore, results can only be interpreted on the basis of prior knowledge of cognitive anatomy. Furthermore, studies comparing words and pseudowords have produced inconsistent results. The inconsistencies could reflect false-positive results due to the low statistical thresholds applied or confounds from nonlexical aspects of the stimuli. Alternatively, they may reflect true effects that are inconsistent across subjects; dependent on experimental parameters such as stimulus rate or duration; or not replicated across studies because of insufficient statistical power.

In this fMRI study, we investigate consistent and inconsistent differences between word and pseudoword reading in 20 subjects, and distinguish between effects associated with increases and decreases in activity relative to fixation. In addition, the interaction of word type with stimulus duration is explored. We find that words and pseudowords activate the same set of regions relative to fixation, and within this system, there is greater activation for pseudowords than words in the left frontal operculum, left posterior inferior temporal gyrus, and the right cerebellum. The only effects of words relative to pseudowords consistent over subjects are due to decreases in activity for pseudowords relative to fixation; and there are no significant interactions between word type and stimulus duration. Finally, we observe inconsistent but highly significant effects of word type at the individual subject level.

These results (i) illustrate that pseudowords place increased demands on areas that have previously been linked to lexical retrieval, and (ii) highlight the importance of including one or more baselines to qualify word type effects. Furthermore, (iii) they suggest that inconsistencies observed in the previous literature may result from effects arising from a small number of subjects only.
Frontal and Parietal Components of a Cerebral Network Mediating Voluntary Attention to Novel Events
Authors: Daffner K. R. , Scinto L. F. M. , Weitzman A. M. , Faust R. , Rentz D. M. , Budson A. E. , Holcomb P. J.
Published: March 2003

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.
Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells
Authors: Perez-Cruz Isabel , Carcamo Juan M. , Golde David W.
Published: March 2003

The FAS receptor—FAS ligand system is a key apoptotic pathway for cells of the immune system. Ligation of the FAS-receptor (CD95) induces apoptosis by activation of pro—caspase-8 followed by downstream events, including an increase in reactive oxygen species (ROS) and the release of proapoptotic factors from the mitochondria, leading to caspase-3 activation. We investigated the role of vitamin C in FAS-mediated apoptosis and found that intracellular accumulation of pharmacologic concentrations of vitamin C inhibited FAS-induced apoptosis in the monocytic U937 cell line and in fresh human monocytes. Cells were loaded with vitamin C by exposure to dehydroascorbic acid (DHA), thereby circumventing in vitro artifacts associated with the poor transport and pro-oxidant effects of ascorbic acid (AA). Vitamin C inhibition of FAS-mediated apoptosis was associated with reduced activity of caspase-3, -8, and -10, as well as diminished levels of ROS and preservation of mitochondrial membrane integrity. Mechanistic studies indicated that the major effect of vitamin C was inhibition of the activation of caspase-8 with no effect on it enzymatic activity. An independent action of high intracellular concentrations of vitamin C on mitochondrial membrane stabilization was also detected. These studies illuminate the nature of redox-dependent signaling in FAS-induced apoptosis of human monocytes and suggest that vitamin C can modulate the immune system by inhibiting FAS-induced monocyte death. (Blood. 2003;102:336-343)