bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendritic Cells Are Present in Ischemic Brain After Permanent Middle Cerebral Artery Occlusion in the Rat
Authors: Kostulas Nikolaos , Li Hu-Lun , Xiao Bao-Guo , Huang Yu-Min , Kostulas Vasilios , Link Hans
Published: July 2002

Background and Purpose

—

Cerebral ischemia is associated with inflammation involving accumulation of polymorphonuclear neutrophils. T cells have been suggested to contribute to the secondary progression of ischemic brain injury. Dendritic cells (DC) are potent regulators of immunity by activating and tolerizing T cells. DC have previously been detected in rat meninges and choroid plexus. Hypothesizing that DC are involved in inflammation associated with cerebral ischemia, we investigated DC in the brain of Sprague-Dawley rats after permanent middle cerebral artery occlusion (pMCAO) versus sham operation.

Methods

—

All experimental rats (n=24) had the right MCA permanently occluded by inserting a nylon monofilament through the right external carotid artery. Immunohistochemistry was used to detect DC (OX62
+
), microglia/macrophages (OX42
+
) that developed into DC, and activated DC expressing major histocompatibility complex class II (OX6
+
) in the brain hemispheres at 1 hour to 6 days after pMCAO or sham operation.

Results

—

Levels of DC were elevated at 1 hour in the ischemic versus sham hemispheres (
P
<0.001) and ischemic versus nonischemic hemispheres (
P
<0.001). Activated DC expressing major histocompatibility complex class II (OX62
+
OX6
+
) were still elevated at 6 days after pMCAO in the ischemic versus nonischemic hemispheres (
P
<0.01). The area of brain lesion correlated with numbers of OX62
+
DC per 100-mm
2
brain tissue section (
r
=0.79;
P
<0.0001).

Conclusions

—

Increased levels of DC in the brain after pMCAO and correlation between DC numbers and brain lesion area indicate a role for DC in cerebral ischemia. This observation could constitute a basis for further studies on the role of DC in inflammation related to cerebral ischemia.
CT Angiography With Whole Brain Perfused Blood Volume Imaging
Authors: Ezzeddine Mustapha A. , Lev Michael H. , McDonald Colin T. , Rordorf Guy , Oliveira-Filho Jamary , Aksoy Fatma Gul , Farkas Jeffrey , Segal Alan Z. , Schwamm Lee H. , Gonzalez R. Gilberto , Koroshetz Walter J.
Published: July 2002

Background and Purpose

—

In CT angiographic and perfusion imaging (CTA/CTP), rapid CT scanning is performed during the brief steady state administration of a contrast bolus, creating both vascular phase images of the major intracranial vessels and perfused blood volume-weighted parenchymal phase images of the entire brain. We assessed the added clinical value of the data provided by CTA/CTP over that of clinical examination and noncontrast CT (NCCT) alone.

Methods

—

NCCT and CTA/CTP imaging was performed in 40 patients presenting with an acute stroke. Short clinical vignettes were retrospectively prepared. After concurrent review of the vignettes and NCCT, a stroke neurologist rated infarct location, vascular territory, vessel(s) occluded, and Trial of Org 10172 in Acute Stroke Treatment (TOAST) and Oxfordshire Community Stroke Project classifications. The ratings were repeated after serial review of each of the CTA/CTP components: (1) axial CTA source images; (2) CTP whole brain blood volume-weighted source images; and (3) maximum-intensity projection 3-dimensional reformatted images. The sequential ratings for each case were compared with the final discharge assessment.

Results

—

Compared with the initial review after NCCT, CTA/CTP improved the overall accuracy of infarct localization (
P
<0.001), vascular territory determination (
P
=0.003), vessel occlusion identification (
P
<0.001), TOAST classification (
P
=0.039), and Oxfordshire Community Stroke Project classification (
P
<0.001) by 40%, 28%, 38%, 18%, and 32%, respectively.

Conclusions

—

Admission CTA/CTP imaging significantly improves accuracy, over that of initial clinical assessment and NCCT imaging alone, in the determination of infarct localization, site of vascular occlusion, and Oxfordshire classification in acute stroke patients.
Neonatal Cerebral Infarction Diagnosed by Diffusion-Weighted MRI
Authors: Mader Irina , Schöning Martin , Klose Uwe , Küker Wilhelm
Published: July 2002

Background

—

Seizures in the neonatal period may be the single symptom of acute ischemic cerebral infarction. It may be difficult to establish the diagnosis in the acute phase by the use of ultrasound, CT, and conventional MRI because of the high water content of the immature brain. Diffusion-weighted (DW) MRI is a very sensitive and fast imaging modality to visualize acute ischemic stroke in infants even before conventional MR images become abnormal. Signal abnormality in DW MRI, however, seems to follow a different time course than in older patients.

Case Description

—

DW MRI became falsely negative 1 week after stroke (pseudonormalization) in 2 newborn patients during persistence of signal abnormalities on turbo spin-echo images, whereas the so-called pseudonormalization in adults normally occurs within 10 to 14 days.

Conclusions

—

T2-weighted sequences should supplement DW images to reliably detect subacute ischemic infarctions in the neonatal period.
Stimulation of Cardiac Apoptosis in Essential Hypertension
Authors: González Arantxa , López Begoña , Ravassa Susana , Querejeta Ramón , Larman Mariano , Díez Javier , Fortuño María A.
Published: July 2002

We investigated whether cardiac apoptosis is stimulated in the heart of hypertensive patients and whether angiotensin II plays a role in such alteration. The study was performed in 28 patients with essential hypertension and no evidence of either ischemic cardiomyopathy or heart failure. After randomization, 14 patients were assigned to losartan and 14 patients to amlodipine treatment. At baseline and after 12 months, right septal endomyocardial biopsies were performed, and the number of apoptotic nuclei was assessed by DNA end-labeling (TUNEL). In addition, immunostaining for the active form of caspase-3 was also performed to assess apoptosis. Compared with normotensive autopsied hearts, both cardiomyocyte and noncardiomyocyte apoptosis were increased (
P
<0.001) in hypertensive hearts. Time-course changes in blood pressure during treatment were similar in the 2 groups of patients. In losartan-treated patients, both cardiomyocyte and noncardiomyocyte apoptosis decreased (
P
<0.05). Neither cardiomyocyte nor noncardiomyocyte apoptosis changed significantly in amlodipine-treated patients. These findings indicate that apoptosis is abnormally stimulated in the heart of patients with essential hypertension. Our data also suggest that the ability of antihypertensive treatment to inhibit cardiac apoptosis is independent of its antihypertensive efficacy. We propose that angiotensin II may participate in the stimulation of cardiac apoptosis in essential hypertension.
Cardiovascular Effects of Overexpression of Endothelial Nitric Oxide Synthase in the Rostral Ventrolateral Medulla in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Kishi Takuya , Hirooka Yoshitaka , Ito Koji , Sakai Koji , Shimokawa Hiroaki , Takeshita Akira
Published: July 2002

We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in γ-amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or β-galactosidase (Adβgal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.
CB
1
Receptor Antagonist SR141716A Inhibits Ca
2+
-Induced Relaxation in CB
1
Receptor-Deficient Mice
Authors: Bukoski Richard D. , Bátkai Sándor , Járai Zoltán , Wang Yanlin , Offertaler Laszlo , Jackson William F. , Kunos George
Published: July 2002

Mesenteric branch arteries isolated from cannabinoid type 1 receptor knockout (CB
1
−/−
) mice, their wild-type littermates (CB
1
+/+
mice), and C57BL/J wild-type mice were studied to test the hypothesis that murine arteries undergo high sensitivity Ca
2+
-induced relaxation that is CB
1
receptor dependent. Confocal microscope analysis of mesenteric branch arteries from wild-type mice showed the presence of Ca
2+
receptor-positive periadventitial nerves. Arterial segments of C57 control mice mounted on wire myographs contracted in response to 5 μmol/L norepinephrine and responded to the cumulative addition of extracellular Ca
2+
with a concentration-dependent relaxation that reached a maximum of 72.0±6.3% of the prerelaxation tone and had an EC
50
for Ca
2+
of 2.90±0.54 mmol/L. The relaxation was antagonized by precontraction in buffer containing 100 mmol/L K
+
and by pretreatment with 10 mmol/L tetraethylammonium. Arteries from CB
1
−/−
and CB
1
+/+
mice also relaxed in response to extracellular Ca
2+
with no differences being detected between the knockout and their littermate controls. SR141716A, a selective CB
1
antagonist, caused concentration-dependent inhibition of Ca
2+
-induced relaxation in both the knockout and wild-type strains (60% inhibition at 1 μmol/L). O-1918, a cannabidiol analog, had a similar blocking effect in arteries of both wild-type and CB
1
−/−
mice at 10 μmol/L. In contrast, 1 μmol/L SR144538, a cannabinoid type 2 receptor antagonist, or 50 μmol/L 18α-glycyrrhetinic acid, a gap junction blocker, were without effect. SR141716A (1 to 30 μmol/L) was also assessed for nonspecific actions on whole-cell K
+
currents in isolated vascular smooth muscle cells. SR141716A inhibited macroscopic K
+
currents at concentrations higher than those required to inhibit Ca
2+
-induced relaxation, and appeared to have little effect on currents through large conductance Ca
2+
-activated K
+
channels. These data indicate that arteries of the mouse relax in response to cumulative addition of extracellular Ca
2+
in a hyperpolarization-dependent manner and rule out a role for CB
1
or CB
2
receptors in this effect. The possible role of a nonclassical cannabinoid receptor is discussed.
Downregulation of Neuronal Nitric Oxide Synthase and Interleukin-1β Mediates Angiotensin II-Dependent Stimulation of Sympathetic Nerve Activity
Authors: Campese Vito M. , Ye Shaohua , Zhong Huiquin
Published: July 2002

Abstract—

There is substantial evidence that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity. We recently observed that nitric oxide and interleukin-1β (IL-1β) exert a tonic inhibitory action on central SNS activity. Moreover, in 2 rat models of neurogenic hypertension, one caused by intrarenal injection of phenol and the other by 5/6 nephrectomy, we observed that losartan, an Ang II type 1 receptor blocker, inhibits SNS activity and increases the abundance of IL-1β and the neuronal isoform of nitric oxide synthase (nNOS) in the posterior hypothalamic nuclei (PH), paraventricular nuclei (PVN), and locus ceruleus (LC). This raises the possibility that the stimulatory effects of Ang II on central SNS activity may be mediated by inhibition of nNOS and IL-1β. To test this hypothesis, we studied the effect of an intracerebroventricular (ICV) infusion of Ang II on blood pressure (BP), norepinephrine (NE) secretion from the PH, renal SNS activity (RSNA), and abundance of IL-1β and nNOS mRNA in the PH, PVN, and LC of normal Sprague-Dawley rats. Finally, we measured the concentration of nitrite/nitrate in the dialysate collected from the PH after Ang II or vehicle. ICV infusion of Ang II (100 ng/kg body wt dissolved in 10 μL of artificial cerebrospinal fluid) raised BP, RSNA, and NE secretion from the PH compared with control rats. Ang II reduced the abundance of IL-1β and nNOS mRNA in the PH, PVN, and LC. Pretreatment with losartan (10 μg/kg body wt dissolved in 10 μL of aCSF) given ICV 20 minutes before Ang II abolished the effects of Ang II on BP, RSNA, and NE secretion from the PH and IL-1β and nNOS mRNA. Ang II also decreased the secretion of NO from the PH. In conclusion, these studies suggest that Ang II inhibits the expression of IL-1β and nNOS in the brain. Because locally produced NO exerts a tonic inhibitory action on SNS activity, the decrease in NO expression caused by Ang II results in greater SNS activity.
Chronotropic Action of Angiotensin II in Neurons via Protein Kinase C and CaMKII
Authors: Sun Chengwen , Sumners Colin , Raizada Mohan K.
Published: July 2002

Angiotensin II (Ang II) plays an important role in the central control of blood pressure and baroreflexes. These effects are initiated by stimulation of Ang II type 1 (AT
1
) receptors on neurons within the hypothalamus and brain stem, and involve increasing the activity of noradrenergic, substance P, and glutamatergic pathways. The goal of this study is to investigate the intracellular signaling molecules, which are involved in mediating the Ang II-induced increases in neuronal activity. Using neurons in primary culture from newborn rat hypothalamus and brain stem, we have previously determined that Ang II elicits an AT
1
receptor-mediated inhibition of delayed rectifier K
+
current, a stimulation of Ca
2+
current, and a consequent increase in firing rate. In the present study we have demonstrated that this chronotropic action of Ang II in neuronal cultures involves activation of Ca
2+
-dependent signaling molecules. The Ang II-induced increase in firing rate was abolished by inhibition of phospholipase C with U73122 (10 μmol/L), and was attenuated by the protein kinase C inhibitor calphostin C (10 μmol/L) or by the calcium/calmodulin-dependent kinase II (CaMKII) inhibitor KN-93 (10 μmol/L). A combination of calphostin C and KN-93 completely inhibited this Ang II action. These results indicate that the AT
1
receptor-mediated increase in neuronal firing rate involves activation of both PKC and CaMKII, and suggest that these enzymes are potential targets for manipulating the central actions of Ang II.
Blood Pressure and NaCl-Sensitive Hypertension Are Influenced by Angiotensin-Converting Enzyme Gene Expression in Transgenic Mice
Authors: Carlson Scott H. , Oparil Suzanne , Chen Yiu-Fai , Wyss J. Michael
Published: July 2002

ACE plays an important role in the regulation of arterial pressure; however, a linear relationship between ACE expression and arterial pressure has not been demonstrated. The present study employed telemetric monitoring in female transgenic mice to determine the influence of partial and complete deletion of the ACE gene on basal arterial pressure and arterial pressure responses to a high-NaCl diet. On the basal NaCl diet, 24-hour mean arterial pressure was significantly correlated with the number of functional copies of the ACE gene; ie, arterial pressure was lowest in 0-copy (80±1 mm Hg), intermediate in 1-copy (100±1 mm Hg), and highest in 2-copy (113±1 mm Hg) ACE mice. The high-NaCl diet significantly increased mean arterial pressure in 0-copy (99±1 mm Hg) and 1-copy (108±1 mm Hg) mice but not in 2-copy mice (114±1 mm Hg). These results demonstrate a copy-dependent relationship between ACE gene expression and both basal arterial pressure and arterial pressure responses to a high-NaCl diet, suggesting that either partial or complete reduction in the ACE gene can alter arterial pressure.
Association Between Pulse Pressure and C-Reactive Protein Among Apparently Healthy US Adults
Authors: Abramson Jerome L. , Weintraub William S. , Vaccarino Viola
Published: July 2002

Elevated pulse pressure has been associated with an increased risk of cardiovascular disease, which is increasingly being seen as an inflammatory disease. Thus, the mechanism underlying the link between elevated pulse pressure and cardiovascular disease risk may be inflammation. However, investigators have not examined the relationship between pulse pressure and C-reactive protein, an inflammation marker that has been closely linked to cardiovascular risk. We examined the cross-sectional relationship between pulse pressure and C-reactive protein among 9867 healthy persons 17 years of age or older who participated in the Third National Health and Nutrition Examination Survey. The association between pulse pressure and the odds of having an elevated C-reactive protein level (≥0.66 mg/dL) was assessed by logistic regression. In a model that adjusted for systolic blood pressure, demographic factors, cholesterol, measures of obesity, smoking, alcohol consumption, physical activity, and antihypertensive medication use, a 10 mm Hg increase in pulse pressure was associated with a 15% increase in the odds of having an elevated C-reactive protein level (odds ratio, 1.15; 95% confidence interval, 1.01 to 1.31;
P
=0.04). When the same model was re-run adjusting for diastolic blood pressure instead of systolic blood pressure, a 10 mm Hg rise in pulse pressure was associated with a significant 12% increase in the odds of having an elevated C-reactive protein level. Systolic and diastolic blood pressure were unrelated to C-reactive protein once pulse pressure had been accounted for. Our results suggest that increases in pulse pressure are associated with elevated C-reactive protein levels among apparently healthy US adults, independent of systolic and diastolic blood pressure.
Renal Hemodynamic Control by Endothelin and Nitric Oxide Under Angiotensin II Blockade in Man
Authors: Montanari Alberto , Carra Nicoletta , Perinotto Patrizia , Iori Veronica , Fasoli Elena , Biggi Almerina , Novarini Almerico
Published: July 2002

To investigate whether endothelin-A receptors and nitric oxide modulate renal hemodynamics in man under angiotensin II receptor-1 blockade, 6 healthy volunteers, on a 240 mmol Na diet, underwent 4 separate renal hemodynamic measurements, in 3 of which endothelin-A blocker BQ-123 0.2 nmol · kg · min
−1
was infused for 90 minutes after pretreatment with either placebo, telmisartan 1 mg · kg · day
−1
for 3 days, or telmisartan as well, but with co-infusion of both BQ-123 and N
G
-nitro-
l
-arginine methylester 0.5 μg · kg · min
−1
. A fourth infusion was made with N
G
-nitro-
l
-arginine methylester alone. No change followed infusion of either N
G
-nitro-
l
-arginine methylester alone or BQ-123 alone. With BQ-123 after telmisartan, renal blood flow rose from 916±56 mL · min
−1
· 1.73 m
2
to 1047±51.2 (
P
<0.001), and renal vascular resistances fell from 89±7 mm Hg · min · L
−1
to 74±4 (
P
<0.001). These changes were fully abolished by the co-infused N
G
-nitro-
l
-arginine methylester. Infusion of BQ-123, devoid of renal hemodynamic effects at baseline, produces significant renal vasodilation when angiotensin II receptors are blocked, indicating an increasing renal hemodynamic role of endothelin-A–receptor activity. Because such a vasodilation is prevented by nonvasoconstricting microdoses of N
G
-nitro-
l
-arginine methylester, nitric oxide–endothelin balance controls substantially renal hemodynamics under angiotensin II blockade. These findings are consistent with a rationale of the association of endothelin-A blockers with angiotensin II blockers or angiotensin-converting enzyme inhibitors in treating nitric oxide–deficient conditions such as arterial hypertension, heart failure, and chronic renal diseases.
Targeted Proteomic Profiling of Renal Na
+
Transporter and Channel Abundances in Angiotensin II Type 1a Receptor Knockout Mice
Authors: Brooks Heddwen L. , Allred Alicia J. , Beutler Kathleen T. , Coffman Thomas M. , Knepper Mark A.
Published: July 2002

The renal tubule transporters responsible for Na
+
and water transport along the nephron have been identified and cloned, permitting comprehensive analysis of transporter protein abundance changes in complex physiological models by using a “targeted proteomics” approach. Here, we apply this approach to screen renal homogenates from mice in which the gene for the angiotensin II type 1a (AT
1a
) receptor has been deleted (versus wild-type mice) to determine which sodium transporters and channels are regulated by the AT
1a
receptor at the protein abundance level. In mice maintained on a low NaCl diet (<0.02% NaCl), (1) the abundances of 2 aldosterone-regulated transporters were markedly decreased in knockout versus wild-type mice, namely, the thiazide-sensitive cotransporter and the α-subunit of the amiloride-sensitive Na
+
channel (α-ENaC); (2) the abundances of β-ENaC and γ-ENaC were markedly increased; and (3) there were no significant changes in the abundances of the proximal tubule Na+-H
+
exchanger or the Na
+
-K
+
-2Cl
−
cotransporter of the thick ascending limb. When the experiment was repeated on higher NaCl diets (0.4% or 6% NaCl), the decrease in α-ENaC abundance persisted, whereas the other changes were abolished. Analysis of serum aldosterone concentration in AT
1a
knockout mice and wild-type mice on the low NaCl diet revealed the absence of a decrease with AT
1a
gene deletion (11.8±2.3 nmol/L for knockout mice and 5.7±0.8 nmol/L for wild-type mice [significantly increased]). These results reveal that the AT
1a
receptor plays an important role in regulation of Na
+
transporter and channel proteins in the “post-macula densa” region of the renal tubule via a mechanism that is not dependent on altered circulating aldosterone concentrations.
Nitric Oxide Induces Dilation of Rat Aorta via Inhibition of Rho-Kinase Signaling
Authors: Chitaley Kanchan , Webb R. Clinton
Published: July 2002

NO induces vasodilation through cGMP-dependent protein kinase–dependent and –independent mechanisms. A recent study demonstrated that recombinant cGMP-dependent protein kinase can phosphorylate the small G protein, RhoA, thus inhibiting its activity. Additionally, sodium nitroprusside was found to reverse the phenylephrine-induced translocation of RhoA, which is further indicative of the inhibition of RhoA activity. RhoA is known to be involved in the Ca
2+
sensitization of vascular smooth muscle through the actions of one of its downstream effectors, Rho-kinase. This study examined whether NO endogenously induces the relaxation of intact rat aorta via the inhibition of the Rho-kinase–mediated Ca
2+
-sensitizing pathway. Endogenous Rho-kinase inhibitor activity was inhibited by the selective compound Y-27632. Treatment of endothelium-intact rat aorta with Y-27632 (1 μmol/L) resulted in an attenuation of maximal force generated in response to phenylephrine. In endothelium-denuded rings, however, 1 μmol/L Y-27632 was ineffective at inhibiting the phenylephrine-induced contraction. Additionally, 1 μmol/L Y-27632 was significantly less effective at inhibiting the phenylephrine-induced contraction of endothelium-intact rings in the presence of inhibitors of NO synthase or guanylate cyclase (
N
ω
-nitro-
l
-arginine and 1
H
-[1,2,4]oxadiazolo-[4,3-
a
]quinoxalin-1-one, respectively). Interestingly, sodium nitroprusside restored the ability of 1 μmol/L Y-27632 to attenuate phenylephrine-induced contraction. Rho-kinase inhibition was also found to increase the sensitivity of the endothelium-denuded aorta to sodium nitroprusside. These data demonstrate that NO inhibits Rho-kinase activity in the intact rat aorta, supporting the hypothesis that endogenous NO-mediated vasodilation occurs through the inhibition of Rho-kinase constrictor activity in the intact rat aorta.
Increased Methylglyoxal and Oxidative Stress in Hypertensive Rat Vascular Smooth Muscle Cells
Authors: Wu Lingyun , Juurlink Bernhard H.J.
Published: July 2002

Methylglyoxal can yield advanced glycation end products via nonenzymatic glycation of proteins. Whether methylglyoxal contributes to the pathogenesis of hypertension has not been clear. The aim of the present study was to investigate whether the levels of methylglyoxal and methylglyoxal-induced advanced glycation end products were enhanced and whether methylglyoxal increased oxidative stress, activated nuclear factor–κB (NF-κB), and increased intracellular adhesion molecule-1 (ICAM-1) content in vascular smooth muscle cells from spontaneously hypertensive rats. Basal cellular levels of methylglyoxal and advanced glycation end products were more than 2-fold higher (
P
<0.05) in cells from hypertensive rats than from normotensive Wistar-Kyoto rats. This correlated with levels of oxidative stress and oxidized glutathione that were significantly higher in cells from hypertensive rats, whereas levels of glutathione and activities of glutathione reductase and glutathione peroxidase were significantly lower. Basal levels of nuclearly localized NF-κB p65 and ICAM-1 protein expression were higher in cells from hypertensive rats than from normotensive rats. Addition of exogenous methylglyoxal to the cultures induced a greater increase in oxidative stress and advanced glycation end products in cells from hypertensive rats compared with normotensive rats and significantly decreased the activities of glutathione reductase and glutathione peroxidase in cells of both rat strains. Methylglyoxal activated NF-κB p65 and increased ICAM-1 expression in hypertensive cells, which was inhibited by
N
-acetylcysteine. Our study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methylglyoxal increases oxidative stress, activates NF-κB, and enhances ICAM-1 expression. Our findings suggest that that elevated methylglyoxal and associated oxidative stress possibly contribute to the pathogenesis of hypertension.
Alteration of Plasma Ghrelin Levels Associated With the Blood Pressure in Pregnancy
Authors: Makino Yasuo , Hosoda Hiroshi , Shibata Kazuhiko , Makino Ikuko , Kojima Masayasu , Kangawa Kenji , Kawarabayashi Tatsuhiko
Published: July 2002

Ghrelin, an endogenous ligand for the growth hormone secretagogues, was originally isolated from rat stomach. It stimulates the release of growth hormone from primary pituitary cell cultures. We investigated the plasma concentration of ghrelin peptide in 16 nonpregnant women, 18 normal pregnant women, 20 patients with pregnancy-induced hypertension, and 10 postpartum women. The plasma concentration of ghrelin in nonpregnant women was 239.5±16.9 fmol/mL. The plasma concentration of ghrelin in normal pregnant women at the third trimester was 127.1±5.6 fmol/mL. There was negative correlation between plasma ghrelin concentration and systemic blood pressure in normal pregnant women (systolic:
r
=−0.564,
P
<0.05; diastolic:
r
=−0.610,
P
<0.01). Pregnant women with pregnancy-induced hypertension (177.9±14.6 fmol/mL,
P
<0.05) also had significantly higher levels of ghrelin compared with those of normal pregnant women. In addition, there was a significant correlation between plasma ghrelin levels and systemic blood pressure (systolic:
r
=−0.482,
P
<0.05; diastolic:
r
=−0.466,
P
<0.05). These results suggest for the first time that ghrelin might have some role in cardiovascular control during normal pregnancy and in pathophysiological conditions in pregnancy, such as pregnancy-induced hypertension.
Vascular Smooth Muscle Cell Activation by Glycated Albumin (Amadori Adducts)
Authors: Hattori Yoshiyuki , Suzuki Manabu , Hattori Sachiko , Kasai Kikuo
Published: July 2002

Nonenzymatic glycation is increased in diabetes. The role of advanced glycation end products has been implicated in many of the complications of diabetes, whereas the effects of early-glycation Amadori-modified proteins on vascular cells alone are poorly defined. In the present study, we show that glycated serum albumin (GSA) induces a parallel activation of the redox-responsive transcription factors (nuclear factor κB) and AP-1 and increases activity of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38 MAPK in vascular smooth muscle cells (VSMCs). GSA increased expression of early response genes, c-
fos
and c-
jun
, and inflammatory genes, monocyte chemoattractant peptide (MCP-1), and interleukin (IL)-6. These effects were comparable to bacterial lipopolysaccharide, tumor necrosis factor-αa, (TNF-αa), IL-1αb, angiotensin II, epidermal growth factor, and the phorbol ester PMA. One of signaling pathways by which GSA activates VSMCs appears to be via nuclear factor κB activation, leading to induction of MCP-1 and IL-6 gene expression, comparable to the effects of lipopolysaccharide, TNF-αa, and IL-1αb. Another signaling cascade by which GSA activates VSMCs is the ERK→c-Fos→AP-1 pathway, which may lead to stimulation of cell proliferation and migration. These effects are comparable to the effects of angiotensin II, epidermal growth factor, and PMA. Incubation of VSMCs with the antioxidant
N
-acetylcysteine suppressed GSA-elicited mRNA induction of MCP-1 and IL-6. Inhibition of p38 MAPK but not ERK caused attenuation of MCP-1 and IL-6 mRNA induction. Finally, GSA caused a significant stimulation of VSMC growth and migration. These findings suggest that GSA may play a role in diabetic atherogenesis by activating VSMCs, leading to induction of inflammatory mediators in the vessel wall, as well as proliferation and migration of VSMCs.
The Foreign Imposition of Domestic Institutions
Authors: Owen John M.
Published: July 2002

International relations research has paid little attention to why states often spend precious resources building and maintaining domestic institutions in other states. I identify 198 cases offorcibledomestic institutional promotion, the most costly form of such interventions, between 1555 and 2000. I note several patterns in the data: these interventions come in three historical clusters; they are carried out by states of several regime types; states engage in the practice repeatedly; target states tend to be undergoing internal instability; states tend to promote their own institutions; and targets tend to be of strategic importance. The most intensive periods of promotion coincide with high transnational ideological tension and high international insecurity. I argue that these two conditions interact: forcible promotion is most likely when great powers (1) need to expand their power; and (2) find that, by imposing on in smaller states those institutions most likely to keep their ideological confreres in power, they can bring those states under their influence. Although in periods of high insecurity domestic variables alone may account for institutional impositions, such impositions may nonetheless extend the promoting states' influence and thereby alter the balance of international power.
Covert Auditory Attention Generates Activation in the Rostral/Dorsal Anterior Cingulate Cortex
Authors: Benedict Ralph H. B. , Shucard David W. , Maria Michael P. Santa , Shucard Janet L. , Abara Jose P. , Coad Mary Lou , Wack David , Sawusch James , Lockwood Alan
Published: July 2002

The anterior cingulate cortex (ACC) is believed to mediate conscious information processing or high-capacity attention. However, previous functional imaging studies have largely relied on tasks that involve motor function as well as attention. The work from our group utilizing an auditory continuous performance task demonstrated increased activity in a caudal division of the ACC that borders the supplementary motor area (SMA). Activity in this region was attributed to motor responding as well as attention. In the present study, we used15O H2O positron emission tomography (PET) to map brain activation during nonmotor, covert auditory attention. Our hypothesis was that a different region within the ACC, anterior to the SMA, would be active during covert attention (CA). Six men and six women were asked to monitor aurally presented syllables presented at a 1-sec interstimulus interval. During the CA condition, subjects were asked to continuously discriminate target (.19 probability) from nontarget stimuli. Simultaneous recording of event-related potentials (ERPs) confirmed the discrimination of target and nontarget stimuli and the allocation of attention capacity. Comparison of the monitored versus nonmonitored presentation of stimuli demonstrated significant activity in a rostral/dorsal division of the right ACC, anterior to SMA. Other regions of activation included the lateral prefrontal cortex and posterior superior temporal gyrus in the left hemisphere, consistent with neurocognitive models of language and vigilance. We conclude that a rostral/dorsal subdivision of the right ACC is specific for conscious attention during auditory processing, in contrast to premotor response formation.
A Neural Model of Perceptual-Motor Alignment
Authors: Guigon Emmanuel , Baraduc Pierre
Published: July 2002

Sensorimotor systems face complex and frequent discrepancies among spatial modalities, for example, growth, optical distortion, and telemanipulation. Adaptive mechanisms must act continuously to restore perceptual-motor alignments necessary for perception of a coherent world. Experimental manipulations that exposed participants to localized discrepancies showed that adaptation is revealed by the acquisition of a constrained relation between entire modalities rather than associations between individual exemplars within these modalities. The computational problem faced by the human nervous system can thus be conceived as having to induce constrained relations between continuous stimulus and response dimensions from ambiguous or incomplete training sets, that is, performing interpolation and extrapolation. How biological neuronal networks solve this problem is unknown. Here we show that neural processing based on linear collective computation and least-square (LS) error learning in populations of frequency-coded neurons (i.e., whose discharge varies in a monotonic fashion with a parameter) has built-in interpolation and extrapolation capacities. This model can account for the properties of perceptual-motor adaptations in sensorimotor systems.
CCCP Algorithms to Minimize the Bethe and Kikuchi Free Energies: Convergent Alternatives to Belief Propagation
Authors: Yuille A. L.
Published: July 2002

This article introduces a class of discrete iterative algorithms that are provably convergent alternatives to belief propagation (BP) and generalized belief propagation (GBP). Our work builds on recent results by Yedidia, Freeman, and Weiss (2000), who showed that the fixed points of BP and GBP algorithms correspond to extrema of the Bethe and Kikuchi free energies, respectively. We obtain two algorithms by applying CCCP to the Bethe and Kikuchi free energies, respectively (CCCP is a procedure, introduced here, for obtaining discrete iterative algorithms by decomposing a cost function into a concave and a convex part). We implement our CCCP algorithms on two- and three-dimensional spin glasses and compare their results to BP and GBP. Our simulations show that the CCCP algorithms are stable and converge very quickly (the speed of CCCP is similar to that of BP and GBP). Unlike CCCP, BP will often not converge for these problems (GBP usually, but not always, converges). The results found by CCCP applied to the Bethe or Kikuchi free energies are equivalent, or slightly better than, those found by BP or GBP, respectively (when BP and GBP converge). Note that for these, and other problems, BP and GBP give very accurate results (see Yedidia et al., 2000), and failure to converge is their major error mode. Finally, we point out that our algorithms have a large range of inference and learning applications.
Fast Curvature Matrix-Vector Products for Second-Order Gradient Descent
Authors: Schraudolph Nicol N.
Published: July 2002

We propose a generic method for iteratively approximating various second-order gradient steps—-Newton, Gauss-Newton, Levenberg-Marquardt, and natural gradient—-in linear time per iteration, using special curvature matrix-vector products that can be computed in O(n). Two recent acceleration techniques for on-line learning, matrix momentum and stochastic meta-descent (SMD), implement this approach. Since both were originally derived by very different routes, this offers fresh insight into their operation, resulting in further improvements to SMD.
Psychophysiological Correlates of Virtual Reality: A Review
Authors: Pugnetti Luigi , Meehan Michael , Mendozzi Laura
Published: July 2002

The recording and measurement of central and peripheral nervous system responses can provide important information during the development and the application of virtual reality (VR). Although studies on electroencephalographic, evoked potentials, and peripheral psychophysiological changes in connection with VR exposure are still preliminary, they show that reliable data can be obtained even in immersive VR conditions. There is no firm evidence that neurophysiological equipment—sensors and cables—may increase subjects' discomfort and affect their ability to interact with the virtual environments, but additional study is needed to clarify this issue. Suggestions as to how to limit potential interferences are summarized here. Two main lines of research are emerging: one seeking psychophysiological correlates of reaction and adaptation to stimuli and task variables in an attempt to understand more about human-VR interaction, and the other looking for ways to use psychophysiological responses to automatically control aspects of the virtual environments or other external devices. The main results emerging from the first group of studies indicate that psychophysiological measures of brain activity—notably EEG and event-related responses—may be used to distingush between automatic and controlled modes of processing. Additionally, peripheral measures, notably skin-resistance levels, are proposed as objective correlates of presence and of the outcome of specific VR-based desensitization therapies. There is no clear-cut evidence that brain waves may index unwanted effects on the central nervous system of VR exposure, but this issue deserves further study. The results of the second line of research seem to indicate that VR-induced psychophysiological responses can be used to develop assistive devices for people with disabilities or to control hands-free interaction within any virtual environment (for example, in highly demanding conditions). A related and promising field of application is that of neurofeedback, wherein VR may play an important role in increasing the motivational/ attentional span of clients, and, ultimately, the effectiveness of treatment protocols. Given these premises, it is suggested that research on psychophysiological correlates of VR should be incremented along the lines already delineated and possibly include also groups of subjects at risk for adverse affects.
Virtual Environment for Topographical Orientation (VETO): Clinical Rationale and Technical Characteristics
Authors: Bertella Laura , Marchi Stefano , Riva Giuseppe
Published: July 2002

The lack of spatial orientation often serves as a warning light for a diffused cerebral impairment, such as the one at the origin of a confusional state or of a mental disorder. Topographical orientation disorders may be the expression of memory or attention deficits, unilateral spatial negligence, or elementary visuoperceptive disorders. In a minority of cases, spatial disorientation presents as an isolated disorder and is the expression of a focal brain lesion.

The paper describes the clinical rationale and the technical characteristics of the Virtual Environment for Topographical Orientation (VETO). VETO is used both as a complementary tool for the assessment of topographical orientation disorders and to increase the possibilities of management of these patients from a rehabilitative point of view.

VETO is based on the recent theoretical model of wayfinding in virtual environments proposed by Chen and Stanney (1999). This model suggests that wayfinders generally start from the direct perception of the environment or from the recall of a cognitive map. In terms of direct perception of the environment, landmark knowledge is acquired by directly viewing indirect representation such as photographs. In terms of cognitive mapping, procedure/route knowledge is acquired through direct experience or through simulated experience and stored in memory.

Our hypothesis is that the study of spatial orientation through specific VETO tasks, both in normal samples and in subjects affected by topographical disorientation, can bring greater comprehension and validation of the cognitive models of spatial orientation present in literature.
Environmental Change and Foreign Policy: A Survey of Theory
Authors: Barkdull John , Harris Paul G.
Published: July 2002

Acomprehensive understanding of international environmental politics re quires attention to foreign policy. In this essay we describe a wide range of theories and approaches to foreign policy and international relations, with emphasis on how they can help us to better understand foreign policy in the environmental issue area. We organize the theories into three categories: systemic theories, which emphasize the influence of the international system, including the distribution of power within it; societal theories, which focus our attention on domestic politics and culture; and state-centric theories, which find answers to questions about foreign policy within the structure of the state and the individuals who promulgate and implement foreign policies in the name of a given country. Within this presentation of various theories, we highlight the influence of power, interests and ideas.
THE SETUPATIS, THE DUTCH, AND OTHER BANDITS IN EIGHTEENTH-CENTURY RAMNAD (SOUTH INDIA)
Authors: Bes Lennart
Published: July 2002

In Ramnad, bandits could be king. The open-ended political culture of this South Indian kingdom presented even people on the margins of society with opportunities to attain political power. Likewise, the VOC (Dutch East India Company), operating from the coastal frontier of the kingdom, played a significant role in the political arena of Ramnad. Given this similarity, it may be asked whether the Dutch were regarded as neutral outsiders (as they themselves thought they were) or rather as an indigenous marginal power. By comparing the internal and regional relations of Ramnad with its contacts with the VOC, this article attempts to determine the kingdom's perception of the Company. In Ramnad, could the Dutch be bandits? En Ramnad, un royaume dans l'Inde méridional, il arrive que le bandit se fait roi. La culture politique, ainsi que les avenues du pouvoir y furent en principe ouvertes à tous; aux marginaux indigènes, vivants dans les terres sèches périphériques, autant qu'aux fonctionnaires de la compagnie néerlandaise des Indes Orientales, la VOC, qui avait un comptoir sur le littoral. Elle se considerait neutre. Toutefois elle allait jouer un rôle important dans l'arène politique de Ramnad. Or, au niveau conceptuel la question se pose si la perspective indigène différenciait entre le roturier indigène d'au-delà de la terre de grande culture, et l'aventurier étranger, ou par contre les confondait l'un l'autre. Cet article se propose d'y voir plus clair par l'étude des liens internes et régionals entretenus par le centre politique de Ramnad, en comparant ceux-ci avec les relations vis-à-vis la VOC pour en déduire le statut social des Hollandais dans la société indigène.
The Reductionist and Compatibilist Argument of Epicurus' On Nature, Book 25
Authors: O'Keefe Tim
Published: July 2002

Epicurus' On Nature 25 is the key text for anti-reductionist interpretations of Epicurus' philosophy of mind. In it, Epicurus is trying to argue against those, like Democritus, who say that everything occurs 'of necessity,' and in the course of this argument, he says many things that appear to conflict with an Identity Theory of Mind and with causal determinism. In this paper, I engage in a close reading of this text in order to show that it does not contain any clear statement of either a doctrine of radically emergent properties and "downwards causation" (contra David Sedley) or of the non-reducibility of the mental to the atomic (contra Julia Annas). I argue that Epicurus' main thesis is that we cannot consistently argue against our conception of ourselves as rational agents, and that it is our reason that allows us to reform our characters, control our actions, and blame and praise one another appropriately. The way that Epicurus describes the development and causal efficacy of reason in On Nature book 25 is consistent both with reductionism and (more surprisingly) with causal determinism.
Death of a Companion Cat or Dog and Human Bereavement: Psychosocial Variables
Authors: Stokes Shelley , Planchon Lynn , Templer Donald , Keller Jacqueline
Published: July 2002

This study found that death depression, general depression, and positive attitudes toward, and attachment to, companion animals were associated with greater grief following the death of cats and dogs both in a veterinary client group who had recently lost their companion animals and in a college student group with a history of companion animal loss. The correlations of both the above variables and the demographic and death circumstance variables tended to be higher with the veterinary clients. Death of a dog by accident as opposed to illness correlated .81 with extended grief in the veterinary clients. Not having their dogs euthanized correlated .70 with extended grief in this group as well.
IMPLIED ANTECEDENTS IN JOB XL 2B AND PROVERBS III 6A
Authors: Johnson Timothy
Published: July 2002

This article proposes a solution for identifying two problematic antecedents in two separate verses of the Hebrew Bible. I suggest that these antecedents are implied nouns instead of specific nouns standing in the text. The first example of this occurs in Job lx 2b where the third person singular feminine suffix refers to an implied noun that is associated with a nearby participle. The second more controversial example is found in Prov. iii 6a. Here the LXX, whose antecedent is an implied noun, serves as the necessary guide for opening the way to understanding the MT, where another implied noun is used. In each verse, clarity of interpretation is gained, with the latter analysis resulting in a more severe break from traditional views.