bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Homocysteine Concentration, C677T
MTHFR
Genotype, and 844ins68bp
CBS
Genotype in Young Adults With Spontaneous Cervical Artery Dissection and Atherothrombotic Stroke
Authors: Pezzini Alessandro , Del Zotto Elisabetta , Archetti Silvana , Negrini Riccardo , Bani Paolo , Albertini Alberto , Grassi Mario , Assanelli Deodato , Gasparotti Roberto , Vignolo Luigi Amedeo , Magoni Mauro , Padovani Alessandro
Published: July 2002

Background and Purpose

—

The role of mild hyperhomocysteinemia as a risk factor for cerebral ischemia may depend on stroke subtype. To test this hypothesis, we undertook a prospective case-control study of a group of patients with spontaneous cervical artery dissection (sCAD), a group of patients with atherothrombotic stroke (non-CAD), and a group of control subjects.

Methods

—

Fasting total plasma homocysteine (tHcy) concentration, C677T
MTHFR
genotype, and 844ins68bp
CBS
genotype were determined in 25 patients with sCAD, 31 patients <45 years of age with non-CAD ischemic stroke, and 36 control subjects. Biochemical data in the patient groups were obtained within the first 72 hours of stroke onset.

Results

—

Median tHcy levels were significantly higher in patients with sCAD (13.2 μmol/L; range, 7 to 32.8 μmol/L) compared with control subjects (8.9 μmol/L; range, 5 to 17.3 μmol/L; 95% CI, 1.05 to 1.52;
P
=0.006). Cases with tHcy concentration above the cutoff level of 12 μmol/L were significantly more represented in the group of patients with sCAD compared with control subjects (64% versus 13.9%; 95% CI, 2.25 to 44.23;
P
=0.003); a significant association between the
MTHFR TT
genotype and sCAD was also observed (36% versus 11.1%; 95% CI, 1.10 to 19.23;
P
=0.045). No significant difference in tHcy levels and in the prevalence of thermolabile
MTHFR
was found between patients with non-CAD ischemic stroke and control subjects and between patients with sCAD and non-CAD ischemic stroke. The distribution of the 844ins68bp
CBS
genotype and the prevalence of subjects carrying both the
TT MTHFR
and 844ins68bp
CBS
genotypes were not significantly different among the 3 groups.

Conclusions

—

Our results are consistent with the hypothesis that increased plasma homocysteine levels and the
TT MTHFR
genotype may represent risk factors for sCAD. In contrast, their role in atherothrombotic strokes remains a contentious issue.
Hypoxic-Ischemic Injury Induces Macrophage Inflammatory Protein-1α Expression in Immature Rat Brain
Authors: Cowell Rita M. , Xu Haiyan , Galasso John M. , Silverstein Faye S.
Published: July 2002

Background and Purpose

—

Macrophage inflammatory protein (MIP)-1α is a well-characterized monocyte chemoattractant; its role in regulating monocyte and microglial recruitment and activation in the injured neonatal brain is unknown. We evaluated the impact of acute hypoxic-ischemic (HI) brain injury on the expression of MIP-1α in neonatal rat brain.

Methods

—

To elicit forebrain ischemic injury, 7-day-old (P7) rats underwent right carotid ligation, followed by 2.5 hours of 8% oxygen exposure. We used an enzyme-linked immunosorbent assay and immunohistochemistry to detect MIP-1α; double-labeling immunofluorescence assays were analyzed with confocal microscopy to identify cellular sources of MIP-1α. Immunocytochemistry assays were also used to detect 2 MIP-1α receptors, CCR1 and CCR5.

Results

—

We found marked increases in tissue concentrations of MIP-1α in the HI cerebral hemisphere, peaking from 8 to 72 hours after lesioning. Immunocytochemistry assays revealed that MIP-1α was constitutively expressed in physiologically activated microglia; from 8 to 120 hours after lesioning, MIP-1α immunoreactive monocytes and microglia accumulated in the lesion territory. In immunoreactive cells, MIP-1α was diffusely distributed throughout the cytoplasm at early post-HI time intervals; by 72 hours, MIP-1α immunoreactivity was typically concentrated adjacent to the nucleus, a pattern indicative of active MIP-1α production. In P7 to P12 brain, many cells expressed MIP-1α receptors; both CCR1 and CCR5 immunoreactivity were localized to endothelium and ependyma; CCR1-immunoreactive astrocytes and neurons and CCR5-immunoreactive microglia were also identified.

Conclusions

—

These data implicate MIP-1α as a mediator of the complex and sustained inflammatory response initiated by perinatal HI braininjury.
Body Height Is Associated With Decreased Long-Term Stroke but Not Coronary Heart Disease Mortality?
Authors: Goldbourt Uri , Tanne David
Published: July 2002

Background and Purpose
—

There is disagreement whether shorter persons suffer increased rates of coronary heart disease (CHD) or stroke. Potential mechanisms for such associations are not well understood. We used findings from a cohort study, in which 10 000 Israeli men were followed up, to examine the associations between stature and fatal CHD as well as fatal stroke.

Methods
—

The cohort was composed of 10 059 men aged ≥40 years who were tenured civil servants or municipal employees. They were followed up for mortality over 23 years (1963 to 1986), for a total of 203 452 person-years of follow-up. We divided men by their height, as measured in the baseline (1963) examinations, into quartiles (≤162 cm, 163 to 167 cm, 168 to 171 cm, and ≥172 cm).

Results
—

During the follow-up period, 1098 men died of CHD, and 364 men died of stroke. Height and weight had been measured for 10 034 men, including all but 1 of the deceased. In contrast to the finding of little variation of CHD death rates between different quartiles of body height, a clear significant pattern of declining stroke mortality (slightly reduced by age adjustment) was observed with increasing body height, with rates of 46, 36, 33, and 29 per 1000 men with increasing height quartiles, respectively (
P
=0.002 for linear trend). The estimated age-adjusted hazard risk of stroke mortality associated with a 5-cm decrement in height was 1.13 (95% CI 1.04 to 1.22). The respective risk associated with being at the shortest quartile versus the tallest one was 1.54 (95% CI 1.13 to 2.10). Adjustment for socioeconomic status, a predictor of stroke in this cohort, for antihypertensive therapy and for established predictors of stroke (blood pressure, smoking, and diabetes) did not alter these findings.

Conclusions
—

Height, a potential strong indicator of nutritional status, may be inversely associated with the long-term incidence of fatal stroke in a way that remains to be elucidated.
Are Spontaneous Cerebral Microemboli Consistent in Carotid Disease?
Authors: Hutchinson Suzanne , Riding Graham , Coull Stuart , McCollum Charles N.
Published: July 2002

Background and Purpose

—

Transcranial Doppler may be used to detect spontaneous cerebral emboli (SCE), but this information will only identify at-risk patients if these individuals are consistently identified over time. We investigated the consistency of SCE production in patients with symptomatic carotid disease.

Methods

—

Transcranial Doppler signals from the ipsilateral middle cerebral artery in 25 patients with symptomatic carotid stenosis of >70% were recorded over 1 hour for blind analysis by a panel of trained observers. This was repeated at the same time of day, weekly, for 6 weeks.

Results

—

The number of patients with SCE increased with each week of monitoring until 13 (52%) were positive. The range of the cumulative number of SCE was 1 to 6. Ten (40%) patients were positive for SCE during only 1 monitoring session, and 2 (8%) were positive for SCE during 2 sessions. SCE-positive patients tended to have more recent symptoms. The correlation coefficients between time elapsed since last cerebral symptom and SCE were weak and not significant.

Conclusions

—

Most, if not all, patients with severe carotid disease will eventually produce SCE. However, the production of an SCE is random, and it is likely that many hours of monitoring are required to determine whether a patient with symptomatic carotid disease is SCE positive. SCE are unlikely to identify at-risk patients but may indicate periods of transiently increased risk in individual patients.
Microembolus Detection in Patients With Takayasu’s Arteritis
Authors: Kumral Emre , Evyapan Dilek , Aksu Kenan , Keser Gökhan , Kabasakal Yasemin , Balkir Kaan
Published: July 2002

Background and Purpose
—

Takayasu’s arteritis (TA) is a chronic inflammatory disease of unknown etiology that can affect the aorta and its branches. The cerebral ischemia in TA can be caused by a variety of mechanisms, and the focus of this study is to detect the possible contribution of microembolus in the pathogenesis of stroke.

Methods
—

Eighteen patients with TA according to the criteria for the classification of TA of the American College of Rheumatology and 100 age-matched healthy controls were studied. Both middle cerebral arteries were monitored by transcranial Doppler (TCD) ultrasound for at least 30 minutes. All patients with TA were followed up for a mean duration of 2.1 months, and recurrent strokes were registered.

Results
—

Microembolic signals (MES) were present in 22% of the patients overall, and the intensity of the MES varied between 9 and 30 dB. Moreover, MES were found in 30% of the patients with higher erythrocyte sedimentation rate. Two (67%) of 3 patients who did not receive any treatment had MES, but only 2 (13%) of 15 patients who received immunosuppressive and anticoagulant therapy before the TCD ultrasonography monitoring had MES. During the follow-up period after MES recording, we did not observe any recurrent stroke.

Conclusions
—

TCD ultrasonography monitoring can be used as an additional noninvasive procedure to detect microembolus in patients with TA during the acute and chronic phase of the disease. The monitoring of MES may also help in choosing better treatment for the long-term prophylaxis of the disease from acute ischemic stroke, but further large studies are required to justify the efficacy of immunosuppressive treatment in these patients.
Dependence of Early Cerebral Reperfusion and Long-Term Outcome on Resuscitation Efficiency After Cardiac Arrest in Rats
Authors: Xu Yan , Liachenko Serguei , Tang Pei
Published: July 2002

Background and Purpose

—

While it is well known that longer duration of cardiac arrest (CA) is often associated with poorer long-term outcome, the influence of resuscitation efficacy on postischemia recovery is less clear. The objective of the present study is to investigate whether an inadequate and prolonged resuscitation after a shorter CA can lead to worse long-term outcomes than an effective resuscitation after a longer CA, provided that the total time from the onset of CA to the return of spontaneous circulation is comparable.

Methods

—

Thirty-eight rats were randomized into 2 groups with nominal 9 minutes (group 1) and 15 minutes (group 2) of normothermic asphyxial CA. Each group was further divided into 2 subgroups on the basis of the duration of resuscitation efforts (labeled as S and L for short and long, respectively). Thus, the asphyxia and nominal resuscitation times were 8 and 1 minute, respectively, for group 1S, 5 and 4 minutes for group 1L, 14 and 1 minute for group 2S, and 11 and 4 minutes for group 2L. Cerebral perfusion was measured continuously at the dorsal hippocampus level before, during, and after the CA, with the use of the arterial spin labeling MRI technique. The survival time, histological damage, and neurological deficit were evaluated 5 days after resuscitation.

Results

—

Groups 1S and 1L had nearly the same duration of CA (9.02±0.17 minutes, n=6 versus 8.58±0.80 minutes, n=6). The same is true for groups 2S and 2L (15.51±0.59 minutes, n=11 versus 15.65±1.25 minutes, n=15). Despite longer asphyxia, shorter and more effective resuscitation was associated with significantly improved long-term outcomes and higher cerebral perfusion at the early stage of reperfusion.

Conclusions

—

Effective resuscitation increased early reperfusion and improved survival after CA. The clinical implication is that inadequate and prolonged resuscitation may have detrimental effects on the recovery of CA patients.
Blood Use in Cerebrovascular Neurosurgery
Authors: Couture Daniel E. , Ellegala Dilantha B. , Dumont Aaron S. , Mintz Paul D. , Kassell Neal F.
Published: July 2002

Background and Purpose

—

This study reviews the perioperative use of red blood cell transfusion in cerebrovascular neurosurgery. The current algorithm for preoperative ordering of red cells is historical and dated. More blood is ordered than is actually transfused, and considerable variability exists between different institutions. We determine the use of blood transfusion in cerebrovascular surgery to develop a rational blood ordering practice.

Methods

—

Records of 301 patients undergoing cerebrovascular neurosurgery at the University of Virginia were reviewed to quantitatively evaluate red blood cell transfusion practices. The amount and reason for transfusion were noted in each case.

Results

—

In 126 patients undergoing carotid endarterectomy, there were no preoperative or intraoperative transfusions and 5 postoperative transfusions (4.0%). In 71 ruptured aneurysm patients, there were 2 preoperative blood transfusions (2.8%), 4 intraoperative transfusions (5.6%), and 15 postoperative transfusions (21.1%). Forty-seven patients underwent surgery for unruptured aneurysms, with no preoperative transfusions, 2 intraoperative transfusions (4.3%), and 8 postoperative blood transfusions (17.0%). Of the 54 patients undergoing surgery for arteriovenous malformations, 5 patients (9.3%) were transfused preoperatively, 4 were transfused intraoperatively (7.4%), and 22 were transfused postoperatively (40.7%). None of the 3 patients undergoing surgery for concomitant arteriovenous malformations and aneurysms received intraoperative blood transfusions, but 1 received blood both preoperatively and postoperatively, and another received a transfusion postoperatively only. The overall ratio of perioperative cross-match to transfusion in this series is 41.4.

Conclusions

—

In vascular neurosurgery at our institution, blood has routinely been ordered excessively. We recommend an ABO-Rh type and antibody screen for aneurysm and arteriovenous malformation surgery and no screen for carotid endarterectomy to efficiently utilize transfusion therapy in cerebrovascular surgery.
Renal Interstitial Fluid Concentrations of Angiotensins I and II in Anesthetized Rats
Authors: Nishiyama Akira , Seth Dale M. , Navar L. Gabriel
Published: July 2002

Previous studies have indicated that angiotensin II (Ang II) concentrations in renal interstitial fluid are much higher than plasma levels. In the present study, we performed experiments to explore renal interstitial fluid concentrations of Ang I and Ang II further and to determine whether these levels are altered by acute arterial infusion of an ACE inhibitor (enalaprilat) or by volume expansion. Microdialysis probes (molecular weight cutoff point: 30 000 Da) were implanted in the renal cortex of anesthetized rats and were perfused at a rate of 2 μL/min. Using relative equilibrium rates, the basal renal interstitial fluid Ang II concentration averaged 3.07±0.43 nmol/L, a value much higher than the plasma Ang II concentration of 107±8 pmol/L (n=7). Interstitial fluid Ang I concentrations (0.84±0.04 nmol/L) were consistently lower than the Ang II concentrations but higher than the plasma Ang I concentrations (112±14 pmol/L). Intra-arterial infusion of enalaprilat (7.5 μmol/kg/min, n=5) for 120 minutes resulted in a significant decrease in mean arterial pressure (from 114±4 to 68±4 mm Hg) along with reductions in plasma and renal ACE activity (by −99% and −52%, respectively). Enalaprilat resulted in a significant increase in plasma Ang I from 133±21 to 1167±328 pmol/L and a decrease in plasma Ang II from 110±12 to 67±9 pmol/L. During enalaprilat infusion, interstitial fluid concentration of Ang I was significantly increased from 0.78±0.06 to 0.97±0.08 nmol/L; however, Ang II concentrations were not altered significantly (3.67±0.28 versus 3.67±0.25 nmol/L). Acute volume loading with Ringer’s solution containing 1% bovine serum albumin at a rate of 150 μL/min for 2 hours (6% to 7% of body weight) lowered plasma concentrations of Ang I from 110±23 to 16±2 pmol/L and Ang II from 100±23 to 36±6 pmol/L; however, renal interstitial fluid concentrations of Ang I and Ang II were not altered significantly during volume expansion (Ang I, from 0.77±0.05 to 0.69±0.03 nmol/L; Ang II, from 3.76±0.43 to 3.59±0.39 nmol/L, n=5). These data indicate that renal interstitial fluid concentrations of Ang I and Ang II are substantially higher than the corresponding plasma concentrations. Furthermore, the fact that the high interstitial fluid concentrations of Ang II are not responsive to acute ACE inhibition or volume expansion suggests the compartmentalization and independent regulation of renal interstitial fluid Ang II.
Activation of Leukocytes During the Uteroplacental Passage in Preeclampsia
Authors: Mellembakken Jan Roar , Aukrust Pål , Olafsen Mette Kløvstad , Ueland Thor , Hestdal Kjetil , Videm Vibeke
Published: July 2002

Endothelial dysfunction and inflammation appear to play a major role in the pathogenesis of preeclampsia. We hypothesize that a chronic inflammation in the decidua and placenta during preeclampsia may lead to a local leukocyte activation in this compartment. Venous blood was sampled simultaneously from antecubital and uterine veins during cesarean sections in 30 women with preeclampsia, 29 with uncomplicated pregnancies, and from 17 nonpregnant women. The expression of adhesion molecules and complement-related markers on neutrophils and monocytes was analyzed by flow cytometry. In patients with preeclampsia, neutrophil expression of the integrins CD11a, CD11b, and CD11c and of the complement related markers CD35 and CD59 was significantly higher in samples from
uterine
than from
antecubital veins
. No differences were found in nonpregnant women. On monocytes the expression of the Sialyl Lewis
x
antigen, the integrins CD11a, CD11c, and CD49d, and the complement-related markers CD46 and CD59 was higher in samples from
uterine
than from
antecubital veins
during preeclampsia, but not in uncomplicated pregnancies, whereas in nonpregnant women CD31 was decreased. Our findings suggest activation of neutrophils and monocytes taking place during the uteroplacental passage in preeclamptic, but not in normal pregnancies. Such a local inflammatory response involving enhanced leukocyte/endothelial interaction may contribute to the pathogenesis of this disorder.
Selective Resistance to Central Neural Administration of Leptin in Agouti Obese Mice
Authors: Rahmouni Kamal , Haynes William G. , Morgan Donald A. , Mark Allyn L.
Published: July 2002

Abstract—

We recently demonstrated that in a rodent model of obesity (agouti yellow mice), there is a selective leptin resistance with preservation of the sympathetic actions despite loss of appetite and weight-reducing actions of systemic leptin. Here, we examined whether selective leptin resistance exists in agouti mice during central neural administration of leptin. In agouti obese mice and lean controls, we tested the effects of single intracerebroventricular (ICV) injection of leptin or vehicle on food intake and body weight in the conscious state and on renal sympathetic nerve activity during anesthesia. Agouti obese mice had higher (

P

<0.0001) mean arterial pressure (100±2 mm Hg) than lean controls (90±2 mm Hg). In lean controls (n=9 to 10), ICV leptin caused a dose-dependent decrease in body weight (

P

<0.001) and food intake (

P

<0.001). For example, ICV leptin (3 μg) decreased food intake and body weight, respectively, by 3.3±0.3 g (

P

<0.001) and 2.6±0.3 g (

P

<0.001) in lean mice. However, in agouti obese mice (n=9 to 10), ICV leptin did not significantly decrease food intake or body weight. ICV leptin caused in RSNA a significant and dose-dependent increase in renal sympathetic nerve activity that was of the same magnitude in the lean and agouti obese mice. The rise in renal sympathetic nerve activity induced by ICV leptin (3 μg) was 274±67% (

P

<0.001) in lean controls and 275±46% (

P

<0.001) in the agouti obese mice. In summary, this study indicates that selective leptin resistance in agouti obese mice occurs with central neural administration of leptin, suggesting that selective leptin resistance in this model is not due to a defect in leptin transport across the blood brain barrier. It seems to result instead from alterations in the central neural pathways mediating effects of leptin.
A
2B
Adenosine Receptors Stimulate Growth of Porcine and Rat Arterial Endothelial Cells
Authors: Dubey Raghvendra K. , Gillespie Delbert G. , Jackson Edwin K.
Published: July 2002

The goal of this study was to determine which adenosine receptor subtype mediates growth stimulation by adenosine in arterial endothelial cells. In porcine coronary artery and rat aortic endothelial cells, 2-chloroadenosine (Cl-Ad), a metabolically stable analog of adenosine, stimulated DNA synthesis (
3
H-thymidine incorporation), cellular proliferation (cell number), collagen synthesis (
3
H-proline incorporation), and cell migration. The growth effects of adenosine and Cl-Ad were mimicked by the adenosine receptor agonist 5′-N-methylcarboxamidoadenosine but not by the adenosine receptor agonists N
6
-cyclopentyladenosine, 4-aminobenzyl-5′-N-methylcarboxamidoadenosine or CGS21680, an agonist profile consistent with an A
2B
receptor-mediated effect. The adenosine receptor antagonists KF17837 and 1,3-dipropyl-8-
p
-sulfophenylxanthine but not 8-cyclopentyl-1,3-dipropylxanthine blocked the growth-stimulatory effects of Cl-Ad and 5′-N-methylcarboxamidoadenosine, an antagonist profile consistent with an A
2
receptor-mediated action. Treatment of endothelial cells with erythro-9-(2-hydroxy-3-nonyl) adenine plus iodotubericidin (inhibitors of adenosine deaminase and adenosine kinase, respectively) induced endothelial cell growth, and these effects were blocked by 1,3-dipropyl-8-
p
-sulfophenylxanthine and KF17837 but not 8-cyclopentyl-1,3-dipropylxanthine, suggesting that endothelial cell-derived adenosine induces growth via A
2
receptors. The growth-stimulatory effects of Cl-Ad, 5′-N-methylcarboxamidoadenosine, and erythro-9-(2-hydroxy-3-nonyl) adenine plus iodotubericidin were abolished by antisense but not scrambled or sense oligonucleotides to the A
2B
receptor. Our findings strongly support the hypothesis that adenosine induces endothelial cell growth by activating A
2B
receptors. Thus, A
2B
receptors may play a critical role in regulating vascular remodeling associated with endothelial cell proliferation in angiogenesis, collateral vessel development, and recovery after vascular injury. Pharmacological or molecular biological activation of A
2B
receptors may be useful in modulating vascular remodeling.
Interaction of O
2
−
and NO in the Thick Ascending Limb
Authors: Ortiz Pablo A. , Garvin Jeffrey L.
Published: July 2002

Abstract—

Nitric oxide (NO) is an important regulator of NaCl absorption by the thick ascending limb of the loop of Henle (THAL). The free radical superoxide (O
2
−
) reacts with NO, decreasing its bioavailability. O
2
−
is produced by mitochondria and various oxidases, some of which are present in the THAL. However, the ability of the THAL to produce O
2
−
and its interaction with NO have not been studied. We hypothesized that NO bioavailability is decreased by O
2
−
. THALs were isolated and perfused and NO production was measured with an NO-selective microelectrode. Addition of L-Arg (250 μmol/L), but not D-arginine, to the bath increased NO release by 34.8±11.8 pA (n=7). The response to L-Arg was completely abolished by the NO synthase inhibitor L-NAME (n=7). Scavenging THAL O
2
−
with the superoxide dismutase (SOD) mimetic Tempol (50 μmol/L) increased L-Arg-induced NO release. At all concentrations of L-Arg tested (50, 100, 250, 500, and 750 μmol/L), further addition of Tempol to the bath significantly increased NO release by THALs. Addition of SOD (300 U/mL) to the bath increased L-Arg-induced NO levels by 82% (n=5;

P

<0.02). Pretreatment of THALs with the SOD inhibitor diethyl-dithiocarbamate (250 μmol/L) blunted L-Arg-induced NO release by 63% compared with untreated tubules (n=5;

P

<0.05). Finally, we tested the effect of Tempol on NO-induced inhibition of THAL chloride transport. Addition of L-Arg decreased THAL Cl
−
absorption by 35%. Subsequent addition of Tempol (50 μmol/L) to the bath further decreased Cl
−
absorption by 35% (n=6;

P

<0.05). We conclude that NO bioavailability in the THAL is decreased by O
2
−
. In addition, we believe our studies are the first to show that endogenous O
2
−
may act as a physiological regulator of nephron NaCl transport.
Functional Significance of Activation of Calcium/Calmodulin–Dependent Protein Kinase II in Angiotensin II–Induced Vascular Hyperplasia and Hypertension
Authors: Muthalif Mubarack M. , Karzoun Nour A. , Benter Ibrahim F. , Gaber Lillian , Ljuca Farid , Uddin Mohammed R. , Khandekar Zinat , Estes Anne , Malik Kafait U.
Published: July 2002

We have reported that norepinephrine (NE) and angiotensin II (Ang II) increase CaM kinase II activity, which, in turn, activates cytosolic phospholipase A
2
(PLA
2
) and releases arachidonic acid. The products of arachidonic acid generated via cytochrome P-450 and lipoxygenase contribute to the development of hypertension and vascular smooth muscle cell (VSMC) hyperplasia. The purpose of this study was to investigate whether CaM kinase II contributes to VSMC proliferation elicited by NE and Ang II and to hypertension induced by Ang II. NE (1 μmol/L) and Ang II (1 μmol/L) increased proliferation of rabbit aortic VSMC as measured by increased [
3
H]-thymidine incorporation; this effect of NE and Ang II was attenuated 88±10% and 64±11% by the CaM kinase II inhibitor KN-93, respectively. Infusion of Ang II with miniosmotic pumps (350 ng/min for 6 days) in rats elevated mean arterial pressure (MABP), which was reduced by simultaneous infusion of KN-93 (578 ng/min, for 6 days) (Ang II alone: MABP =174±3 mm Hg, n=12 versus Ang II + KN-93: MABP 123±5 mm Hg, n=4,
P
<0.05). Administration of KN-93 as a single bolus injection (16 mg/Kg), but not its vehicle, in Ang II–infused hypertensive animals also decreased MABP from 179±9 mm Hg to 109±6 mm Hg (n=5,
P
<0.05). CaM kinase II activity was increased in the kidney of Ang II–infused hypertensive animals compared with normotensive controls. Treatment with KN-93 reduced CaM kinase II activity and ameliorated the intravascular injury in the kidneys of Ang II–infused hypertensive rats. Our data indicate that CaM kinase activation represents an important component of the mechanism(s) initiating VSMC proliferation and the development and maintenance of Ang II–induced hypertension in rat.
Phorbol Diacetate Potentiates Na
+
-K
+
ATPase Inhibition by a Putative Endogenous Ligand, Marinobufagenin
Authors: Fedorova Olga V. , Dorofeeva Natalia A. , Lopatin Denis A. , Lakatta Edward G. , Bagrov Alexei Y.
Published: July 2002

Several vasoconstrictor agents can regulate the phosphorylation status of the Na
+
-K
+
ATPase (NKA). We have recently demonstrated that mammalian tissues contain an endogenous bufadienolide, digitalis-like α
1
-NKA–selective ligand, marinobufagenin (MBG). Protein kinase C induces phosphorylation of the α
1
-NKA isoform, the major isoform in vascular smooth muscle, kidney, and heart cells. We hypothesized that protein kinase C–induced phosphorylation of NKA can potentiate the effect of endogenous digitalis-like ligands, and that such potentiation can occur in an NKA isoform–specific fashion. A protein kinase C activator, phorbol 12,13-diacetate (PDA, 50 nmol/L), induced phosphorylation of the α
1
-NKA from human mesenteric artery (HMA) sarcolemma and rat kidney but not that of the α
3
-NKA from rat fetal brain. In HMA sarcolemma, which predominantly contains α
1
-NKA, PDA (50 nmol/L) potentiated the NKA-inhibitory effect of MBG at the level of high-affinity binding sites (0.05±0.03 nmol/L versus 4.0±1.7 nmol/L,
P
<0.05). In contrast, PDA did not affect the NKA inhibition by ouabain, an α
3
-NKA ligand. In isolated endothelium-denuded HMA artery rings, 50 nmol/L PDA potentiated the MBG-induced vasoconstriction (EC
50
, 17±6 nmol/L versus 150±40 nmol/L;
P
<0.01). Our results suggest that α
1
-isoform–specific NKA inhibition by the endogenous digitalis-like ligand, MBG, is substantially enhanced via NKA phosphorylation by protein kinase C. Thus, an interaction of protein kinase C–dependent phosphorylation and MBG on NKA activity may underlie the synergistic vasoactive effects of MBG and other endogenous vasoconstrictors in hypertension.
Vasodilator Action of Angiotensin-(1-7) on Isolated Rabbit Afferent Arterioles
Authors: Ren YiLin , Garvin Jeffrey L. , Carretero Oscar A.
Published: July 2002

Recent studies have shown that angiotensin-(1-7) (Ang-[1-7]), which is generated endogenously from both Ang I and II, is a bioactive component of the renin-angiotensin system and may play an important role in the regulation of blood pressure. However, little is known about its role in regulating the reactivity of the afferent arteriole or the mechanism(s) involved. We hypothesized that Ang-(1-7), acting on specific receptors, participates in the control of afferent arteriole tone. We first examined the direct effect of Ang-(1-7) on rabbit afferent arterioles microperfused in vitro, and we tested whether endothelium-derived relaxing factor/NO and cyclooxygenase products are involved in its actions. To assess the vasodilator effect of Ang-(1-7), afferent arterioles were preconstricted with norepinephrine, and increasing concentrations of Ang-(1-7) were added to the lumen. We found that 10
−10
to 10
−6
mol/L Ang-(1-7) produced dose-dependent vasodilatation, increasing luminal diameter from 8.9±1.0 to 16.3±1.1 μm (
P
<0.006). Indomethacin had no effect on Ang-(1-7)–induced dilatation.

N
G

-nitro-
l
-arginine methyl ester, a NO synthesis inhibitor, abolished the dilatation induced by Ang-(1-7). We attempted to determine which angiotensin receptor subtype is involved in this process. We found that 10
−6
mol/L [d-Ala
7
]–Ang-(1-7), a potent and selective Ang-(1-7) antagonist, abolished the dilatation induced by Ang-(1-7). An angiotensin II type 1 receptor antagonist (L158809) and an angiotensin II type 2 receptor antagonist (PD 123319) at 10
−6
mol/L had no effect on Ang-(1-7)–induced dilatation. Our results show that Ang-(1-7) causes afferent arteriole dilatation. This effect may be due to production of NO, but not the action of cyclooxygenase products. Ang-(1-7) has a receptor-mediated vasodilator effect on the rabbit afferent arteriole. This effect may be mediated by Ang-(1-7) receptors, because angiotensin type 1 and type 2 receptor antagonists could not block Ang-(1-7)–induced dilatation. Thus, our data suggest that Ang-(1-7)opposes the action of Ang II and plays an important role in the regulation of renal hemodynamics.
Angiotensin II Type 2 Receptor Counter-Regulates Type 1 Receptor in Catecholamine Synthesis in Cultured Porcine Adrenal Medullary Chromaffin Cells
Authors: Takekoshi Kazuhiro , Ishii Kiyoaki , Shibuya Shunsuke , Kawakami Yasushi , Isobe Kazumasa , Nakai Toshiaki
Published: July 2002

We previously showed that CGP 42112 (an angiotensin type 2 [AT
2
] agonist) markedly reduces catecholamine biosynthesis by decreasing cGMP production mediated by AT
2
, a subtype of Ang II receptor that is dominantly expressed in cultured porcine chromaffin cells. To elucidate the relationship of the 2 types of Ang II receptors, angiotensin type 1 (AT
1
) and AT
2
, in the synthesis of catecholamine in adrenal medullary cells, we have examined the effect of Ang II plus CV-11974 (an AT
1
antagonist that selectively simulates AT
2
stimulation) and the effect of Ang II plus PD 123319 (an AT
2
antagonist that selectively simulates AT
1
stimulation) on catecholamine synthesis. We found that Ang II reduced cGMP production via AT
2
, in a similar manner to that found with CGP 42112. Stimulation of AT
1
significantly upregulated protein kinase C activity. Tyrosine hydroxylase (TH) is a rate-limiting enzyme involved in the biosynthesis of catecholamine, and this catecholamine synthesis depends both on TH enzyme activity and on the levels of TH protein after TH gene transcription. We found that AT
2
stimulation significantly inhibited TH enzyme activity, whereas AT
1
stimulation significantly upregulated TH enzyme activity. The stimulatory effect of AT
1
was completely inhibited by Ro-32-0432 (a protein kinase C inhibitor) and PD 98059 (a MAP kinase kinase-1 [MEK-1] inhibitor). Pretreatment of cells with either 8-Br-cGMP (a membrane-permeable cGMP analog) or Zaprinast (a phosphodiesterase inhibitor) abolished the inhibitory effect of AT
2
on TH enzyme activity, indicating that the stimulatory effect of AT
2
may be mediated through a reduction in cGMP concentration. Similar to the effect on TH enzyme activity, AT
2
stimulation significantly reduced TH mRNA and protein levels and net catecholamine content below basal levels, whereas AT
1
stimulation increased them. We confirmed these findings by gel mobility shift assay. Our results show that stimulation of AT
2
reduces catecholamine biosynthesis via a decrease in cGMP levels. In contrast, stimulation of AT
1
stimulates catecholamine biosynthesis through activation of PKC. Thus, we conclude that AT
1
and AT
2
have counter-regulatory roles in the synthesis of catecholamine in adrenal medullary chromaffin cells.
Abnormal Auditory Cortical Activation in Dyslexia 100 msec after Speech Onset
Authors: Helenius Päivi , Salmelin Riitta , Richardson Ulla , Leinonen Seija , Lyytinen Heikki
Published: July 2002

Reading difficulties are associated with problems in processing and manipulating speech sounds. Dyslexic individuals seem to have, for instance, difficulties in perceiving the length and identity of consonants. Using magnetoencephalography (MEG), we characterized the spatio-temporal pattern of auditory cortical activation in dyslexia evoked by three types of natural bisyllabic pseudowords (/ata/, /atta/, and /a a/), complex nonspeech sound pairs (corresponding to /atta/ and /a a/) and simple 1-kHz tones. The most robust difference between dyslexic and non-reading-impaired adults was seen in the left supratemporal auditory cortex 100 msec after the onset of the vowel /a/. This N100m response was abnormally strong in dyslexic individuals. For the complex nonspeech sounds and tone, the N100m response amplitudes were similar in dyslexic and nonimpaired individuals. The responses evoked by syllable /ta/ of the pseudoword /atta/ also showed modest latency differences between the two subject groups. The responses evoked by the corresponding nonspeech sounds did not differ between the two subject groups. Further, when the initial formant transition, that is, the consonant, was removed from the syllable /ta/, the N100m latency was normal in dyslexic individuals. Thus, it appears that dyslexia is reflected as abnormal activation of the auditory cortex already 100 msec after speech onset, manifested as abnormal response strengths for natural speech and as delays for speech sounds containing rapid frequency transition. These differences between the dyslexic and nonimpaired individuals also imply that the N100m response codes stimulus-specific features likely to be critical for speech perception. Which features of speech (or nonspeech stimuli) are critical in eliciting the abnormally strong N100m response in dyslexic individuals should be resolved in future studies.
A Monte Carlo EM Approach for Partially Observable Diffusion Processes: Theory and Applications to Neural Networks
Authors: Movellan Javier R. , Mineiro Paul , Williams R. J.
Published: July 2002

We present a Monte Carlo approach for training partially observable diffusion processes. We apply the approach to diffusion networks, a stochastic version of continuous recurrent neural networks. The approach is aimed at learning probability distributions of continuous paths, not just expected values. Interestingly, the relevant activation statistics used by the learning rule presented here are inner products in the Hilbert space of square integrable functions. These inner products can be computed using Hebbian operations and do not require backpropagation of error signals. Moreover, standard kernel methods could potentially be applied to compute such inner products. We propose that the main reason that recurrent neural networks have not worked well in engineering applications (e.g., speech recognition) is that they implicitly rely on a very simplistic likelihood model. The diffusion network approach proposed here is much richer and may open new avenues for applications of recurrent neural networks. We present some analysis and simulations to support this view. Very encouraging results were obtained on a visual speech recognition task in which neural networks outperformed hidden Markov models.
Modeling Real Objects Using Video See-Through Augmented Reality
Authors: Lee Joohi , Hirota Gentaro , State Andrei
Published: July 2002

This paper presents an interactive “what-you-see-is-what-you-get” (WYSIWYG) method for creating textured 3-D models of real objects using video see-through augmented reality. We use a tracked probe to sample the objects' geometries, and we acquire video images from the head-mounted cameras to capture textures. Our system provides visual feedback during modeling by overlaying the model onto the real object in the user's field of view. This visual feedback makes the modeling process interactive and intuitive.
EX ORIENTE LUXURIA: INDIAN COMMODITIES AND ROMAN EXPERIENCE
Authors: Parker Grant
Published: July 2002

The role of commodities from the Indian Ocean is at the centre of this study of Roman imperial worldviews (c. 1st to 6th century). It begins by surveying the various kinds of objects brought to the Mediterranean from South Asia, e.g. spices and fabrics, and their routes, and then examines the ways in which Romans thought about them, both moralising and more strictly economic. This affords the chance to assess the notion of the exotic in Roman culture. Le rôle des marchandises venant de l'Océan Indien se retrouve au centre de cette étude des visions romaines impériales du monde (1er au 6e siècles). Ce travail commence par une étude générale des objets variés importés à la région méditerranéenne de l'Asie du Sud, par exemple des épices et des tissus, et de leurs itinéraires, et examine par la suite ce que les Romains peuvent en avoir pensé du point de vue moralisant et plus strictement économique. Ceci permet d'évaluer la notion de l'exotisme dans la culture romaine.
"BEHOLD MY SERVANT JEHOIACHIN"
Authors:   Goulder
Published: July 2002

King Jehoiachin's life resembles that implied of Isaiah's Servant, so often a term for the king. He grew up as Crown Prince in Jerusalem, "before Yahweh as a tender plant". It was not he who broke the vassal-treaty: "he had done no violence, neither was any deceit in his mouth". In 597 he was arrested, sentenced and deported: "from oppression and judgement he was taken away". He was almost certainly flogged: "he was wounded . . . by his stripes". Jeremiah despised him: "he was despised and we esteemed him not". He spent 37 years in a Babylonian prison: "cut off from the land of the living . . . [Nebuchadnezzar] appointed his grave with the wicked". He was elevated in 561 by Amel-Marduk, and promoted over other kings: "My servant shall be exalted. Kings shall shut their mouths because of him". This news caused amazement in Jerusalem: "Who hath believed that which we have heard?"
Male and female responses to call playback in the Andean frog Colostethus subpunctatus
Authors: Lüddecke Horst
Published: July 2002

Because Colostethus subpunctatus males tend to aggregate, it is likely that calling neighbours communicate vocally. Males advertise by producing long series of short notes at regular intervals. Note repetition rates may vary individually. To determine whether the vocal response to playback of an individual's own advertisement call depended mainly on his initial note repetition rate or on temperature, I experimented with 49 isolated calling males under field conditions. Two different responses occurred. The response type was independent of initial note repetition rate and ambient temperature. Twenty-six males maintained the basic pattern of the advertisement call, but irrespective of temperature they significantly increased note repetition rate in correlation to the initial rate. Twenty-three males changed their call pattern by grouping 2-3 notes into a bout with much shorter silent intervals between notes. Bout repetition rate was also correlated with the initial note rate, but it was lower. To interpret the role of different call patterns, phonotaxis behaviour of twelve females was studied in two-choice laboratory experiments. Each female had the opportunity to choose four times between the advertisement call with low and high note repetition rate, and four times between the latter and the bout. Females tended to choose the high repetition rate more often than the low rate or the bout. The study provides support that an increase in note repetition rate gives competitive advantage to the caller in attracting a female. Bouts are probably aggressive signals used by a resident to repel intruders from his calling site.
Carbon dioxide influences environmental sex determination in two species of turtles
Authors: Ewert Michael , Phillips John , Etchberger Cory , Nelson Craig
Published: July 2002

Eggs of wild caught Trachemys scripta and Graptemys pseudogeographica kohnii, two emydine turtles known to have temperature-dependent sex determination, were incubated at 28.5°C in boxes aerated with one of four gas mixtures (two in G. p. kohnii). Across all eggs, elevated levels of carbon dioxide significantly feminized sex ratios in both species and also reduced hatching success. When eggs were grouped into clutches, all comparisons between 0% and elevated carbon dioxide showed feminization in the portions of the clutches at elevated carbon dioxide, a statistically significant result for T. scripta. Accumulation of biogenic carbon dioxide from embryonic respiration and other sources is thus likely to affect sex ratios in natural nests under some conditions, perhaps through an effect on some aspects of embryonic pH.
Longevity and sexual size dimorphism of the Pampa de Achala copper lizard Pristidactylus achalensis (Gallardo, 1964)
Authors: Sinsch Ulrich , di Tada Ismael , Martino Adolfo
Published: July 2002

Longevity and sex-specific growth of the neotropical lizard Pristidactylus achalensis was studied from 1993 to 1998 in a population inhabiting the Pampa de Achala, Sierras Grandes de Cordoba, Argentina, at an elevation of 2,000 m. Capture effort concentrated on the territorial adults which were detected while basking. Each of the 149 individuals studied was sexed, morphometrically described and toe-clipped. The second phalanx was used for skeletochronological age estimation and retrospective growth reconstruction, in some voucher specimens additionally the humerus to validate LAG counts in the phalanx cross sections. Longevity was about the same in males (9 LAGs) and females (10 LAGs) but may be even larger in non-territorial individuals. Sexual maturity was usually attained at an age of 3 LAGs, only occasionally one year earlier. With respect to snout-cloaca length, females were always significantly smaller than males of the same age. Bone growth (increase of LAG diameter) revealed that the sexual size dimorphism was related to a significantly lower growth rate of females following hatching. Age and size were correlated (rs = 0.564, n = 149, P << 0.001), but still most of the total size variance remained unexplained by age. Maximum size was approached asymptotically with more than 90% of size increase occuring during the first three years of life: 46.0 ± 1.7 mm (1 LAG), 81.3 ± 5.6 mm (2 LAG), 100.1 ± 0.7 mm (3 LAGs). Territorial individuals rarely were successful to defend a territory more than one activity period, as evidenced by a low recapture probability and a stable between-years age structure of this group.
On the Significance of Nature for the Question of Ethics
Authors: Schmidt Dennis
Published: July 2002

The purpose of this article is to begin to renew the theme of nature as a central, even unavoidable, question for philosophizing today. Furthermore, the argument is made that this question is most productively posed as a question concerning ethical life. Texts by Aristotle, Kant and Höderlin are considered. Attention to Heidegger's concerns with technology also serves to guide the issues here.
Corrosive Effects: Environmental Ethics and the Metaphysics of Acid Mine Drainage
Authors: Frodeman Robert
Published: July 2002

Environmentally we seem to be both the victims and the perpetrators of a type of bait and switch: lured into the discussion by one set of intuitions, our interests become redescribed in terms that are intellectually more respectable. Our deepest concerns with the environment are converted into foreign discourses, as we strain to make the languages of science, economics, and interest group politics express our intuitions. The circumscription of environmental philosophy within environmental ethics is one manifestation of this process of bait and switch. 'Corrosive Effects' critiques this process through a case study of acid mine drainage-water pollution resulting from mining activities. An analysis of acid mine drainage reveals the metaphysical and theological roots of many of our environmental problems.
Consumer Confidence in the Responsible Use of Digital Health Data After the COVID-19 Pandemic
Authors: Gupta Ravi , Sharma Meghana , Mitra Nandita , Cannuscio Carolyn C. , Merchant Raina M. , Asch David A. , Grande David
Published: February 2025

This study compares 2020 and 2022 surveys to identify changes in how respondents view use of their health information by public and private organizations, including by political leaning.