bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced circadian ACTH release in obese premenopausal women: reversal by short-term acipimox treatment
Authors: Kok Petra , Kok Simon W. , Buijs Madelon M. , Westenberg Jos J. M. , Roelfsema Ferdinand , Frölich Marijke , Stokkel Marcel P. M. , Meinders A. Edo , Pijl Hanno
Published: July 2004

Several studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis is exceedingly active in obese individuals. Experimental studies show that circulating free fatty acids (FFAs) promote the secretory activity of the HPA axis and that human obesity is associated with high circulating FFAs. We hypothesized that HPA axis activity is enhanced and that lowering of circulating FFAs by acipimox would reduce spontaneous secretion of the HPA hormonal ensemble in obese humans. To evaluate these hypotheses, diurnal ACTH and cortisol secretion was studied in 11 obese and 9 lean premenopausal women (body mass index: obese 33.5 ± 0.9 vs. lean 21.2 ± 0.6 kg/m2, P < 0.001) in the early follicular stage of their menstrual cycle. Obese women were randomly assigned to treatment with either acipimox (inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double-blind crossover design, starting one day before admission until the end of the blood-sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of plasma ACTH and cortisol concentrations. ACTH and cortisol secretion rates were estimated by multiparameter deconvolution analysis. Daily ACTH secretion was substantially higher in obese than in lean women (7,950 ± 1,212 vs. 2,808 ± 329 ng/24 h, P = 0.002), whereas cortisol was not altered (obese 36,362 ± 5,639 vs. lean 37,187 ± 4,239 nmol/24 h, P = 0.912). Acipimox significantly reduced ACTH secretion in the obese subjects (acipimox 5,850 ± 769 ng/24 h, P = 0.039 vs. placebo), whereas cortisol release did not change (acipimox 33,542 ± 3,436 nmol/24 h, P = 0.484 vs. placebo). In conclusion, spontaneous ACTH secretion is enhanced in obese premenopausal women, whereas cortisol production is normal. Reduction of circulating FFA concentrations by acipimox blunts ACTH release in obese women, which suggests that FFAs are involved in the pathophysiology of this neuroendocrine anomaly.
c-Fos expression in rat brain stem and spinal cord in response to activation of cardiac ischemia-sensitive afferent neurons and electrostimulatory modulation
Authors: Hua Fang , Harrison Theresa , Qin Chao , Reifsteck Angela , Ricketts Brian , Carnel Charles , Williams Carole A.
Published: July 2004

The purpose of this study was to identify central neuronal sites activated by stimulation of cardiac ischemia-sensitive afferent neurons and determine whether electrical stimulation of left vagal afferent fibers modified the pattern of neuronal activation. Fos-like immunoreactivity (Fos-LI) was used as an index of neuronal activation in selected levels of cervical and thoracic spinal cord and brain stem. Adult Sprague-Dawley rats were anesthetized with urethane and underwent intrapericardial infusion of an “inflammatory exudate solution” (IES) containing algogenic substances that are released during ischemia (10 mM adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine) or occlusion of the left anterior descending coronary artery (CoAO) to activate cardiac ischemia-sensitive (nociceptive) afferent fibers. IES and CoAO increased Fos-LI above resting levels in dorsal horns in laminae I–V at C2 and T4 and in the caudal nucleus tractus solitarius. Dorsal rhizotomy virtually eliminated Fos-LI in the spinal cord as well as the brain stem. Neuromodulation of the ischemic signal by electrical stimulation of the central end of the left thoracic vagus excited neurons at the cervical and brain stem level but inhibited neurons at the thoracic spinal cord during IES or CoAO. These results suggest that stimulation of the left thoracic vagus excites descending inhibitory pathways. Inhibition at the thoracic spinal level that suppresses the ischemic (nociceptive) input signal may occur by a short-loop descending pathway via signals from cervical propriospinal circuits and/or a longer-loop descending pathway via signals from the nucleus tractus solitarius.
Mathematical modeling of vascular endothelial layer maintenance: the role of endothelial cell division, progenitor cell homing, and telomere shortening
Authors: Buijs Jorn Op den , Musters Mark , Verrips Theo , Post Jan Andries , Braam Branko , van Riel Natal
Published: July 2004

Maintenance of the endothelial cell (EC) layer of the vessel wall is essential for proper functioning of the vessel and prevention of vascular disorders. Replacement of damaged ECs could occur through division of surrounding ECs. Furthermore, EC progenitor cells (EPCs), derived from the bone marrow and circulating in the bloodstream, can differentiate into ECs. Therefore, these cells might also play a role in maintenance of the endothelial layer in the vascular system. The proliferative potential of both cell types is limited by shortening of telomeric DNA. Accelerated telomere shortening might lead to senescent vascular wall cells and eventually to the inability of the endothelium to maintain a continuous monolayer. The aim of this study was to describe the dynamics of EC damage and repair and telomere shortening by a mathematical model. In the model, ECs were integrated in a two-dimensional structure resembling the endothelium in a large artery. Telomere shortening was described as a stochastic process with oxidative damage as the main cause of attrition. Simulating the model illustrated that increased cellular turnover or elevated levels of oxidative stress could lead to critical telomere shortening and senescence at an age of 65 yr. The model predicted that under those conditions the EC layer could display defects, which could initiate severe vascular wall damage in reality. Furthermore, simulations showed that 5% progenitor cell homing/yr can significantly delay the EC layer defects. This stresses the potential importance of EPC number and function to the maintenance of vascular wall integrity during the human life span.
Dissociation of renal TGF-β and hypertrophy in female rats with diabetes mellitus
Authors: Lane Pascale H. , Sun Jianhong , Devish Kay , Langer William J.
Published: July 2004

Prepubertal onset of diabetes mellitus (DM) in male rats delays diabetic renal hypertrophy and suppresses renal transforming growth factor-β (TGF-β) compared with onset in adults. Because there are sex differences in normal and pathological renal growth, we performed similar experiments in female rats and examined the effects of prior ovariectomy. As in male rats, adult onset of DM increased renal weight ∼35%, total renal TGF-β ∼35%, and mRNA for TGF-β inducible gene H3 (βIG-H3) ∼200%. TGF-β levels did not increase with DM in prepubertal animals, but renal weight increased ∼40%, similar to the enlargement seen in adults. In nondiabetic rats, ovariectomy suppressed renal TGF-β levels by 25–50% in both age groups, but βIG-H3 was stable in younger animals and increased by ∼200% in older animals after ovariectomy. Ovariectomy increased kidney weight ∼10% in both age groups. DM further increased kidney weight by an additional 40% after ovariectomy with an ∼150% increase in βIG-H3, even though TGF-β levels were not significantly increased. Prepubertal (∼99% lower), diabetic (∼50% lower), and ovariectomized rats (∼90% lower) all tended toward lower estradiol levels than intact adults, although not all differences were statistically significant. Both prepubertal onset and ovariectomy suppress TGF-β in the kidneys of female rats with DM compared with adult-onset animals, but these states have no effect on renal enlargement. Production of the extracellular matrix component βIG-H3 is dissociated from TGF-β under these conditions. These observations may help explain some of the sex differences demonstrated in progressive kidney diseases, including DM.
Liver X receptor-α mediates cholesterol efflux in glomerular mesangial cells
Authors: Wu Jing , Zhang Yahua , Wang Nanping , Davis Linda , Yang Guangrui , Wang Xian , Zhu Yi , Breyer Matthew D. , Guan Youfei
Published: July 2004

Lipid-mediated injury plays an important role in the pathogenesis of many renal diseases including diabetic nephropathy. Liver X receptor-α (LXRα) is an intracellular sterol sensor that regulates expression of genes controlling cholesterol absorption, excretion, catabolism, and cellular efflux. The present study was aimed at examining the role of LXRα in cholesterol metabolism in glomerular mesangial cells. A 1,561-bp fragment of full-length rabbit LXR cDNA was cloned. The deduced protein sequence exhibited 92.4 and 89.2% identity to human and mouse LXRα, respectively. Tissue distribution studies showed that rabbit LXRα was expressed in the liver, spleen, and kidney. In situ hybridization and RT-PCR assays further indicated that LXRα mRNA was widely expressed in the kidney and present in every nephron segment including the glomeruli. To determine intrarenal regulation of LXRα, rabbits were treated with thiazolidinedione (TZD) peroxisome proliferator-activated receptor-γ (PPARγ) agonists, which have been previously shown to enhance LXRα expression via PPARγ and increase cholesterol efflux in macrophages. The results showed that glomerular LXRα expression was markedly induced by TZDs. In cultured rabbit mesangial cells, LXRα mRNA and protein were detected by RT-PCR and immunoblotting. Treatment of mesangial cells with a specific LXRα agonist, TO-901317, significantly increased basal and apolipoprotein AI-mediated cholesterol efflux and markedly enhanced the promoter activity of an LXRα target gene, ATP-binding cassette transporter A1 (ABCA1). In conclusion, LXRα is expressed in renal glomeruli and functionally present in mesangial cells where its activation mediates cholesterol efflux via ABCA1. These data suggest that LXRα may be a potential therapeutic target for treating lipid-related renal glomerular disease.
Determinants of basal nitric oxide concentration in the renal medullary microcirculation
Authors: Zhang Wensheng , Pibulsonggram Tosapol , Edwards Aurélie
Published: July 2004

In this study, we modeled the production, transport, and consumption of nitric oxide (NO) in the renal medullary microcirculation under basal conditions. To yield agreement with reported NO concentrations of ∼60–140 nM in medullary tissues (Zou AP and Cowley AW Jr. Hypertension 29: 194–198, 1997; Am J Physiol Regul Integr Comp Physiol 279: R769–R777, 2000) and 3 nM in plasma (Stamler JS, Jaraki O, Osborne J, Simon DI, Keaney J, Vita J, Singel D, Valeri CR, and Loscalzo J. Proc Natl Acad Sci USA 89: 7674–7677, 1992), the permeabilities of red blood cells (RBCs), vascular walls, and pericytes to NO are all predicted to lie between 0.01 and 0.1 cm/s, and the NO production rate by vasa recta endothelium is estimated to be on the order of 10−14μmol·μm−2·s−1. Our results suggest that the concentration of NO in RBCs, which is essentially controlled by the kinetics of NO scavenging by hemoglobin, is ∼0.01 nM, that is, 103times lower than that in plasma, pericytes, and interstitium. Because the basal concentration of NO in pericytes is on the order of 10 nM, it may be too low to active guanylate cyclase, i.e., to induce vasorelaxation. Our simulations also indicate that basal superoxide concentrations may be too low to affect medullary NO levels but that, under pathological conditions, superoxide may be a very significant scavenger of NO. We also found that although oxygen is a negligible NO scavenger, medullary hypoxia may significantly enhance NO concentration gradients along the corticomedullary axis.
Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp
Authors: Nissant Antoine , Lourdel Stéphane , Baillet Sophie , Paulais Marc , Marvao Pedro , Teulon Jacques , Imbert-Teboul Martine
Published: July 2004

The distal convoluted tubule (DCT) is a heterogeneous segment subdivided into early (DCT1) and late (DCT2) parts, depending on the distribution of various transport systems. We do not have an exhaustive picture of the Cl−channels on the basolateral side: the presence of ClC-K2 channels is generally accepted, whereas that of ClC-K1 remains controversial. We used here single-cell RT-PCR and patch clamp to probe Cl−channel heterogeneity in microdissected mouse DCT at the molecular and functional levels. Our findings show that 63% of the DCT cells express ClC-K2 mRNA, either alone (type 1 cells: 47 and 23% in DCT1 and DCT2, respectively), or combined with ClC-K1, mostly in DCT2 (type 2 cells: 33%), but 37% of DCT1 and DCT2 cells do not express any ClC-K. Patch-clamp experiments revealed that a Cl−channel, with 9-pS conductance and Cl−> NO3−= Br−anion selectivity sequence, is present in the DCT1 and DCT2 basolateral membranes (87 and 71% of the patches, respectively). This dominant channel is likely to be ClC-K2 in type 1 cells. In type 2 cells, it could be ClC-K2 and/or ClC-K1 homodimers, but also ClC-K1/ClC-K2 heterodimers, or a mixture of all combinations. A second, distinct Cl−channel (13% of DCT1 patches, 29% of DCT2 patches) also displayed 9-pS conductance but had a completely different anion selectivity (I−> NO3−> Br−> Cl−), which was not compatible with that of the ClC-Ks. This indicates that a Cl−channel that is unlikely to belong to the ClC family may also be involved in Cl−absorption in the DCT2.
Spontaneous Waves in the Dentate Gyrus of Slices From the Ventral Hippocampus
Authors: Colgin Laura Lee , Kubota Don , Brucher Fernando A. , Jia Yousheng , Branyan Erin , Gall Christine M. , Lynch Gary
Published: July 2004

Spontaneous negative-going potentials occurring at an average frequency of 0.7 Hz were recorded from the dentate gyrus of slices prepared from the temporal hippocampus of young adult rats. These events (here termed “dentate waves”) in several respects resembled the dentate spikes described for freely moving rats during immobile behaviors and slow-wave sleep. Action potentials were observed on the descending portion of the in vitro waves and, as expected from this, whole cell recordings established that the waves were composed of depolarizing currents. Dentate waves appeared to be locally generated within the granule cell layer and were greatly reduced by antagonists of AMPA-type glutamate receptors or by lesions to the entorhinal cortex. Simultaneous recordings indicated that the waves were often synchronized in the inner and outer blades of the dentate gyrus. Knife cuts through the perforant path and the commissural/associational system did not eliminate synchronization, leaving electrotonic propagation via gap junctions as its probable cause. In accord with this, cuts that separated the two blades of the dentate eliminated synchronization between them, and a compound that inhibits gap junctions reduced wave activity. Dentate waves were regularly accompanied by sharp waves in field CA3 and were reduced in size by the acetylcholinesterase inhibitor, physostigmine. It is hypothesized that dentate waves occur when spontaneous glutamate release from dentate afferents produces action potentials in neighboring granule cells that then summate electrotonically into a population event; once initiated, the waves propagate, again electrotonically, and thereby engage a significant portion of the granule cell population.
Anorexia and Serum Leptin Levels in Hemodialysis Patients
Authors: Bossola Maurizio , Muscaritoli Maurizio , Valenza Venanzio , Panocchia Nicola , Tazza Luigi , Cascino Antonia , Laviano Alessandro , Liberatori Massimo , Lodovica Moussier Maria , Rossi Fanelli Filippo , Luciani Giovanna
Published: July 2004

Background and Aims: Hyperleptinemia is a common feature in hemodialysis (HD) patients. However, the role of increased serum leptin levels in the pathogenesis of HD-related anorexia is still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is causally implicated in the pathogenesis of HD-related anorexia. Methods: We measured the serum leptin levels and the serum leptin/body mass index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. HD patients were subdivided into anorexic (14/49, 28.5%) and non-anorexic (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms. Results: Calorie (kcal/kg/day) and protein (g/ kg/day) intakes were significantly lower in anorexic than in non-anorexic patients (20.1 ± 1.1 vs. 27.9 ± 1.3, p = 0.004, and 0.82 ± 0.05 vs. 1.19 ± 0.05, p = 0.001, respectively). Accordingly, serum albumin, total lymphocyte count, mid-arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in anorexic patients. The serum leptin concentration (ng/ml) was significantly higher in HD patients than in controls, in males (15.33 ± 3.4 vs. 3.7 ± 0.3, p = 0.003) and in females (42.3 ± 7.2 vs. 10.5 ± 1.3, p = 0.03). Similarly, serum leptin/BMI ratio was significantly higher in HD patients than in controls, in males (0.56 ± 0.1 vs. 0.16 ± 0.02, p = 0.0028) and in females (1.8 ± 0.2 vs. 0.4 ± 0.04, p < 0.0001). However, serum leptin levels were similar in anorexic and in non-anorexic patients, in males (15.3 ± 5.6 vs. 16.9 ± 4.2, p = 0.85) and in females (46.6 ± 12.9 vs. 47.4 ± 9.4, p = 0.96). No differences were observed between the 2 groups in the serum leptin/BMI ratio, in males (0.59 ± 0.2 vs. 0.58 ± 0.14, p = 0.92) and in females (1.5 ± 0.4 vs. 1.8 ± 0.3, p = 0.94). Similarly, no statistically significant differences in terms of serum leptin levels and leptin/BMI ratio were observed between patients with dietary energy intake of <30 or ≧30 kcal/kg/day and between those with a dietary protein intake of <1.2 or ≧1.2 g/kg/day. No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement. Conclusion: The present results indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia.
Erdosteine Improves Oxidative Damage in a Rat Model of Renal Ischemia-Reperfusion Injury
Authors: Gurel A. , Armutcu F. , Cihan A. , Numanoglu K.V. , Unalacak M.
Published: July 2004

The aim of the present study was to determine the effects of erdosteine, a new antioxidant and anti-inflammatory agent, on lipid peroxidation, neutrophil infiltration, and antioxidant enzyme activities in a rat model of renal ischemia-reperfusion (I/R) injury. Twenty-eight rats were divided into three groups: sham operation, I/R, and I/R plus erdosteine groups. After the experimental procedure, rats were sacrificed and kidneys were removed and prepared for malondialdehyde (MDA) levels, myeloperoxidase (MPO), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. MDA level, MPO and XO activities were significantly increased in the I/R group. On the other hand, SOD and CAT activities were found to be decreased in the I/R group compared to the sham group. Pretreatment with erdosteine significantly diminished tissue MDA level, MPO and XO activities. Our data support a role for erdosteine in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration and XO activity.
Exogenous and Endogenous Nitric Oxide Donors Improve Post-Ischemic Tissue Oxygenation in Early Pancreatic Ischemia/Reperfusion Injury in the Rat
Authors: Obermaier R. , von Dobschuetz E. , Benthues A. , Ansorge N. , Schareck W. , Hopt U.T. , Benz S.
Published: July 2004

Introduction: In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of nitric oxide (NO) is not completely understood. Using a rat model of normothermic in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic tissue oxygenation and tissue damage was investigated. Methods: IR was induced by 2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without ischemia served as controls. Tissue oxygenation (pO2ti) was monitored using a pO2-sensitive Clark-type electrode. Histological investigation was performed following a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). Plasma lipase was another marker of organ damage. Results: The administration of L-arginine and sodium nitroprusside caused a significant amelioration of the decrease in pO2ti after reperfusion compared to IR animals (p < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05). After reperfusion, plasma lipase in the L-arginine-treated animals was significantly lower compared to IR and sodium nitroprusside (p < 0.05). Conclusions: The administration of both endogenous and exogenous NO donors is protective in IRI of the rat pancreas which can be seen by an improvement in post-ischemic tissue oxygenation which indicates better nutritive tissue perfusion, amelioration of the histological tissue injury and, in L-arginine animals, lower lipase levels. NO donors could be useful in the prevention and reduction of the pancreatic IRI.
Effects of Obstructive Jaundice on the Peripheral Nerve: An Ultrastructural Study in Rats
Authors: Can B. , Saray A. , Caglikulekçi M. , Saran Y.
Published: July 2004

Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated with peripheral neuropathy in several clinical studies. The study evaluated the effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group, jaundice was created by ligation of common bile duct in Wistar-Albino rats. In the sham-operated control group the same procedure was performed without ligation of the bile duct. On day 7, all rats were re-operated and sciatic nerves were explored to harvest 2-cm-long nerve segments for quantitative and qualitative histopathological analysis by light and electron microscopy. Bilirubin was measured on serum samples. Bilirubin levels were significantly higher in jaundiced rats compared with that of controls (8.46 ± 0.45 vs. 0.80 ± 0.14 mmol/l, means ± SD, p < 0.01). Control nerves did not show anything other than the normal histology. In the OJ group, degenerative changes such as irregularities, thinning, ruffling and invaginations, irregularshaped bodies, vacuolizations and focal segmental demyelination were observed in the myelin sheath. Myelin clusters were noted in the axoplasm. A varying degree of swelling was noted in the nucleus and cytoplasm of the Schwann cells. Morphometric analysis of specimens obtained from sciatic nerves showed that myelin injury (370.9 ± 51.3 vs. 11.6 ± 0.5 axons), axonal edema (142.1 ± 24.2 vs. 10.6 ± 0.5 edematous axons) and Schwann cell degeneration (50.3 ± 11.6 vs. 3.2 ± 0.2 Schwann cells) was significantly higher in the jaundiced rats than in the control group (p < 0.01). The ultrastructural alterations spotted in the rat peripheral nerve were attributed to hyperbilirubinemia and increased concentrations of several neurotoxic substances released from the Kupffer cells in OJ. Neuropathy in jaundiced patients seems to result from accompanying degenerative changes in the peripheral nervous system. However, the exact nature and initiating factors of this nerve injury remains to be unveiled.
Effects of Hypericum Extract (LI160) on the Change of Auditory Evoked Potentials by Cortisol Administration
Authors: Murck Harald , Uhr Manfred , Schaffler Klaus , Seibel Klaus
Published: July 2004

Target symptoms treated with Hypericum extract, i.e. somatisation, fatigue and depression could be related to an increased activity of glucocorticoids in the brain. One potential mechanism is the increased permeability of the blood-brain barrier for glucocorticoids. Hypericum extract LI160 reduces intracerebral glucocorticoid concentration possibly by its action to induce the expression of the transport protein P-glycoprotein (P-gp). To test this hypothesis directly, we performed a randomised double-blind crossover study to examine the effect of intravenously administered cortisol on auditory evoked potentials (AEPs) and salivary cortisol concentration. Nineteen healthy subjects were treated for 2 weeks with 300 mg LI160 twice a day or placebo. On the 14th day, AEPs were recorded every 30 min, at times –60, –30 and 0 min before the start of the infusion and at +30, +60 and +90 min after starting the infusion. The rate of infusion was 20 mg cortisol/h. No changes in the AEP, especially the N1-P2 component, could be observed under cortisol infusion and consequently no modification with the treatment of Hypericum extract. The salivary concentration of cortisol under cortisol infusion was slightly but significantly decreased in the Hypericum condition compared to placebo. The results of the present study are therefore inconclusive with respect to the influence of LI160 treatment on the expected cortisol-induced AEP changes, but support the concept of an action of Hypericum on P-gp function by the observed changes in salivary cortisol.
PECAM-1 Interacts With Nitric Oxide Synthase in Human Endothelial Cells
Authors: Dusserre N. , L’Heureux N. , Bell K.S. , Stevens H.Y. , Yeh J. , Otte L.A. , Loufrani L. , Frangos J.A.
Published: July 2004

Objective—

We have previously shown that fluid shear stress (FSS) triggers endothelial nitric oxide synthase (eNOS) activity in endothelial cells and that the mechanotransduction mechanisms responsible for activation discriminate between rapid changes in FSS and FSS per se. We hypothesized that the particular sublocalization of eNOS at the cell–cell junction would render it responsive to activation by FSS temporal gradients.

Methods and Results—

In human umbilical vein endothelial cells (HUVECs), immunofluorescence revealed strong eNOS membrane staining at the cell–cell junction colocalizing with platelet/endothelial cell adhesion molecule-1 (PECAM-1). In PECAM-1 −/− mouse aorta, eNOS junctional localization seen in the wild type was absent. Similarly, junctional staining was lost in wild-type aorta near intercostal artery branches. eNOS/PECAM-1 association in HUVECs was confirmed by coimmunoprecipitation. When HUVECs were subjected to a 0.5s impulse of 12 dynes/cm
2
, a transient disruption of the eNOS/PECAM-1 complex was observed, accompanied by an increase in eNOS activity (cGMP production). Ramped flow did not trigger complex dissociation or an increase in cGMP production. In a cell-free system, a direct inhibition of eNOS activity by PECAM-1 is shown.

Conclusions—

These results suggest that eNOS is complexed with PECAM-1 at the cell–cell junction and is likely involved in the modulation of eNOS activity by FSS temporal gradients but not by FSS itself.
Mild to Moderate Atheromatous Disease of the Thoracic Aorta and New Ischemic Brain Lesions After Conventional Coronary Artery Bypass Graft Surgery
Authors: Djaiani George , Fedorko Ludwik , Borger Michael , Mikulis David , Carroll Jo , Cheng Davy , Karkouti Keyvan , Beattie Scott , Karski Jacek
Published: July 2004

Background and Purpose—

The presence of new ischemic brain infarcts, detected by diffusion-weighted magnetic resonance imaging (DW-MRI), have been reported in considerable number of patients after cardiac surgery. We sought to determine the role of proximal thoracic aortic atheroma in predicting embolic events and new ischemic brain lesions in patients undergoing conventional coronary revascularization surgery.

Methods—

Transesophageal echocardiography and epiaortic scanning was performed to assess the severity of aortic atherosclerosis in the ascending aorta and the aortic arch. Patients were allocated to either low-risk group, (intimal thickness ≤2mm), or high-risk group (intimal thickness >2mm). Transcranial Doppler was used to monitor the middle cerebral artery. DW-MRI was performed 3–7 days after surgery. The NEECHAM Confusion Scale was used for assessment and monitoring patient consciousness level.

Results—

Patients in the high-risk group were considerably older; 71±6 (n=38) versus 67±6 (n=72) years,
P
=0.004 and were more likely to have impaired left ventricular function. Confusion was present in 6 (16%) patients in the high-risk group and 5 (7%) patients in the low-risk group. Patients in the high-risk group had a three-fold increase in median embolic count, 223.5 versus 70.0,
P
=0.0003. DW-MRI detected brain lesions were only present in patients from high-risk group, 61.5 versus 0%,
P
<0.0001. There was significant correlation between the NEECHAM scores and embolic count in the high-risk group; r=0.63,
P
<0.001.

Conclusions—

The findings of this investigation suggest that mild to moderate atheromatous disease of the ascending aorta and the aortic arch (intimal thickness >2mm) is a major contributor to ischemic brain injury after cardiac surgery.
The 3-D Prefrontal Cortex: Hemispheric Asymmetries in Prefrontal Activity and Their Relation to Memory Retrieval Processes
Authors: Ranganath Charan
Published: July 2004

Neuroimaging results have raised interest in characterizing hemispheric asymmetries in prefrontal activity during different types of memory retrieval tasks. In this issue, Dobbins et al. and Mitchell et al. report results suggesting that the two hemispheres of the prefrontal cortex may indeed make different contributions to memory retrieval. Here, I discuss these findings within the context of studies characterizing more general processing differences between the cerebral hemispheres and studies characterizing prefrontal organization along the dorsal– ventral and anterior–posterior dimensions.
Neural Correlates for the Suppression of Habitual Behavior: A Functional MRI Study
Authors: Matsubara Miwa , Yamaguchi Shuhei , Xu Jiang , Kobayashi Shotai
Published: July 2004

It has been suggested that inhibitory executive control of behavior is directed by the frontal lobes. We used functional magnetic resonance imaging to explore the brain regions that are involved in the inhibition of habitual manual responses. Fifteen right-handed subjects performed the rock–scissors– paper game against computer-simulated pictures of hands during the scanning procedure. The subjects were required to win, lose, or draw against the presented picture in a separate block. We considered that the situation in which subjects intentionally lost the game required the suppression of habitual behavior, because it is natural behavior for people to attempt to win the game. Compared with the WIN and DRAW conditions, the left premotor and sensorimotor areas were activated for both hand sessions with a positive correlation with error rates. Importantly, the LOSE condition in the case of the right hand yielded brain activation exclusively in the anterior part of the left inferior frontal gyrus, the activity which showed a negative correlation with error rates. Overall brain activations were predominant in the left hemisphere, irrespective of the hand used for the response. The results suggest that the anterior part of the left inferior frontal gyrus plays a critical role in the inhibition of habitual manual behavior, and that the left hemisphere is dominant for the selection of well-learned manual behavior.
Multisensory Interaction in Saccadic Reaction Time: A Time-Window-of-Integration Model
Authors: Colonius Hans , Diederich Adele
Published: July 2004

Saccadic reaction time to visual targets tends to be faster when stimuli from another modality (in particular, audition and touch) are presented in close temporal or spatial proximity even when subjects are instructed to ignore the accessory input (focused attention task). Multisensory interaction effects measured in neural structures involved in saccade generation (in particular, the superior colliculus) have demonstrated a similar spatio-temporal dependence. Neural network models of multisensory spatial integration have been shown to generate convergence of the visual, auditory, and tactile reference frames and the sensorimotor coordinate transformations necessary for coordinated head and eye movements. However, because these models do not capture the temporal coincidences critical for multisensory integration to occur, they cannot easily predict multisensory effects observed in behavioral data such as saccadic reaction times. This article proposes a quantitative stochastic framework, the time-window-of-integration model, to account for the temporal rules of multisensory integration. Saccadic responses collected from a visual–tactile focused attention task are shown to be consistent with the time-window-of-integration model predictions.
A Role for Cortical Crosstalk in the Binding Problem: Stimulus-driven Correlations that Link Color, Form, and Motion
Authors: Billock Vincent A. , Tsou Brian H.
Published: July 2004

The putative independence of cortical mechanisms for color, form, and motion raises the binding problem—how is neural activity coordinated to create unified and correctly segmented percepts? Binding could be guided by stimulus-driven correlations between mechanisms, but the nature of these correlations is largely unexplored and no one has (intentionally) studied effects on binding if this joint information is compromised. Here, we develop a theoretical framework which: (1) describes crosstalk-generated correlations between cortical mechanisms for color, achromatic form, and motion, which arise from retinogeniculate encoding; (2) shows how these correlations can facilitate synchronization, segmentation, and binding; (3) provides a basis for understanding perceptual oddities and binding failures that occur for equiluminant and stabilized images. These ideas can be tested by measuring both perceptual events and neural activity while achromatic border contrast or stabilized image velocity is manipulated.
Neural Correlates of Auditory Repetition Priming: Reduced fMRI Activation in the Auditory Cortex
Authors: Bergerbest Dafna , Ghahremani Dara G. , Gabrieli John D. E.
Published: July 2004

Repetition priming refers to enhanced or biased performance with repeatedly presented stimuli. Modality-specific perceptual repetition priming has been demonstrated behaviorally for both visually and auditorily presented stimuli. In functional neuroimaging studies, repetition of visual stimuli has resulted in reduced activation in the visual cortex, as well as in multimodal frontal and temporal regions. The reductions in sensory cortices are thought to reflect plasticity in modality-specific neocortex. Unexpectedly, repetition of auditory stimuli has resulted in reduced activation in multimodal and visual regions, but not in the auditory temporal lobe cortex. This finding puts the coupling of perceptual priming and modality-specific cortical plasticity into question. Here, functional magnetic resonance imaging was used with environmental sounds to reexamine whether auditory priming is associated with reduced activation in the auditory cortex. Participants heard environmental sounds (e.g., animals, machines, musical instruments, etc.) in blocks, alternating between initial and repeated presentations, and decided whether or not each sound was produced by an animal. Repeated versus initial presentations of sounds resulted in repetition priming (faster responses) and reduced activation in the right superior temporal gyrus, bilateral superior temporal sulci, and right inferior prefrontal cortex. The magnitude of behavioral priming correlated positively with reduced activation in these regions. This indicates that priming for environmental sounds is associated with modification of neural activation in modality-specific auditory cortex, as well as in multimodal areas.
A Tale of Two Times: Preaching in the Latter Age of the Dharma
Authors: Hubbard Jamie
Published: July 2004

Sharing a cyclical cosmogony with other Indian worldviews, Buddhism is ordinarily thought to be unconcerned with specific historical events, looking instead towards the individual transcendence of temporal becoming as the goal of religious practice. One counterpoint to this prevailing attitude is the tradition of the decline of the dharma, premised upon the historical uniqueness or specificity of Śākyamuni's teachings and an attendant eschatological consciousness of temporal distance from the time of the teacher and his teachings. Interestingly, the Lotus Sutra presents both a transcendent and historically unique interpretation of Śākyamuni's lifetime. Nichiren, among others, attached importance to the historical specificity of Śākyamuni and his teachings, and hence understood the Lotus Sutra to demand attention to the preaching or evangelical spread of the true teachings.
Pop Goes the Arab World: Popular Music, Gender, Politics, and Transnationalism in the Arab World
Authors: Choucair Julia , Mikdashi Maya , Agha Jehan , Abdel-Nabi Shereen
Published: July 2004

Assumptions are often made as to the static nature of contemporary Arab politics and societies. Authors, scholars and commentators look for sociopolitical dynamism in the arenas they are used to: newspapers, television and parliament/congress, to name but a few. When they do not see or hear these debates taking place in the formal institutions that they are familiar with, they are quick to assume that these reassessments are simply not occurring. Nothing could be further from the truth. The Arab world is debating itself on matters of politics, identity and gender roles, to name but a few subjects. The debate space that is being utilized, however, is easily unnoticeable to those who are not adept at finding these forums and are instead used to being presented with them. When public space is limited, any opening will be used to the utmost. The ways in which the Arab world imagines and recreates itself is often through art. Satellite television and the strengthening of transnational media has helped the populations of this widely defined nation come into contact with each other in a realm outside of state control. Artists can become peoples' most important and trusted politicians. A medium readily accessible for consumption and easy to understand, popular music addresses important themes that speak to a collective audience and tie it together as a community. This paper seeks to examine the political, identity and gender debates that are currently occurring within the realm of popular music.
Forgotten Women: Prostitution and Social Representations of Immigrants with Muslim Origin
Authors: Treppete Mariangela , Bertani Michele
Published: July 2004

This paper is an introduction containing general reflections on on-going research where the aim is to analyze how in Italy the prostitution of persons coming from countries with a Muslim religion or culture is organized. Given the newness of the subject, presenting a description of the work carried out so far seemed like a suitable starting point with this paper; only after all research has been completed will it be possible to attempt a more significant sociologically closer linked reflection.
TWO MASTERS OF EGYPTIAN 'AMMIYYA POETRY
Authors: Radwan Noha
Published: July 2004

Although verse forms in the colloquial dialects of Arabic have been attested at least since the twelfth century, it is still fair to say that the advent of shi'r al-'ammiyya in the late 1950s was an unprecedented movement in Arabic poetry. Until then, colloquial Arabic was the register of folkloric and 'low' arts produced by and for the uneducated masses. Even when educated literati chose to write in the colloquial, their choice was always motivated by such limited purposes as the wish to satirize the literary establishment and its 'elite' literature or to reach a mass audience. Didactic and politically charged poetry reached its height in the works of Bayram al-Tunisi, who denounced fusha as elitist and championed 'ammiyya for its accessibility to the Egyptian masses. In contrast, the poets of shi'r al-ammiyya believe that both the standard fush&a and the colloquial 'ammiyya are fit for poetic expression. Their poetry is the product of the cross-fertilization of the literary and the oral traditions. It is a poetry that can only be appreciated in the context of the goals and accomplishments of the modernist movement in Arabic poetry. This article provides a reading of a poem by each of the two early masters of shi'r al-'ammiyya, Fu'ad Haddad and Salah Jahin, with the purpose of illustrating the nature of the genre, its distinctiveness from previous forms of colloquial poetry, and the wide and diverse spectrum of modern poetic expression in Egyptian colloquial.
THE HISTORIC ENCOUNTER BETWEEN AL-MUTANABBI AND AL-HATIMI ITS CONTRIBUTION TO THE DISCOURSE ON GHULUWW (HYPERBOLE) IN ARABIC LITERARY THEORY
Authors: Sanni Amidu
Published: July 2004

Literary seances historically served as platforms for discussions and intellectual competitions. The discussion arising from the encounter between al-Mutanabbi (d. 965) and al-Hatimi (d. 998) concerning hyperstatement, metaphor, and aesthetic emphasis in poetic expression betrays a familiar but not an uncommon hiatus in perception and conceptualization between the Arab poet and his evaluator in the literary tradition. This study attempts to chart the course of development of a coherent theory on hyperbole from the earliest period of theoretical speculation in Arabic until the emergence of a formal theory. The study uses the text and the subtext of the recorded encounter between the two protagonists as contained in al-Hatimi's work.
Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait
Authors: Ayi Kodjo , Turrini Franco , Piga Antonio , Arese Paolo
Published: July 2004

High frequency of erythrocyte (red blood cell [RBC]) genetic disorders such as sickle cell trait, thalassemia trait, homozygous hemoglobin C (Hb-C), and glucose-6-phosphate dehydrogenase (G6PD) deficiency in regions with high incidence of Plasmodium falciparum malaria and case-control studies support the protective role of those conditions. Protection has been attributed to defective parasite growth or to enhanced removal of the parasitized RBCs. We suggested enhanced phagocytosis of rings, the early intraerythrocytic form of the parasite, as an alternative explanation for protection in G6PD deficiency. We show here that P falciparum developed similarly in normal RBCs and in sickle trait, beta- and alpha-thalassemia trait, and HbH RBCs. We also show that membrane-bound hemichromes, autologous immunoglobulin G (IgG) and complement C3c fragments, aggregated band 3, and phagocytosis by human monocytes were remarkably higher in rings developing in all mutant RBCs considered except alpha-thalassemia trait. Phagocytosis of ring-parasitized mutant RBCs was predominantly complement mediated and very similar to phagocytosis of senescent or damaged normal RBCs. Trophozoite-parasitized normal and mutant RBCs were phagocytosed similarly in all conditions examined. Enhanced phagocytosis of ring-parasitized mutant RBCs may represent the common mechanism for malaria protection in nonimmune individuals affected by widespread RBC mutations, while individuals with alpha-thalassemia trait are likely protected by a different mechanism. (Blood. 2004;104:3364-3371)
Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease
Authors: Tanaka Masashi , Nakae Susumu , Terry Raya D. , Mokhtari Golnaz K. , Gunawan Feny , Balsam Leora B. , Kaneda Hideaki , Kofidis Theo , Tsao Philip S. , Robbins Robert C.
Published: July 2004

After cardiac transplantation, graft damage occurs secondary to ischemia-reperfusion injury and acute rejection. This damage ultimately leads to the development of graft coronary artery disease (GCAD), which limits long-term graft survival. Apoptosis is directly involved in graft injury, contributing to the development of GCAD. To assess the role of the antiapoptotic factor Bcl-2 in the process of GCAD, we transplanted hearts from FVB transgenic mice overexpressing human Bcl-2 under the control of α-myosin heavy chain promoter into allogenic C57BL/6 mice. Bcl-2 overexpression led to reduced cytochrome c–mediated caspase-9–dependent cardiomyocyte apoptosis and local inflammation (neutrophil infiltration and proinflammatory cytokine production) in cardiac allografts during ischemia-reperfusion injury and also led to reduced immune responses (inflammatory cell infiltration, production of TH1 cytokines and chemokines, and expression of adhesion molecules) during acute and chronic rejection without affecting host CD4+ and CD8+ cell responses in the spleen. Thus, local Bcl-2 expression directly contributes to the modulation of local immune responses in allograft rejection, resulting in attenuated GCAD. In conclusion, our findings suggest that the modulation of Bcl-2 expression by pharmacologic up-regulation or gene transfer may be of clinical benefit in the short- and long-term function of cardiac allografts.
Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation
Authors: Chou Janet , Mackman Nigel , Merrill-Skoloff Glenn , Pedersen Brian , Furie Barbara C. , Furie Bruce
Published: July 2004

Tissue factor (TF) is expressed on nonvascular cells and cells within the vessel wall and circulates in blood associated with microparticles. Although blood-borne TF accumulates into the developing thrombus during thrombus formation, the contribution of blood-borne TF and vessel wall TF to thrombin generation in vivo following vessel injury is unknown. To determine the source and role of blood-borne microparticle TF, we studied arterial thrombus formation in a living mouse using intravital microscopy. Platelet, TF, and fibrin accumulation in the developing thrombus was compared in wild-type and low TF mice. Compared to wild-type mice, low TF mice formed very small platelet thrombi lacking TF or fibrin. Wild-type and low TF mice received transplants of bone marrow from wild-type and low TF mice. Arterial thrombi in low TF bone marrow/wild-type chimeric mice had decreased size and decreased TF and fibrin levels. Arterial thrombi in wild-type bone marrow/low TF chimeric mice showed decreased platelet thrombus size but normal TF and fibrin levels. This demonstrates that blood-borne TF associated with hematopoietic cell-derived microparticles contributes to thrombus propagation.
Hairy cell leukemia: at the crossroad of somatic mutation and isotype switch
Authors: Forconi Francesco , Sahota Surinder S. , Raspadori Donatella , Ippoliti Micaela , Babbage Gavin , Lauria Francesco , Stevenson Freda K.
Published: July 2004

Hairy cell leukemia (HCL) commonly expresses multiple immunoglobulin isotypes, a feature rare in other B-cell malignancies or in normal B cells. In HCL, there is no phenotypic evidence for subpopulations, and single cells from one previous case contained transcripts for several isotypes. This raises the questions of the differentiation status of the cell of origin and of posttransformation events. We have investigated 9 cases, all expressing multiple immunoglobulin isotypes. Multiple tumor-derived variable-(diversity)-joining-constant μ δ, γ, α (V(D)J-Cμ, δ, γ, α) transcripts were confirmed in single cells of a further case. All cases were negative for germinal center (GC)-associated markers CD27 and CD38. Seven of 9 cases had mutated VH genes, with low levels of intraclonal heterogeneity, but 2 of 9 were unmutated, indicative of pre-GC origin. Eight of 9 cases expressed activation-induced cytidine deaminase (AID), a molecule essential for somatic mutation and isotype switch. All cases expressed germ line heavy-chain I exon (IH)-CH transcripts which paralleled surface immunoglobulin (sIg) isotype. Significantly, no circle transcripts indicative of deletional recombination of switched isotypes were detectable in 9 of 9 cases. These data indicate heterogeneity in the cell of origin in terms of mutational status, but reveal common features of AID expression and isotype-switching events occurring prior to deletional recombination. Both mutational and switching events may be influenced by environmental factors at extrafollicular sites. (Blood. 2004;104:3312-3317)