bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic AMP Cascade Mediates the Inhibitory Odor Response of Isolated Toad Olfactory Receptor Neurons
Authors: Madrid Rodolfo , Delgado Ricardo , Bacigalupo Juan
Published: April 2005

Odor stimulation may excite or inhibit olfactory receptor neurons (ORNs). It is well established that the excitatory response involves a cyclic AMP (cAMP) transduction mechanism that activates a nonselective cationic cyclic nucleotide-gated (CNG) conductance, accompanied by the activation of a Ca2+-dependent Cl−conductance, both causing a depolarizing receptor potential. In contrast, odor inhibition is attributed to a hyperpolarizing receptor potential. It has been proposed that a Ca2+-dependent K+(KCa) conductance plays a key role in odor inhibition, both in toad and rat isolated olfactory neurons. The mechanism underlying odor inhibition has remained elusive. We assessed its study using various pharmacological agents and caged compounds for cAMP, Ca2+, and inositol 1,4,5-triphosphate (InsP3) on isolated toad ORNs. The odor-triggered KCacurrent was reduced on exposing the cell either to the CNG channel blocker LY83583 (20 μM) or to the adenylyl cyclase inhibitor SQ22536 (100 μM). Photorelease of caged Ca2+activated a Cl−current sensitive to niflumic acid (10 μM) and a K+current blockable by charybdotoxin (20 nM) and iberiotoxin (20 nM). In contrast, photoreleased Ca2+had no effect on cells missing their cilia, indicating that these conductances are confined to the cilia. Photorelease of cAMP induced a charybdotoxin-sensitive K+current in intact ORNs. Photorelease of InsP3did not increase the membrane conductance of olfactory neurons, arguing against a direct role of InsP3in chemotransduction. We conclude that a cAMP cascade mediates the activation of the ciliary Ca2+-dependent K+current and that the Ca2+ions that activate the inhibitory current enter the cilia through CNG channels.
Topographic Organization for Delayed Saccades in Human Posterior Parietal Cortex
Authors: Schluppeck Denis , Glimcher Paul , Heeger David J.
Published: April 2005

Posterior parietal cortex (PPC) is thought to play a critical role in decision making, sensory attention, motor intention, and/or working memory. Research on the PPC in non-human primates has focused on the lateral intraparietal area (LIP) in the intraparietal sulcus (IPS). Neurons in LIP respond after the onset of visual targets, just before saccades to those targets, and during the delay period in between. To study the function of posterior parietal cortex in humans, it will be crucial to have a routine and reliable method for localizing specific parietal areas in individual subjects. Here, we show that human PPC contains at least two topographically organized regions, which are candidates for the human homologue of LIP. We mapped the topographic organization of human PPC for delayed (memory guided) saccades using fMRI. Subjects were instructed to fixate centrally while a peripheral target was briefly presented. After a further 3-s delay, subjects made a saccade to the remembered target location followed by a saccade back to fixation and a 1-s inter-trial interval. Targets appeared at successive locations “around the clock” (same eccentricity, ≈30° angular steps), to produce a traveling wave of activity in areas that are topographically organized. PPC exhibited topographic organization for delayed saccades. We defined two areas in each hemisphere that contained topographic maps of the contra-lateral visual field. These two areas were immediately rostral to V7 as defined by standard retinotopic mapping. The two areas were separated from each other and from V7 by reversals in visual field orientation. However, we leave open the possibility that these two areas will be further subdivided in future studies. Our results demonstrate that topographic maps tile the cortex continuously from V1 well into PPC.
Glycobiology of Head and Neck Squamous Epithelia and Carcinomas
Authors: Plzák Jan , Smetana Jr. Karel , Chovanec Martin , Betka Jan
Published: April 2005

An impressive variety of regulatory processes including cell adhesion and migration, proliferation, apoptosis and differentiation folding and routing of glycoproteins have been found to be mediated by specific lectin-carbohydrate interactions. This article summarizes the data on glycobiological aspects of differentiation of squamous epithelia in the head and neck region under physiological conditions and in cancer. The possible function of lectins in tumor development and invasiveness is debated. Introduction of labeled endogenous lectins as a tool for the study of functional glycomics at the cellular level in head and neck squamous epithelia and carcinomas enables a complex interpretation of studied data because these lectins are normally occurring in these tissues. The lectinology of Langerhans cells in head and neck squamous epithelia and carcinoma is also mentioned. Finally, the use of the described data in the diagnosis and prospectively in the treatment of head and neck squamous cell carcinoma is shown.
Tissue Microarray Analysis of C-MYC Oncogene Copy Number Changes in Larynx Carcinoma
Authors: Koynova Denitsa Krasimirova , Tsenova Vesselina Sainova , Toncheva Draga Ivanova
Published: April 2005

Purpose of the Study: Copy number changes and structural rearrangements of 8q in tumors from the head and neck region have been reported by numerous studies. To give better insights into the role of 8q abnormalities in larynx carcinoma, C-MYC copy number changes were studied in a large number of tumor materials. Procedures: Fluorescent in situ hybridization with DNA locus-specific probe for C-MYC genewas applied on tissue microarrays presented by 863 larynx tumors. Results: 32.02% had increased copy number of C-MYC. Of these, 6.16% hadamplification and 25.86% had C-MYC gains. The analysis revealed a significant difference in the frequency of gains in primary and advanced tumors. Furthermore, we observed an association of gains with advanced clinical stage (I–III to IV). No association was found between the frequency of oncogene amplification and the tumor phenotype. Conclusions:These results suggest that the C-MYC gains are significant for the larynx tumor progression.
Temporal Changes in Postural Sway Caused by Ultrashort-Acting Hypnotics: Triazolam and Zolpidem
Authors: Nakamura M. , Ishii M. , Niwa Y. , Yamazaki M. , Ito H.
Published: April 2005

Two ultrashort-acting hypnotics, triazolam 0.25 mg and zolpidem 10 mg, were studied for their effects on equilibrium function in humans. Eight healthy male subjects participated in a double-blind, placebo-controlled study after informed consent. They subjected to static equilibrium tests, oculomotor tests and an assay of drug concentrations in the blood. Zolpidem was statistically significant in postural sway in tandem stance test, as defined by parametric values of tracing sum length and polygonal area of foot pressure center measured by a gait analysis system. In the tandem stance test, triazolam was statistically significant in postural sway only as defined by the polygonal area. However, in the Romberg test, the only statistically significant difference in zolpidem use was observed in polygonal area values. Blood concentrations of triazolam and zolpidem were found to closely correlate with the extent of postural sway in both tandem stance and Romberg tests. In this study, zolpidem with minimal muscle-relaxant effect incurred imbalance more extensively than triazolam, which is known for its effect of muscle relaxation. In addition, gaze deviation nystagmus was observed only in zolpidem use in 5 of 8 subjects (62.5%). From these results, it is suggested that in the use of hypnotics, sway derives from the suppression of the central nervous system relevant to awakening rather than from muscle relaxation. The prior reference to blood concentrations of hypnotics should help improve safety care in minimizing loss of balance control and possible fall.
Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: A Report Three Years into the Program
Authors: Cavarzere Paolo , Camilot Marta , Teofoli Francesca , Tatò Luciano
Published: April 2005

Aims: To evaluate the incidence of congenital adrenal hyperplasia (CAH) in the Northern Italian population and the efficiency of the North-Eastern Italy screening program. To adjust cut-off levels for 17-hydroxyprogesterone (17-OHP) in relation to gestational age and birth weight, comparing the benefits in terms of reduction of recall rates with the two approaches and ultimately choosing the better of the two. Subjects and Methods: Since September 2001, blood samples from neonates born in North-Eastern Italy have been screened with a fluoroimmunoassay method for 17-OHP determination (DELFIA). A preliminary cut-off level of ≧30 nmol/l was set both for term and preterm newborns. The values of 17-OHP were analysed usingstatistical methods in relation to gestational age and birth weight in order to modify the cut-off on the basis of our data. Results: After 33 months of screening we screened 128,282 newborns and detected 6 affected babies. During the first 8 months of screening among the recalled babies, 89.6 and 78.1% were preterm and low-birth-weight newborns, respectively, with a recall rate of 2.59% for premature neonates and of 4.94% for babies with birth weights <2,500 g. We chose a new cut-off value of 50 nmol/l for preterm newborns only and, after 4 months, the recall rate was reduced to 0.83% for these infantsand to 1.83% for low-birth-weight infants. Conclusion: After 33 months of screening for CAH in North-Eastern Italy, we report an incidence of 1:21,380. In 5 out of 6 affected babies, the diagnosis was established only after a positive screening test, which prevented a severe salt-wasting crisis in these babies. The cut-off level related to gestational age led to a significant reduction in the number of false-positives among preterm babies.We therefore intend to continue with the screening program for CAH in North-Eastern Italy, keeping a gestational-age-related cut-off in the hope that our data may encourage a national screening program for CAH.
Venous Air Embolism during Deep Brain Stimulation Surgery in an Awake Supine Patient
Authors: Deogaonkar Anupa , Avitsian Rafi , Henderson Jaimie M. , Schubert Armin
Published: April 2005

Deep brain stimulation (DBS) of the subthalamic nucleus and globus pallidus is used to improve Parkinsonian symptoms and reduce levodopa-induced motor complications in Parkinson’s disease (PD). This procedure is usually performed with minimal or no sedation to allow accurate feedback from patients during surgery. Venous air embolism (VAE) has been previously reported in patients undergoing awake neurosurgical procedures for brain tumors or pallidotomy for PD. We describe a case of intraoperative VAE in an awake, supine patient while undergoing DBS surgery for PD who presented with coughing, tachypnea and hypoxemia. The difference in clinical presentation between VAE in awake vs. anesthetized patients is discussed as are intraoperative monitoring techniques and management options.
Withdrawal of Warfarin prior to a Surgical Procedure: Time to Follow the Guidelines?
Authors: Akopov Sergey E. , Suzuki Shuichi , Fredieu Andre , Kidwell Chelsea S. , Saver Jeffrey L. , Cohen Stanley N.
Published: April 2005

Background and Objective: Patients with cardiogenic sources of embolism may be at increased risk of cerebral infarction when anticoagulation therapy is suspended for surgical procedures. The purpose of this study was to determine frequency of cardioembolic cerebral infarction during periprocedural warfarin withdrawal. Methods: Retrospective analysis of prospective cerebral infarction registry data from two tertiary medical centers. Results: Over a 12-month period, 14 cases of cardioembolic cerebral infarction occurring during the period of warfarin withdrawal for a medical procedure were observed, accounting for 7.1% of the 197 cardioembolic cerebral infarctions encountered. Across all patients, cerebral infarctions developed an average of 5.4 days after the last dose of warfarin (range 3–8). Among the 14 patients (8 males and 6 females) with warfarin cessation-related infarcts, age ranged from 54 to 91 years. Each had been on chronic anticoagulation with warfarin for more than 1 year. Retrospective analysis suggested that all these cerebral infarctions had been potentially preventable. In each case, either the planned procedure did not require discontinuation of warfarin or, when withdrawal was required, no bridging, parenteral anticoagulation was provided to lessen the risk during the warfarin-free period. Conclusion: Patients at high risk of cardioembolic cerebral infarction may benefit from more intensive management strategies to reduce cerebral infarction risk during periprocedural periods.
Urinary Excretion of Transferrin and Orosomucoid Are Increased after Acute Protein Loading in Healthy Subjects
Authors: Koshimura Jun , Narita Takuma , Sasaki Hiroshi , Hosoba Mihoko , Yoshioka Naomi , Shimotomai Takashi , Fujita Hiroki , Kakei Masafumi , Ito Seiki
Published: April 2005

Background/Aims: The aim of this study was to elucidate what kind of plasma proteins would change their urinary excretions when the glomerular filtration rate (GFR) was increased. Methods: We measured urinary excretions of three plasma proteins with different molecular radii (MR) and isoelectric points (pI): albumin, orosomucoid (OM) and transferrin (Tf), after acute protein loading in healthy subjects. Results: Urinary excretion of OM with more anioic charge and smaller MR than albumin, and Tf with more cationic charge and slightly larger molecular weight than albumin, significantly increased in parallel with increased creatinine clearances after acute protein loading. These renal responses returned to basal levels 9 h after protein ingestion. In contrast, increases in urinary excretion of albumin were not observed. Conclusion: Because these findings could not be explained by changes in either size or charge selectivity of shunt pores in the glomerular capillary wall, it is suggested that urinary excretion of albumin may have a special property that distinguishes it from other plasma proteins and may be a less sensitive marker to reflect changes in renal hemodynamics than the other plasma proteins.
Influence of Intravenous Drug Abuse on Vascular Access Placement and Survival in HIV-Seropositive Patients
Authors: Eustace Joseph A. , Gregory Peter C. , Krishnan Mahesh , Ni Wen , Kuhn Doreen M. , Astor Brad C. , Scheel Jr. Paul J.
Published: April 2005

Background: The influence of intravenous drug abuse (IVDA) on hemodialysis access placement practices and access survival in HIV-infected patients is unknown. Methods: We conducted a retrospective study of 60, HIV seropositive, maintenance hemodialysis patients. Type of access and assisted access survival (measured from date of placement) were compared in those with (77%) and without (23%) a history of IVDA. Results: Mean age was 37.8 years, mean baseline serum albumin was 2.9 g/dl and median CD4 count was 222 cells/mm3. Fifteen patients, all IVDA, were dialyzed using only tunneled catheters (median number of catheters per person (range): 2.5 (1–11)). There were longer delays in creation of a permanent access (p = 0.08), but no difference in the type of permanent access placed in IVDA versus the non-IVDA group. Over 1,051 cumulative months of access follow-up, 134 tunneled catheters, 28 grafts and 19 fistulae were placed, with observed failure rates of 1 per 4.7 access-months, 1 per 19.7 access-months, 1 per 38.2 access-months, respectively. The adjusted relative hazard of access failure for grafts versus catheters was 0.41 (95% CI: 0.23, 0.72; p = 0.002) and for fistulae versus catheters was 0.21 (95% CI: 0.08, 0.52; p = 0.001). Thirty-two percent of accesses were removed due to infection, an infection removal rate for catheters of 1 per 7.8 access-months and for grafts of 1 per 62.5 access-months; all graft infections occurred in the IVDA group. No fistula was removed due to infection. Conclusion: Fistulae are the first line of choice for hemodialysis access in HIV-seropositive patients regardless of IVDA history; if not feasible, graft placement in non-IVDA or abstinent IVDA patients is recommended. In those with active IVDA, the optimal method of renal replacement therapy and type of hemodialysis access remain uncertain.
Limitations of CA125 as an Index of Peritoneal Mesothelial Cell Mass
Authors: Bręborowicz Andrzej , Bręborowicz Maciej , Pyda Malgorzata , Połubinska Alicja , Oreopoulos Dimitrios
Published: April 2005

Background: CA125 is commonly used as an index of the mesothelial cell mass in patients treated with peritoneal dialysis. However, we have no data that show a direct relationship between the number of mesothelial cells, their functional properties, and the amount of CA125 produced in these cells. Methods: Experiments were performed on primary in vitro cultures of human peritoneal mesothelial cells obtained from 32 donors of various ages and of both sexes. Spontaneous release of CA125 from the confluent mesothelial cells was measured and correlated with the number of cells in monolayers and with their functional properties. We also studied acute effects of cytokines (IL-1β, TNF-α, and INF-γ) and the chronic effects of glucose (45 mM) on the CA125 content in mesothelial cells and the release of this antigen from their cytosol. Results: Cells from older donors released more CA125, but we found no correlation between the number of cells and the amount of CA125 released from their cytosol. The synthesis of CA125 in mesothelial cells does not correlate with the amount of monocyte chemoattractant protein 1 or interleukin-6 produced in these cells. Acute exposure to cytokines did not modify CA125 content or its release from mesothelial cells. Chronic exposure of mesothelial cells for 4 weeks to glucose (45 mM) decreased the CA125 content of their cytosol and the release of this antigen into the culture medium. Mannitol, at the same concentration and under the same conditions, did not produce these effects, namely a decrease in the CA125 content in the cytosol or its release into the cultural medium. Conclusions: The amount of CA125 released from mesothelial cells is not a good index of their number or their functional properties, because the CA125 release depends not only on the number of cells, but also on their properties. Furthermore, the process is affected by the age of the cell donor and environmental factors such as a high glucose content. The results of this study show the limitations of CA125 as an index of the mesothelial cell mass and viability.
Two Visual Processing Pathways Are Targeted by Gonadotropin-Releasing Hormone in the Retina
Authors: Grens Kerry E. , Greenwood Anna K. , Fernald Russell D.
Published: April 2005

In fish the terminal nerve is comprised of a group of cells with somata adjacent to the olfactory bulb and processes that extend both anteriorly to the olfactory mucosa and posteriorly to the telencephalon. In teleost fish an additional group of axons extends along the optic tract and delivers putative neuromodulators to the retina. One peptide – gonadotropin-releasing hormone (GnRH) – has been implicated as a prime candidate neuromodulator based on electrophysiological evidence that exogenous application influences neural activity. Here we describe the expression patterns of two GnRH receptor subtypes in the retina of a teleost fish, Astatotilapia (Haplochromis) burtoni. The type 1 GnRH receptor (GnRH-R1) was expressed in cells of the amacrine cell layer – where lateral inputs affect the flow of visual information from photoreceptors to the brain – and in a distribution and location pattern similar to dopaminergic interplexiform cells. Immunohistochemical labeling of GnRH fibers revealed varicosities along terminal nerve axons near the amacrine cell layer and near cells immunoreactive for tyrosine hydroxylase, a dopaminergic cell marker. This finding supports an existing model that the terminal nerve forms synapses with dopaminergic interplexiform cells. Surprisingly, the type 2 GnRH receptor (GnRH-R2) was abundantly expressed in ganglion cells, which lie along the direct pathway of visual information to the brain. These data suggest that GnRH from the TN could broadly influence processing of retinal signals both in lateral processing circuits through GnRH-R1 and in the vertical throughput pathway through GnRH-R2.
Interspecific Variation in Photo-Induced GnRH Plasticity among Nomadic Cardueline Finches
Authors: Pereyra Maria Elena , Sharbaugh Susan M. , Hahn Thomas P.
Published: April 2005

Changes in response to photoperiod are of fundamental importance to seasonal cycles in avian reproductive development. In this study we present data on photo-induced changes in gonadotropin-releasing hormone (GnRH) immunoreactivity associated with the development of photorefractoriness in males of 3 closely related species of cardueline finch: common redpoll (Carduelis flammea), pine siskin (C. pinus) and white-winged crossbill (Loxia leucoptera). All are nomadic, mid- to high-latitude breeders with varying levels of reproductive flexibility: redpolls are typically seasonal, pine siskins more flexibly seasonal and white-winged crossbills temporally opportunistic. Males were exposed to either long (20L:4D) or short days (5L:19D), beginning in January, and GnRH was assessed via immunocytochemistry 4.5 months later. Plasma LH, testis size, and molt score were also measured. Significant reductions in the number of irGnRH cells detected, cross-sectional cell area and optical density of these cells occurred in both redpolls and siskins on long, as compared with short, days. These decreases in irGnRH, coupled with spontaneous testicular regression and onset of molt were consistent with the development of absolute photorefractoriness on constant long days. In contrast, the tendency for numbers of GnRH immunopositive cells and mean measures of GnRH immunoreactivity (cell area, optical density and axonal fiber density) to decrease were much more moderate in white-winged crossbills held on long versus short days. Although none of the four measures of GnRH immunoreactivity differed significantly between treatments in crossbills, significant shifts in the frequency distribution of irGnRH neurons to include greater numbers of less immunoreactive cells suggested that antigenic GnRH content was reduced in many cells. These photo-induced shifts in optical densities of GnRH cells in long-day, as compared with short-day crossbills followed, to a lesser extent, the pattern in pine siskins and common redpolls. For all three species, patterns of decrease in GnRH immunoreactivity, gonadal regression and molt suggest that some form of refractoriness to photostimulation develops on constant long days. However, more moderate tendencies for GnRH immunoreactivity to decrease in white-winged crossbills, coupled with limited gonadal regression and molt on long days suggest that absolute photorefractoriness might develop more slowly in this taxon than in others, or alternatively, a condition arises that is more similar to relative photorefractoriness. These data indicate that relatively small differences in the response of the neuroendocrine system to stimulatory cues such as day length may lead to remarkably different capabilities for reproductive flexibility even within a closely related family of birds.
High-Density Lipoproteins Prevent the Oxidized Low-Density Lipoprotein–Induced Endothelial Growth Factor Receptor Activation and Subsequent Matrix Metalloproteinase-2 Upregulation
Authors: Robbesyn Fanny , Augé Nathalie , Vindis Cécile , Cantero Anne-Valérie , Barbaras Ronald , Negre-Salvayre Anne , Salvayre Robert
Published: April 2005

Objectives—The atherogenic oxidized low-density lipoprotein (oxLDL) induces the formation of carbonyl-protein adducts and activates the endothelial growth factor receptor (EGFR) signaling pathway, which is now regarded as a central element for signal transduction. We aimed to investigate whether and by which mechanism the anti-atherogenic high-density lipoprotein (HDL) prevents these effects of oxLDL.

Methods and Results—In vascular cultured cells, HDL and apolipoprotein A-I inhibit oxLDL-induced EGFR activation and subsequent signaling by acting through 2 separate mechanisms. First, HDL, like the aldehyde scavenger dinitrophenyl hydrazine, prevented the formation of oxLDL-induced carbonyl–protein adducts and 4-hydroxynonenal (HNE)–EGFR adducts. Secondly, HDL enhanced the cellular antioxidant defenses by preventing (through a scavenger receptor class B-1 (SR-BI)–dependent mechanism) the increase of intracellular reactive oxygen species (ROS) and subsequent EGFR activation triggered by oxLDL or H2O2. A pharmacological approach suggests that this protective effect of HDL is independent of cellular glutathione level and glutathione peroxidase activity, but it requires catalase activity. Finally, we report that oxLDL upregulates both membrane type 1 (MT1)-matrix metalloproteinase-1 (MT1-MMP) and MMP-2 through an EGFR-dependent mechanism and that HDL inhibits these events.

Conclusions—HDLs block in vitro oxLDL-induced EGFR signaling and subsequent MMP-2 activation by inhibiting carbonyl adducts formation and cellular oxidative stress. These effects of HDL may participate to reduce cell activation, excessive remodeling, and alteration of the vascular wall.
Vascular Implications of the Krüppel-Like Family of Transcription Factors
Authors: Suzuki Toru , Aizawa Kenichi , Matsumura Takayoshi , Nagai Ryozo
Published: April 2005

The Krüppel-like factor (KLF) family is a recently highlighted group of zinc finger transcription factors given their important biological roles which include the vasculature. KLF2, KLF4, KLF5, and KLF6 are notable factors that have been implicated in developmental as well as pathological vascular processes. In this brief review, we provide an up-to-date summary of the physiological functions and cellular effects as well as transcriptional regulatory mechanisms of the vascular KLFs. Through such, we aim to provide a working view for understanding the pathological actions of KLFs in the vasculature.
Adenovirus-Mediated Overexpression of
O
-GlcNAcase Improves Contractile Function in the Diabetic Heart
Authors: Hu Ying , Belke Darrell , Suarez Jorge , Swanson Eric , Clark Raymond , Hoshijima Masahiko , Dillmann Wolfgang H.
Published: April 2005

To examine whether excessive protein
O
-GlcNAcylation plays a role in the dysfunction of the diabetic heart, we delivered adenovirus expressing
O
-GlcNAcase (Adv-GCA) into the myocardium of STZ-induced diabetic mice. Our results indicated that excessive cellular
O
-GlcNAcylation exists in the diabetic heart, and that in vivo GCA overexpression reduces overall cellular
O
-GlcNAcylation. Myocytes isolated from diabetic hearts receiving Adv-GCA exhibited improved calcium transients with a significantly shortened T
decay
(
P
<0.01) and increased sarcoplasmic reticulum Ca
2+
load (
P
<0.01). These myocytes also demonstrated improved contractility including a significant increase in +dL/dt and −dL/dt and greater fractional shortening as measured by edge detection (
P
<0.01). In isolated perfused hearts, developed pressure and −dP/dt were significantly improved in diabetic hearts receiving Adv-GCA (
P
<0.05). These hearts also exhibited a 40% increase in SERCA2a expression. Phospholamban protein expression was reduced 50%, but the phosphorylated form was increased 2-fold in the diabetic hearts receiving Adv-GCA. We conclude that excess
O
-GlcNAcylation in the diabetic heart contributes to cardiac dysfunction, and reducing this excess cellular
O
-GlcNAcylation has beneficial effects on calcium handling and diabetic cardiac function.
Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation
Authors: Barth Andreas S. , Merk Sylvia , Arnoldi Elisabeth , Zwermann Ludwig , Kloos Patrick , Gebauer Mathias , Steinmeyer Klaus , Bleich Markus , Kääb Stefan , Hinterseer Martin , Kartmann Heike , Kreuzer Eckart , Dugas Martin , Steinbeck Gerhard , Nabauer Michael
Published: April 2005

Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium.
Long-Term Inhibition of RhoA Attenuates Vascular Contractility by Enhancing Endothelial NO Production in an Intact Rabbit Mesenteric Artery
Authors: Shiga Noriko , Hirano Katsuya , Hirano Mayumi , Nishimura Junji , Nawata Hajime , Kanaide Hideo
Published: April 2005

RhoA plays a critical role in regulating NO production in cultured endothelial cells. To determine its role in in situ endothelial cells, we investigated the effects of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and a RhoA-binding domain of Rho-kinase (RB) on vascular contractility in the isolated rabbit mesenteric artery. Ex vivo treatment of the strips with 3×10
−5
mol/L simvastatin and fluvastatin for ≈24 to 30 hours significantly attenuated the contractile response to phenylephrine and high K
+
in the presence of endothelium. The addition of
N
ω
-nitro-
l
-arginine methyl ester and the removal of endothelium abolished the attenuation of the contractile response. The cotreatment with geranylgeranyl pyrophosphate prevented the statin-induced attenuation of the contractile response, whereas geranylgeranyl transferase inhibitor mimicked the effect of simvastatin. Treatment with simvastatin enhanced the bradykinin-induced endothelium-dependent relaxation in the mesenteric artery, whereas it had no effect on the bradykinin-induced [Ca
2+
]
i
elevation in endothelial cells of the aortic valves. Introduction of RB to the strips using a cell-penetrating peptide of Tat protein (TATHA-RB) attenuated the contractile responses in a NO-dependent manner. However, a Rac1/Cdc42-binding fragment of p21-activated protein kinase, RB without Tat peptide or TATHA-protein A had no effect. The in vivo treatment of rabbit with simvastatin and TATHA-RB attenuated the contractility in a NO-dependent manner. Simvastatin and TATHA-RB significantly upregulated eNOS in the rabbit mesenteric artery. The present study provides the first evidence that RhoA plays a physiological role in suppressing NO production in in situ endothelial cells.
The Value of XYZ/2 Technique Compared With Computer-Assisted Volumetric Analysis to Estimate the Volume of Chronic Subdural Hematoma
Authors: Sucu Hasan Kamil , Gokmen Metin , Gelal Fazil
Published: April 2005

Background and Purpose—

A simple estimation method of intracerebral hematoma volume known as XYZ/2 method has been described previously. This method has also been shown to be valid for the estimation of acute subdural hematoma volume. However, chronic subdural hematomas differ in shape and extension from acute subdural hematomas, which makes the validity of the same method in the estimation of hematoma volume questionable. We aimed to determine the value of XYZ/2 method to estimate the volume of chronic subdural hematoma when compared with computer-assisted volumetric analysis.

Methods—

Computed tomography scans of 28 patients with unilateral hemispheric chronic subdural hematoma were reviewed. Hematoma volumes were measured using 5 different XYZ/2 formulas and compared with volumes measured by computer-assisted analysis. Nonparametric correlation coefficient (Spearman’s ρ) was used in statistical comparison.

Results—

All 5 formulas showed excellent correlation with the gold standard, proving the validity of XYZ/2 method in the estimation of chronic subdural hematoma volume (level of significance <0.001). Our results suggest that maximum hematoma length and width, which are not necessarily on the same slice, should be used rather than length and width of hematoma on the central slice when using XYZ/2 method in patients with chronic subdural hematoma.

Conclusion—

This study proves the validity of XYZ/2 technique for the estimation of chronic subdural hematoma volume as well.
Screening for Aspirin Responsiveness After Transient Ischemic Attack and Stroke
Authors: Harrison Paul , Segal Helen , Blasbery Kevin , Furtado Charlene , Silver Louise , Rothwell Peter M.
Published: April 2005

Background and Purpose—

Recent studies suggest that patients who do not respond to aspirin (ASA) therapy may be at increased risk of ischemic vascular events. The availability of simple to use point-of-care (POC) platelet function tests now potentially allows aspirin nonresponsiveness to be identified in routine clinical practice. However, there are very few data on whether the different tests produce consistent results. We therefore compared 2 POC tests (PFA-100 device and the Ultegra-RPFA [RPFA]) with conventional light transmission aggregometry (LTA).

Methods—

Platelet function was assessed by all 3 tests in 100 patients receiving low-dose ASA therapy after transient ischemic attack (TIA) or ischemic stroke.

Results—

The incidence of ASA nonresponsiveness was 17% by the RPFA and 22% by the PFA-100, compared with only 5% by LTA (ie, as defined with both arachidonic acid and ADP). Agreement between the RPFA and the PFA-100 and arachidonic acid induced LTA was poor (κ=0.16, 95% CI, −0.08 to 0.39,
P
=0.11; and κ=0.09 −0.12 to 0.30,
P
=0.32, respectively). Agreement between the 2 POC tests was also poor (κ=0.14, −0.08 to 0.36,
P
=0.15). Only 2% of patients were aspirin nonresponders by all 3 tests.

Conclusions—

The prevalence of apparent ASA nonresponsiveness was higher with both the POC tests than with LTA. However, agreement between the tests was poor and very few patients were ASA nonresponsive by all 3 tests. Aspirin nonresponsiveness is therefore highly test-specific and large prospective studies will be required to determine the prognostic value of each of the separate tests.
Oxygen Glucose Deprivation Switches the Transport of tPA Across the Blood–Brain Barrier From an LRP-Dependent to an Increased LRP-Independent Process
Authors: Benchenane Karim , Berezowski Vincent , Fernández-Monreal Mónica , Brillault Julien , Valable Samuel , Dehouck Marie-Pierre , Cecchelli Roméo , Vivien Denis , Touzani Omar , Ali Carine
Published: April 2005

Background and Purpose—

Despite uncontroversial benefit from its thrombolytic activity, the documented neurotoxic effect of tissue plasminogen activator (tPA) raises an important issue: the current emergency stroke treatment might not be optimum if exogenous tPA can enter the brain and thus add to the deleterious effects of endogenous tPA within the cerebral parenchyma. Here, we aimed at determining whether vascular tPA crosses the blood–brain barrier (BBB) during cerebral ischemia, and if so, by which mechanism.

Methods—

First, BBB permeability was assessed in vivo by measuring Evans Blue extravasation following intravenous injection at 0 or 3 hours after middle cerebral artery electrocoagulation in mice. Second, the passage of vascular tPA was investigated in an in vitro model of BBB, subjected or not to oxygen and glucose deprivation (OGD).

Results—

We first demonstrated that after focal permanent ischemia in mice, the BBB remains impermeable to Evans Blue in the early phase (relative to the therapeutic window of tPA), whereas at later time points massive Evans Blue extravasation occurs. Then, the passage of tPA during these 2 phases, was investigated in vitro and we show that in control conditions, tPA crosses the intact BBB by a low-density lipoprotein (LDL) receptor-related protein (LRP)-dependent transcytosis, whereas OGD leads to an exacerbation of tPA passage, which switches to a LRP-independent process.

Conclusion—

We evidence 2 different mechanisms through which vascular tPA can reach the brain parenchyma, depending on the state of the BBB. As discussed, these data show the importance of taking the side effects of blood-derived tPA into account and offer a basis to improve the current thrombolytic strategy.
Impaired Cerebral Vasoreactivity in a Transgenic Mouse Model of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Arteriopathy
Authors: Lacombe Pierre , Oligo Charleen , Domenga Valérie , Tournier-Lasserve Elisabeth , Joutel Anne
Published: April 2005

Background and Purpose—

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and dementia. The disease is caused by highly stereotyped mutations in
NOTCH3
, which is restrictively expressed in vascular smooth muscle cells (VSMCs). The mechanisms of compromised cerebral hemodynamics in CADASIL remain to be elucidated. We tested the hypothesis that mutant NOTCH3 impairs the vasomotor function of cerebral vessels.

Methods—

Vasomotor function was examined in vivo in transgenic mice expressing a mutant NOTCH3 in VSMCs (TgNotch3R90C). Mice develop an age-dependent arteriopathy similar to that seen in CADASIL, without brain parenchyma lesions. Using laser-Doppler flowmetry, we assessed in awake TgNotch3R90C mice and wild-type littermates the cerebrovascular reactivity to 2 potent vasodilator stimuli (acetazolamide and hypercapnia) and cerebral blood flow (CBF) autoregulation during stepwise blood pressure elevations and reductions. Mice were studied at 18 months of age, when the CADASIL features are apparent, and at 10 months of age, before their appearance.

Results—

Eighteen-month-old TgNotch3R90C mice showed reduced responses to hypercapnia and acetazolamide, higher cerebrovascular resistance during hypertension, and their lower limit of CBF autoregulation was shifted to higher blood pressures. Cerebrovascular responses were similarly impaired in 10-month-old TgNotch3R90C mice.

Conclusions—

Cerebrovascular reactivity is compromised early in TgNotch3R90C mice. The data show an impaired autoregulation and are suggestive of a decreased relaxation or increased resistance of cerebral vessels. Our findings indicate that vascular dysfunction is an early pathogenic event that may promote the subsequent development of brain ischemia in CADASIL.
Trends and Variability in U.S. Corn Yields Over the Twentieth Century
Authors: Kucharik Christopher J. , Ramankutty Navin
Published: April 2005

The United States is currently responsible for 40%–45% of the world’s corn supply and 70% of total global exports [the U.S. Department of Agriculture–National Agricultural Statistics Service (USDA–NASS)]. Therefore, analyses of the spatial and temporal patterns of historical U.S. corn yields might provide insight into future crop-production potential and food security. In this study, county-level maize yield data from 1910 to 2001 were used to characterize the spatial heterogeneity of yield growth rates and interannual yield variability across the U.S. Corn Belt.

Widespread decadal-scale changes in corn yield variability and yield growth rates have occurred since the 1930s across the Corn Belt, but the response has varied substantially with geographic location. Northern portions of the Great Plains have experienced consistently high interannual corn yield variability, averaging 30%–40% relative to the mean. Increasing usage of irrigation in Nebraska, Kansas, and Texas, since the 1950s, has helped boost yields by 75%–90% over rain-fed corn, creating a yield gap of 2–4 T ha−1 between irrigated and nonirrigated corn that could potentially be exploited in other regions. Furthermore, irrigation has reduced interannual variability by a factor of 3 in these same regions. A small region from eastern Iowa into northern Illinois and southern Wisconsin has experienced minimal interannual yield variability, averaging only 6%–10% relative to mean yields.

This paper shows that the choice of time period used for statistical analysis impacted conclusions drawn about twentieth-century trends in corn yield variability. Widespread increases in yield variability were apparent from 1950 onward, but were not significant over the entire 1930–2001 period. There is also evidence that yield variability decreased from the early 1990s to 2001. Corn yield growth rates peaked at an annual-average rate of 3%–5% in the 1960s (124.5 kg ha−1 yr−1), but have steadily declined to a relative rate of 0.78% yr−1 (49.2 kg ha−1 yr−1) during the 1990s. A general inverse relationship between increasing corn yield and decreasing yield growth rates was noted after county-level yields reached 4 T ha−1, suggesting that widespread, significant increases in corn yield are not likely to take place in the future, particularly on irrigated land, without a second agricultural revolution.
Some Characteristics of Model-Predicted Precipitation during the Summer Monsoon over India
Authors: Basu B. K.
Published: April 2005

For the summer monsoon seasons of 1995, 1996, and 1997 the day-1 to day-4 forecasts of precipitation from both the National Centre for Medium Range Weather Forecasting (NCMRWF) and the European Centre for Medium-Range Forecasts (ECMWF) models reproduce the main features of the observed precipitation pattern when averaged over the whole season. On average, less than 30% of all rain gauge stations in India report rain on a given day during the monsoon season. The number of observed rainy days increases to 41% after spatial averaging over ECMWF model grid boxes and to 50% after spatial averaging over NCMRWF model grid boxes. The NCMRWF model forecasts have 10%–15% more rainy days, mostly in the light or moderate precipitation categories, when compared with the spatial average of observed values. Seasonal accumulated values of all of India’s average precipitation show a slight increase with the forecast lead time for the NCMRWF model and a small decrease for the ECMWF model. The weekly accumulated values of forecast precipitation from both models, averaged over the whole of India, are in good phase relationship (∼0.9 in most cases) with the observed value for forecasts with a lead time up to day 4. Values of statistical parameters, based on the frequency of occurrence in various classes, indicate that the NCMRWF model has some skill in predicting precipitation over India during the summer monsoon. The NCMRWF model forecasts have higher trend correlation with the observed precipitation over India than do the ECMWF model forecasts. The mean error in precipitation is, however, much less in the ECMWF model forecasts, and the spatial distribution of seasonal average medium-range forecasts of ECMWF is closer to that observed along the west coast mountain ridgeline.
Radar Refractivity Retrieval: Validation and Application to Short-Term Forecasting
Authors: Weckwerth Tammy M. , Pettet Crystalyne R. , Fabry Frédéric , Park Shin Ju , LeMone Margaret A. , Wilson James W.
Published: April 2005

This study will validate the S-band dual-polarization Doppler radar (S-Pol) radar refractivity retrieval using measurements from the International H2O Project conducted in the southern Great Plains in May–June 2002. The range of refractivity measurements during this project extended out to 40–60 km from the radar. Comparisons between the radar refractivity field and fixed and mobile mesonet refractivity values within the S-Pol refractivity domain show a strong correlation. Comparisons between the radar refractivity field and low-flying aircraft also show high correlations. Thus, the radar refractivity retrieval provides a good representation of low-level atmospheric refractivity. Numerous instruments that profile the temperature and moisture are also compared with the refractivity field. Radiosonde measurements, Atmospheric Emitted Radiance Interferometers, and a vertical-pointing Raman lidar show good agreement, especially at low levels. Under most daytime summertime conditions, radar refractivity measurements are representative of an ∼250-m-deep layer. Analyses are also performed on the utility of refractivity for short-term forecasting applications. It is found that the refractivity field may detect low-level boundaries prior to the more traditional radar reflectivity and Doppler velocity fields showing their existence. Data from two days on which convection initiated within S-Pol refractivity range suggest that the refractivity field may exhibit some potential utility in forecasting convection initiation. This study suggests that unprecedented advances in mapping near-surface water vapor and subsequent improvements in predicting convective storms could result from implementing the radar refractivity retrieval on the national network of operational radars.
Simultaneous Observations of Cirrus Clouds with a Millimeter-Wave Radar and the MU Radar
Authors: Wada Eiko , Hashiguchi Hiroyuki , Yamamoto Masayuki K. , Teshiba Michihiro , Fukao Shoichiro
Published: April 2005

Observations of frontal cirrus clouds were conducted with the scanning millimeter-wave radar at the Shigaraki Middle and Upper Atmosphere (MU) Radar Observatory in Shiga, Japan, during 30 September–13 October 2000. The three-dimensional background winds were also observed with the very high frequency (VHF) band MU radar. Comparing the observational results of the two radars, it was found that the cirrus clouds appeared coincident with the layers of the strong vertical shear of the horizontal winds, and they developed and became thicker under the condition of the strong vertical shear of the horizontal wind and updraft. The result of the radiosonde observation indicated that Kelvin–Helmholtz instability (KHI) occurred at 8–9-km altitudes because of the strong vertical shear of the horizontal wind. The warm and moist air existed above the 8.5-km altitude, and the cold and dry air existed below the 8.5-km altitude. As a result of the airmass mixing of air above and below the 8.5-km altitudes, the cirrus clouds were formed. The updraft, which existed at 8.5–12-km altitude, caused the development of the cirrus clouds with the thickness of >2 km. By using the scanning millimeter-wave radar, the three-dimensional structure of cell echoes formed by KHI for the first time were successfully observed.