bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetics, conserved synteny and evolution of chicken fucosyltransferase genes compared to human
Authors: Coullin P. , Crooijmans R.P.M.A. , Fillon V. , Mollicone R. , Groenen M.A.M. , Adrien-Dehais C. , Bernheim A. , Zoorob R. , Oriol R. , Candelier J.-J.
Published: March 2004

Fucosyltransferases appeared early in evolution, since they are present from bacteria to primates and the genes are well conserved. The aim of this work was to study these genes in the bird group, which is particularly attractive for the comprehension of the evolution of the vertebrate genome. Twelve fucosyltransferase genes have been identified in man. The orthologues of theses genes were looked for in the chicken genome and cytogenetically localized by FISH. Three families of fucosyltransferases: α6-fucosyltransferases, α3/4-fucosyltransferases, and protein-O-fucosyltransferases, were identified in the chicken with their associated genes. The α2-fucosyltransferase family, although present in some invertebrates and amphibians was not found in birds. This absence, also observed in Drosophila, may correspond to a loss of these genes by negative selection. Of the eight chicken genes assigned, six fell on chromosome segments where conservation of synteny between human and chicken was already described. For the two remaining loci, FUT9 and FUT3/5/6, the location may correspond to a new small syntenic area or to an insertion. FUT4 and FUT3/5/6 were found on the same chicken chromosome. These results suggest a duplication of an ancestral gene, initially present on the same chromosome before separation during evolution. By extension, the results are in favour of a common ancestor for the α3-fucosyltransferase and the α4-fucosyltransferase activities. These observations suggest a general mechanism for the evolution of fucosyltransferase genes in vertebrates by duplication followed by divergent evolution.
Genomic organisation and chromosomal assignment of Odf2 (outer dense fiber 2), encoding the main component of sperm tail outer dense fibers and a centrosomal scaffold protein
Authors: Hoyer-Fender S. , Neesen J. , Szpirer J. , Szpirer C.
Published: March 2004

ODF2 (outer dense fiber 2) was first described as the main protein component of the sperm tail cytoskeleton, the outer dense fibers, but was shown recently to be a component of the centrosomal scaffold in chicken. In mouse two related Odf2 cDNA clones were isolated which have been suggested to be most likely the result of alternative splicing. We show here the exon/intron organisation of mouse Odf2 and demonstrate that alternative splicing results in related cDNA sequences and most likely explains, at least partially, the highly complex protein pattern detected on Western blots. Odf2 was mapped to rat chromosome 3 and more specifically by FISH analysis at bands 3q11→3q12. In addition, we demonstrate that ODF2 is indeed a component of the centrosome and the mitotic spindle poles in mammals.
Chromosomal localization of sixty autosomal loci in sheep (Ovis aries, 2n = 54) by fluorescence in situ hybridization and R-banding
Authors: Iannuzzi L. , Perucatti A. , Di Meo G.P. , Schibler L. , Incarnato D. , Cribiu E.P.
Published: March 2004

Sixty autosomal loci (5 type I and 55 type II) from 24 bovine syntenic groups, and previously FISH-mapped to goat and river buffalo chromosomes, were localized by fluorescence in situ on sheep (Ovis aries, 2n = 54) chromosomes, thereby notably extending the cytogenetic map of this economically important species. Caprine BAC clones were hybridized to R-banded chromosome preparations. FITC-signals and RBPI- banding (R-banding by late BrdU-incorporation and propidium iodide staining) were simultaneously visualized and captured by a colour CCD-camera. All mapped loci were localized on homoeologous chromosomes and chromosome regions (bands) of sheep, goat and river buffalo, further supporting chromosome and genetic (loci) homoeologies among bovids.
Morphological, chromosomal, and molecular evolution are uncoupled in pocket mice
Authors: Modi W.S.
Published: March 2004

C-, and G-banded chromosomes are presented for Perognathus amplus and Perognathus longimembris from Arizona, USA and Chaetodipus nelsoni from Coahuila, Mexico. The two species of Perognathus reveal similar C-band patterns, and extensive autosomal and X chromosome G-band identity with only pericentric inversions distinguishing pairs 4 and 6 and a difference in the morphology of pair 20. Three pairs of autosomal secondary constrictions were found in P. amplus and only one in P. longimembris. Only 50% of the amplus/longimembris G-banded karyotype could be aligned with that of C. nelsoni indicating extensive chromosomal restructuring has taken place since these genera last shared a common ancestor. A review of the literature suggests variable rates of morphological, chromosomal and molecular evolution in these animals.
Comparative cytogenetic analysis on four tree frog species (Anura, Hylidae, Hylinae) from Brazil
Authors: Kasahara S. , Zampieri Silva A.P. , Gruber S.L. , Haddad C.F.B.
Published: March 2004

A comparative cytogenetic analysis was carried out on four Hylinae tree frogs from Brazil (Aparasphenodon brunoi, Corythomantis greeningi, Osteocephalus langsdorffii, and Scinax fuscovarius) using Giemsa staining, BrdU replication banding, Ag-NOR staining, C-banding, DAPI and CMA3 fluorochrome staining, and fluorescence in situ hybridization (FISH) with an rDNA probe. All the species share closely similar 2n = 24 karyotypes, almost indistinguishable by standard staining. The technique of BrdU incorporation allowed the identification of each pair of homologs and the establishment of extensive homeology for the great majority of the chromosomes, mainly of A. brunoi, C. greeningi, and O. langsdorffii. Despite highly conserved replication banding patterns, the use of the other banding techniques disclosed some minor differences, which reinforces the importance of extensive cytogenetic analyses for the karyotypic characterization of Anuran species. The present cytogenetic data confirm the closer proximity of A. brunoi, C. greeningi, and O. langsdorffii, whereas S. fuscovarius is phylogenetically more distant.
Multicolor spectral karyotyping of rat chromosomes
Authors: Buwe A. , Steinlein C. , Koehler M.R. , Bar-Am I. , Katzin N. , Schmid M.
Published: March 2004

Rat and mouse have become important animal models to study various human diseases such as cancer. Cytogenetic analysis of the respective karyotypes is frequently required to investigate the causative genetic defects and especially neoplastic cells often show complex chromosome aberrations and many different marker chromosomes. However, structural homogeneity of the chromosomes in these species as well as less pronounced differences in banding patterns make it difficult to assign genetic abnormalities to certain chromosomes by conventional banding techniques. Here we report for the first time the successful application of multicolor spectral karyotyping (SKY) to rat chromosomes, which allows unequivocal identification of all rat chromosomes with the exception of chromosomes 13 and 14 in different colors, thus enabling the elucidation of even complex rearrangements in the rat karyotype. Flow-sorted chromosome specific painting probes for all 22 rat chromosomes (20 autosomes, X, and Y) were combinatorially labeled by a set of five different fluorochromes and hybridized in situ to metaphase spreads of a healthy rat, to diakineses from testicular material, and to cells from a rat FAO hepatoma cell line. Measuring the complete spectrum at each image point by using the SpectraCube® spectral imaging system and respective computer software allowed identification of the individual rat chromosomes by their specific emission spectra. Classification algorithms in the analysis software can then display the rat chromosomes in specific pseudo-colors and automatically order them in a karyotype table. After its successful application to human and mouse chromosomes, spectral karyotyping of rat chromosomes now also allows cytogenetic screening of the complete rat genome by a single hybridization.
133 new gene localizations on the rabbit cytogenetic map
Authors: Chantry-Darmon C. , Rogel-Gaillard C. , Bertaud M. , Urien C. , Perrocheau M. , Chardon P. , Hayes H.
Published: March 2004

Rabbit (Oryctolagus cuniculus), besides its interest for medical research and biotechnological applications, has a small agronomic production in southern European countries. However, it is still a “map-poor” species with about 80 genes mapped. Recently, useful tools for research on this species have been developed, such as heterologous human-rabbit chromosome painting data and a rabbit BAC library. In this study, our aim is to enrich the rabbit cytogenetic map using the FISH technique. Towards this, we have used cDNAs (rabbit and non rabbit) present in the public databases to determine intra-exon primers used to screen our three-genome equivalent BAC library, by standard PCR directly on DNA pools, and by hybridization of high-density filters. 133 BAC clones containing the genes of interest were isolated and FISH-mapped to the rabbit chromosomes. We present the localization of new genes on all rabbit chromosomes except OCU20 and OCUY and some preliminary data on the rabbit/human comparative map. In addition, this set of BAC clones quite regularly distributed on the rabbit genome will be useful to isolate microsatellites, in order to construct a first generation genetic map.
Safety of Iron Sucrose in Hemodialysis Patients Intolerant to Other Parenteral Iron Products
Authors: Charytan Chaim , Schwenk Michael H. , Al-Saloum Mourhege M. , Spinowitz Bruce S.
Published: March 2004

Background/Aims: This report summarizes the data gathered in four prospective studies of intravenous iron sucrose therapy administered to iron-deficient hemodialysis patients with a history of intolerance to other parenteral iron preparations. Methods: A total of 130 iron dextran- and/or sodium ferric gluconate-sensitive patients received intravenous iron sucrose therapy to correct iron deficiency, and/or maintain body iron stores. A history of intolerance to iron dextran alone was reported in 109 patients, to ferric sodium gluconate alone in 6 patients, and to both iron dextran and ferric sodium gluconate in 15 patients. Therapy with iron sucrose consisted of 100- or 200-mg doses administered undiluted intravenously over 2–5 min, or diluted in normal saline and infused over 15–30 min. Test doses of iron sucrose were not administered. The median cumulative dose was 1,000 mg, with a range of 100–5,000 mg. Results: There were no serious adverse events related to iron sucrose therapy in the 130 patients intolerant to other iron preparations. There were 14 nonserious drug-related adverse events in 8 patients attributed to iron sucrose, none of which resulted in discontinuation of therapy. These events were classified as either of severe (diarrhea), moderate (hypotension, nausea, vomiting), or mild severity (constipation, dry mouth, skin irritation). Conclusion: Iron sucrose therapy is safe and well tolerated in hemodialysis patients intolerant to iron dextran and/or sodium ferric gluconate.
Inhibitors Directed towards Caspase-1 and -3 Are Less Effective than Pan Caspase Inhibition in Preventing Renal Proximal Tubular Cell Apoptosis
Authors: Yang Bin , El Nahas A. Meguid , Fisher Marie , Wagner Bart , Huang Linhong , Storie Ian , Barnett David , Barratt Jonathan , Smith Alice C. , Johnson Timothy S.
Published: March 2004

Background: Uncontrolled apoptosis contributes to tubular cell deletion in renal scarring. Caspase-3 has a central role in the execution of apoptosis and may provide a target for regulating cell death. Here we evaluate three caspase inhibitors: B-D-FMK (pan caspase inhibitor), Z-DEVDFMK (predominantly Caspase-3 inhibitor) and Z-VAD-FMK (predominantly Caspase-1 and -3 inhibitor) to ameliorate apoptosis induced by cisplatin in rat proximal tubular (RPT) cells. Methods: Caspase-3 activity (substrate cleavage assay) and protein (immunocytochemistry and Western blotting), apoptosis (Annexin V flow cytometry, in situend labelling of fragmented DNA, light/electron microscopy and DNA laddering) and cell survival (trypan blue exclusion and propidium iodide flow cytometry) were determined in RPT cells exposed to cisplatin with and without caspase inhibitors. Results: Cisplatin induced a dose-dependent increase in Caspase-3 activity and 8-fold of increase in apoptosis (p < 0.01) when applied for 24 h at 100 µM. B-D-FMK (40 µM), Z-DEVD-FMK (15 µM) and Z-VAD-FMK (22 µM) almost completely inhibited the 25-fold increase in Caspase-3 activity and decreased apoptosis from 15.9 ± 4.4 to 2.0 ± 0.6% (p < 0.01), 15.0 ± 2.2 and 15.0 ± 2.2% respectively. DNA ladders were visible in cisplatin-treated cells, which disappeared following addition of B-D-FMK and decreased with Z-VAD-FMK and Z-DEVD-FMK. Cisplatin reduced cell survival to 61% by trypan blue exclusion. B-D-FMK and Z-VAD-FMK increased this to 87 and 75%, but Z-DEVD-FMK had no significant effect. Conclusions: Cisplatin causes an increase in RPT apoptosis that is associated with increased Caspase-3 activity. All caspase inhibitors were equally effective at reducing Caspase-3 activity, however the pan caspase inhibitor B-D-FMK was more effective at preventing apoptosis and increasing cell survival. Therefore, pan caspase inhibition offers the greatest potential for the prevention of renal tubular cell deletion by uncontrolled apoptosis.
Epithelial Sodium Channel: A Ligand-Gated Channel?
Authors: Horisberger Jean-Daniel , Chraïbi Ahmed
Published: March 2004

The epithelial sodium channel (ENaC) is a key component of the transepithelial Na+ transport. In epithelia, it is responsible for the maintenance of Na+ balance (which in turn controls extracellular fluid volume and arterial blood pressure) and the regulation of airway surface fluid. While the regulation of channel synthesis and surface density have been well described, the control of channel opening is still poorly understood. The channel has a large extracellular domain of as yet unknown function; a number of extracellular factors have been shown to modulate ENaC activity, including extracellular Na+ itself (through a phenomenon called ‘self-inhibition’), several other organic or inorganic cations, which seem to interfere with self-inhibition, and serine proteases. Although a direct interaction with the extracellular domain of ENaC has not yet been demonstrated for each of these modulators, the available data strongly suggest that ENaC behaves as a ligand-gated channel similar to several other members of the ENaC/degenerin family.
A Forskolin Derivative, Colforsin Daropate Hydrochloride, Inhibits the Decrease in Cortical Renal Blood Flow Induced by Noradrenaline or Angiotensin II in Anesthetized Rats
Authors: Ogata Junichi , Minami Kouichiro , Segawa Kayoko , Uezono Yasuhito , Shiraishi Munehiro , Yamamoto Chikako , Sata Takeyoshi , Sung-Teh Kim , Shigematsu Akio
Published: March 2004

A forskolin derivative, colforsin daropate hydrochloride (CDH), acts directly on adenylate cyclase to increase the intracellular cyclic adenosine monophosphate levels which produce a positive inotropic effect and a lower blood pressure. However, little is known about the effects of CDH on the renal function. We used laser Doppler flowmetry to measure the cortical renal blood flow (RBF) in male Wistar rats given a continuous intravenous infusion of CDH and evaluated the effects of CDH on the noradrenaline (NA) and angiotensin II (AngII) induced increases in blood pressure and reductions in RBF. Continuous intravenous administration of CDH at 0.25 µg/kg/min did not affect the mean arterial pressure (MAP), but increased heart rate and RBF. Continuous intravenous administration of CDH at high doses (0.5–0.75 µg/kg/min) decreased the MAP, with little effect on the RBF. The administration of exogenous NA (1.7 µg/kg) increased the MAP and decreased the RBF. However, a bolus injection of NA did not decrease the RBF during continuous intravenous administration of CDH, and CDH did not affect the NA-induced increase in MAP. The administration of exogenous AngII (100 ng/kg) increased MAP and decreased RBF and heart rate, but a bolus injection of AngII did not decrease RBF during continuous intravenous administration of CDH. These results suggest that CDH plays a protective role against the pressor effects and the decrease in RBF induced by NA or AngII.
Endocrinological Effects of High-Dose Hypericum perforatum Extract WS 5570 in Healthy Subjects
Authors: Schüle C. , Baghai T. , Sauer N. , Laakmann G.
Published: March 2004

In this single-blind study, the effects of acute oral administration of high-dose Hypericum perforatum extract WS 5570 on the cortisol (COR), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL) secretions were examined in 12 healthy male volunteers. In a randomized order, the subjects received placebo or WS 5570 at several dosages (600, 900, and 1,200 mg) at 08.00 h on 4 different days. After insertion of an intravenous catheter, blood samples were drawn 1 h prior to administration of placebo or WS 5570 (600, 900, or 1,200 mg), at the time of administration, and during 5 h thereafter at intervals of 30 min. The serum concentrations of COR, GH, and PRL as well as the plasma levels of ACTH were determined in each blood sample by means of double antibody radioimmunoassay, fluoroimmunoassay, and chemiluminescence immunometric assay methods. The area under the curve value was used as parameter for COR, ACTH, GH, and PRL responses. Repeated-measures Anova revealed a significant stimulatory effect of WS 5570 on the ACTH secretion, whereas COR and PRL secretions were not significantly influenced. Moreover, there was a stimulatory peak of GH release 240 min after challenge with WS 5570 in some but not all volunteers, without reaching statistical significance in comparison with placebo. Mean arterial blood pressure and heart rate remained unchanged after administration of WS 5570. Apparently, WS 5570 at the dosages given in this study inconsistently causes endocrinological effects in healthy subjects by influencing central neurotransmitters.
Pituitary-Thyroid State Correlates with Central Dopaminergic and Serotonergic Activity in Healthy Humans
Authors: Strawn J.R. , Ekhator N.N. , D’Souza B.B. , Geracioti Jr. T.D.Geracioti, Jr.
Published: March 2004

Data from lower animals suggest anatomic and physiological interactions between brain dopamine and serotonin (5-hydroxytryptamine, 5-HT) systems and the hypothalamic-pituitary-thyroid axis. However, in humans, investigations of interactions between these central neurochemical systems (especially the dopaminergic system) and thyroid function are rare; in healthy humans they are practically nonexistent. Using cerebrospinal fluid (CSF) and blood samples simultaneously obtained from indwelling subarachnoid and venous catheters in healthy humans, we determined the CSF concentrations of homovanillic acid (HVA) and 5-hydroxyindolacetic acid, the major metabolites of dopamine and 5-HT, and plasma concentrations of TSH, total triiodothyronine (T3), free T3, total thyroxine (T4) and free T4. CSF HVA concentrations were significantly and negatively correlated with plasma TSH and T3 (free and total), but not with T4 (free or total). CSF 5-HIAA concentrations were significantly and negatively correlated with plasma TSH and total T3 but not with free T3 or T4 (free or total). These results indicate that CNS monoamine-thyroid interactions are of physiological significance in the normal, euthyroid human.
Attentional Modulation of Prepulse Inhibition: A New Startle Paradigm
Authors: Heekeren Karsten , Meincke Ulrich , Geyer Mark A. , Gouzoulis-Mayfrank Euphrosyne
Published: March 2004

There is increasing evidence for an influence of directed attention on prepulse inhibition (PPI) of the acoustic startle reflex. However, the existing paradigms for the assessment of this effect have methodological problems and pitfalls. In particular, most previous studies used a paradigm which directed the attention of subjects to the prepulse only. In the present study, we used a modified paradigm which directed the attention of the subjects both to the prepulse and the pulse. Twenty healthy male subjects were instructed trial by trial either to relax or to attend to the startle stimulus and decide whether it was a ‘simple’ (prepulse alone or pulse alone) or a ‘composite’ trial (pulse plus a prepulse or postpulse). Directed attention enhanced PPI at the lead interval of 240 ms, but not at the lead interval of 100 ms. This finding is in line with the idea that attention contributes to PPI when there is enough time for the attentional mechanisms to exert an influence. This new paradigm offers a valuable tool for the study of attentional modulation of sensorimotor gating in humans.
Electroencephalographic Power and Coherence Analyses Suggest Altered Brain Function in Abstinent Male Heroin-Dependent Patients
Authors: Franken Ingmar H.A. , Stam Cornelis J. , Hendriks Vincent M. , van den Brink Wim
Published: March 2004

Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic (EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In the present study, we compared EEG power and coherence measures of 18 abstinent heroin-dependent subjects with those of 12 healthy control subjects. Furthermore, within the heroin group, associations between heroin use in the past, heroin craving and these EEG measures were studied. The results show that heroin-dependent subjects have increased relative beta-2 power and increased left intrahemispheric gamma coherence compared with control subjects. Furthermore, coherence measures showed correlations with clinical variables. These EEG abnormalities may reflect underlying changes in brain function due to long-term drug abuse and premorbid characteristics.
Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke (MATCH): Study Design and Baseline Data
Authors: Diener Hans-Christoph , Bogousslavsky Julien , Brass Lawrence M. , Cimminiello Claudio , Csiba Laszlo , Kaste Markku , Leys Didier , Matias-Guiu Jordi , Rupprecht Hans-Jürgen
Published: March 2004

Background: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. Methods: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. Results: Enrolment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. Conclusion: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.
The Heart in Wegener’s Granulomatosis
Authors: Korantzopoulos Panagiotis , Papaioannides Dimitrios , Siogas Konstantinos
Published: March 2004

Wegener’s granulomatosis (WG) is a necrotizing vasculitis that mainly affects the respiratory tract and kidneys. Of note, involvement of the heart is being increasingly recognized in these patients. Cardiac manifestations can arise from the coronary arteries, pericardium, myocardium, endocardium, valves, conduction system and great vessels, but in most cases cardiac involvement is clinically silent. Consequently, a regular cardiovascular evaluation, including echocardiography, should be performed in every patient with WG, while patients with WG flare should be closely monitored for cardiac complications even in the absence of specific symptoms.
Review of Catheter Thrombectomy Devices
Authors: Suarez Jose A. , Meyerrose Gary E. , Phisitkul Sorot , Kennedy Shalyn , Roongsritong Chanwit , Tsikouris James , Huang Shoei K. Stephen
Published: March 2004

Acute massive pulmonary embolism (PE) is a frequently fatal event that causes significant compromise of hemodynamic stability. Unfortunately, mortality rates for PE have remained relatively constant despite advances in prophylactic and treatment measures. In addition to embolus size, symptom recognition for diagnosis and emergent treatment are two distinct factors that dictate survival. Treatment generally includes thrombolytic agents; however, not all patients are candidates for aggressive thrombolytic management. Development of catheter thrombectomy devices provides an alternative treatment modality for severe cases when thrombolytics are contraindicated. Catheter thrombectomy devices have undergone major advances over the last decade, but literature support of their success is limited.
Prognostic Value of INR Fluctuations during Anticoagulant Therapy in Patients with Atrial Fibrillation and a High Thromboembolic Risk
Authors: Sanchez-Peña Paola , Bouzamondo Anissa , Lechat Philippe
Published: March 2004

Background: Anticoagulation therapy with vitamin K agents needs regular monitoring to maintain the International Normalized Ratio (INR) within the recommended target range (2–3) for an appropriate benefit to risk ratio in patients with atrial fibrillation. Still, INR fluctuates greatly with time, even with the same dose for a given patient. Objective: The purpose of our analysis was to try to identify the possible factors participating in INR fluctuations and to study whether INR instability affects the occurrence of thromboembolic and hemorrhagic events in clinical practice. Methods: We studied INR data of 157 patients participating in a prospective anticoagulant (fluindione) and aspirin association in patients with high-risk atrial fibrillation trial [Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontane (FFAACS) study]. During the first year of follow-up, INR variability was assessed by four different parameters. Logistic regression models were performed to assess the predictive power of INR variability recorded during the first year and its relationship with the occurrence of thromboem bolic and bleeding events during the 5 years of follow- up. Results: No clinical or biological parameter studied was significantly associated with INR variability in this population. No INR variability parameter was significantly predictive of thromboembolic events. In contrast, patients with greater difference between the maximal and the minimal registered INR values and INR variability over time had a significantly higher incidence of any hemorrhagic complication (odds ratios of 2.6 and 1.9, respectively) during follow-up. Conclusions: Large fluctuations of the INR are an important factor to take into account for the bleeding risk in patients with atrial fibrillation with a high thromboembolic risk receiving oral anticoagulation therapy.
Lipid-Soluble Antioxidants and Pregnancy: Maternal Serum Levels of Coenzyme Q10, α-Tocopherol and γ-Tocopherol in Preeclampsia and Normal Pregnancy
Authors: Palan Prabhudas R. , Shaban Danny W. , Martino Teresa , Mikhail Magdy S.
Published: March 2004

It has been hypothesized that in preeclampsia, the antioxidant-deficient state may facilitate increased attacks of free radicals, which may result in endothelial cell damage. The purpose of this study was to investigate the association of three lipid-soluble antioxidants, coenzyme Q10, α-tocopherol and γ-tocopherol, with preeclampsia and normal pregnancy. Serum levels of all three antioxidants in 42 women with normal pregnancies, 25 with mild preeclampsia and 28 with severe preeclampsia were measured by high-pressure liquid chromatography. A significant decrease was observed in serum levels of coenzyme Q10 and α-tocopherol (p < 0.001 for each by the Kruskal-Wallis rank test) in women with preeclampsia compared to levels in normal pregnancy. γ-Tocopherol levels were comparable among the different groups. Logistic regression analysis revealed significant association between grades of preeclampsia and both serum coenzyme Q10 and α-tocopherol levels (p = 0.000 and 0.030, respectively). Coenzyme Q10 and α-tocopherol are potent antioxidants, and the decreased levels of these two antioxidants in preeclampsia may alter the normal redox balance, thereby reducing the ability of antioxidant defenses to protect against free radical damage. This could be a factor in the endothelial cell damage observed in preeclampsia.
Progression in Lacunar Stroke Is Related to Elevated Acute Phase Parameters
Authors: Audebert Heinrich J. , Pellkofer Tina S. , Wimmer Martin L. , Haberl Roman L.
Published: March 2004

Background and Purpose: Despite the small size of lacunar infarcts, progression of neurological deficits is a common problem in this stroke subtype. This investigation studied the frequency and the course of neurological deterioration as well as predictors and possible underlying pathomechanisms of early progression in lacunar stroke. Methods: Fourty-six consecutive patients with acute lacunar stroke were prospectively evaluated by daily clinical neurological examination including the National Institutes of Health Stroke Scale (NIHSS) and follow-up using the Barthel Index after 3 months. Progressive neurological deficit was defined as worsening by ≧1 point in the NIHSS for motor function. Progressive and stable patients were compared regarding clinical profile, inflammatory parameters (leukocytes, body temperature, C-reactive protein), coagulation parameters (fibrinogen, D-dimer, vWF, PTT), and glutamate plasma concentration, as well as blood glucose and blood pressure. Results: Eleven patients (23.9%) showed progression of stroke symptoms, 9 of these within the first 24 h after admission. The score on the NIHSS on admission was similar in patients with progressive stroke and stable patients, but significantly higher in the progressive stroke group on days 2 (p = 0.01), 3 (p = 0.001) and at discharge (p = 0.003). Deterioration was significantly associated with a higher leukocyte count (p = 0.012), higher body temperature (p = 0.031) and a higher fibrinogen concentration (p = 0.046) on admission. Barthel Index at discharge (p = 0.001) and after 90 days (p < 0.001) was significantly worse in the progressive stroke group. Conclusions: Progression in lacunar stroke usually occurs within 24 h and may be related to an acute-phase response. The long-term prognosis of progressive stroke patients is persistently worse compared with patients with nonprogressive stroke.
Overview of Neuropathological Theories of Schizophrenia: From Degeneration to Progressive Developmental Disorder
Authors: de Haan L. , Bakker J.M.
Published: March 2004

Based on a review of literature three main hypotheses on the neuropathology of schizophrenia are identified: (1) neurodegeneration, (2) a disorder that is limited to the early development of the brain, and (3) a progressive developmental disorder. Research findings and clinical observations present evidence that the neurodegeneration hypothesis can be considered inaccurate; they also present several arguments against a disorder that is confined to early development. They are compatible, however, with a progressive developmental disorder. The hypothesis that schizophrenia is a disorder of developmentally reduced synaptic connectivity can account for important aspects of schizophrenia and gives an argument for further research into the possibilities and results of early treatment and perhaps even treatment prior to the first psychotic episode.
Neurocognitive Models of Schizophrenia: A Neurophenomenological Critique
Authors: Gallagher Shaun
Published: March 2004

This paper argues that Frith’s (1992) account of the positive symptoms of schizophrenia in terms of a disruption of metarepresentational self-monitoring is inadequate in several specific ways. More generally, this paper argues against top-down explanations for the loss of the sense of agency in such symptoms. In addition, even if delusions of control might be explained by problems involved in motor control mechanisms involving efference copy and comparators, there are good reasons why the same model cannot explain thought insertion. In place of such neurocognitive explanations, the author develops a neurophenomenological explanation for the loss of the sense of agency and the misattribution of actions and thoughts to others in such symptoms.
Effects of Western, Vegetarian, and Japanese Dietary Fat Model Diets with or without Green Tea Extract on the Plasma Lipids and Glucose, and Liver Lipids in Mice
Authors: Shirai Nobuya , Suzuki Hiramitsu
Published: March 2004

Background/Aims: The purpose of this study was to investigate the long-term effects of three model diets containing different fats, with or without a small amount of green tea extract (GTE), on plasma lipids and glucose, and liver lipids in mice. Methods: Male mice (2 months old) fed 10% fat diets with Western (W), Vegetarian (V), and Japanese (J) fat compositions with or without 0.03% GTE for 7 months. Results: The concentrations of plasma and liver total cholesterol in animals fed the W diet were not significantly different from those fed the J diet. Plasma triacylglycerol (TG) concentrations were significantly different from one another in the following order: V > J > W diet groups. GTE supplementation significantly reduced plasma and liver TG content only in V diet group. Plasma glucose (Glu) concentrations were in the following order: W > V > J diet groups, and the GTE supplementation reduced the concentration of Glu in each diet group. The ratios of plasma n–6 to n–3 fatty acids were in the following order: V > W > J diet groups, regardless of GTE supplementation. Conclusion: These findings show the possibility that Japanese eating habits combined with drinking green tea might be a factor in preventing the onset of non-insulin-dependent diabetes mellitus.
Creutzfeldt-Jakob Disease in Ireland: Epidemiological Aspects 1980–2002
Authors: Horan Gail , Keohane Catherine , Molloy Sophie , Howley Rachel , Harney Michael , Heffernan Josephine , McGuigan Christopher , Hutchinson Michael , Brett Francesca , Farrell Michael
Published: March 2004

Surveillance for Creutzfeldt-Jakob disease (CJD) has been carried out in the Republic of Ireland since 1980. Initial surveillance was passive and based on consented autopsy confirmation of CJD in patients in whom there was a high index of clinical suspicion. Since 1999, an active surveillance programme involving formal notification of all suspect CJD cases has been in place. The annual mortality rate has increased from 0.34 cases/million in 1980 to 1.27 cases/million in 2001. In all, 29 cases have been pathologically confirmed: 1 had variant CJD (vCJD), 1 had iatrogenic human growth hormone-induced CJD and 1 had fatal insomnia. Sporadic CJD (sCJD) accounted for the remainder. This paper details the change in incidence over 22 years as the surveillance programme in Ireland got under way; the increased incidence is attributed to better case ascertainment, as has occurred in other countries where active surveillance programmes have been established.
Polyunsaturated Fatty Acid Plasma Content in Groups of General Population with LowVitamin B6 or Low Iron Serum Levels
Authors: Krajčovičová-Kudláčková M. , Klvanová J. , Dušinská M.
Published: March 2004

Experimental and human studies describe the adverse effect of iron or vitamin B6 deficiencies on polyunsaturated fatty acid metabolism. Iron is present in end proteins of the δ6-desaturase enzyme complex, and vitamin B6 deficiency can affect the transmethylation reaction of proteins. Plasma polyunsaturated fatty acid content was estimated in apparently healthy subjects of the general population with no consumption of fish and low vitamin B6 serum levels (<3 µg/l; n = 21) or with low iron serum levels (men: <12 µmol/l; women: <10 µmol/l; n = 16) and compared to a control group (n = 22) with normal vitamin B6 and iron serum levels (in reference range). The activities of the δ6-desaturase enzyme complex were calculated as product/precursor (conversion indices). In groups of subjects with low vitamin B6 and low iron levels, δ6-desaturase activity together with δ5-desaturase activity (conversion of α-linolenic/18:3,n–3/ into eicosapentaenoic acid/20:5,n–3/) as well as the conversion index of docosahexaenoic acid formation (22:6,n–3) from 22:5,n–3 (second δ6-desaturase activity) were significantly reduced. The inhibition effect on fatty acid synthesis was more pronounced in subjects with low iron levels than in those with low vitamin B6 levels. The conversion indices correlated significantly positively with vitamin B6 or iron levels.
Mitochondrial Abnormalities in Genetically Assessed Oculopharyngeal Muscular Dystrophy
Authors: Gambelli S. , Malandrini A. , Ginanneschi F. , Berti G. , Cardaioli E. , De Stefano R. , Franci M. , Salvadori C. , Mari F. , Bruttini M. , Rossi A. , Federico A. , Renieri A.
Published: March 2004

We report a family with a clinical diagnosis of oculopharyngeal muscular dystrophy in which muscle biopsy showed mitochondrial changes such as cytochrome-c-oxidase-negative fibers and aggregates of mitochondria containing paracrystalline inclusions. Molecular analysis demonstrated a GCG expansion in the poly(A)-binding protein 2 (PABP2) gene and failed to demonstrate multiple deletions of mtDNA. We hypothesize that mitochondrial abnormalities may be a secondary phenomenon. This observation may suggest that the PABP2 gene could interfere in the posttranscriptional regulation of genes involved in mitochondrial function.
Polyamine Synthesis Inhibition Attenuates Vascular Smooth Muscle Cell Migration
Authors: Liang Min , Ekblad Eva , Hellstrand Per , Nilsson Bengt-Olof
Published: March 2004

Vascular smooth muscle cell migration, occurring after intimal injury, is a substantial clinical problem in atherosclerosis and restenosis after stenting. Here we investigate the effects of polyamine synthesis inhibition on vascular smooth muscle cell migration after maximal and submaximal growth stimulation with PDGF-AB or FCS. Vascular smooth muscle cells were obtained from mouse aorta explants. These cells coexpressed smooth muscle α-actin, PDGFRα and PDGFRβ as demonstrated by immunocytochemistry. Treatment with a high (100 ng/ ml) concentration of PDGF-AB stimulated DNA synthesis 6-fold and markedly elevated cell migration. PDGF-AB (100 ng/ml) increased cellular spermidine concentration 2-fold, but had no effect on spermine or putrescine levels. Treatment with the polyamine synthesis inhibitors CGP48664 (1 µM) and DFMO (5 mM) prevented the PDGF-AB-induced increase in spermidine and reduced spermine concentrations, but had no effect on PDGF-AB-stimulated DNA synthesis or cell migration. Cell migration after submaximal stimulation with either PDGF-AB (8 ng/ml) or FCS (8%) was, however, inhibited by the polyamine synthesis blockers. In summary, these data show that polyamine synthesis inhibition attenuates vascular smooth muscle cell migration under submaximal growth-stimulating conditions, suggesting that polyamines participate in regulation of cell migration and that treatment with polyamine synthesis inhibitors might reduce vascular smooth muscle cell migration after intimal injury.
CXCL16/SR-PSOX Is an Interferon-γ–Regulated Chemokine and Scavenger Receptor Expressed in Atherosclerotic Lesions
Authors: Wuttge Dirk M. , Zhou Xinghua , Sheikine Yuri , Wågsäter Dick , Stemme Veronika , Hedin Ulf , Stemme Sten , Hansson Göran K. , Sirsjö Allan
Published: March 2004

Objective—

Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-γ (IFN-γ)-cytokine abundant in atherosclerotic lesions.

Methods and Results—

CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E–deficient mice. In vitro IFN-γ induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN-γ induced CXCL16 expression in murine atherosclerotic lesions.

Conclusions—

We demonstrate a novel role of IFN-γ in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.
Rapid Perfusion and Network Remodeling in a Microvascular Construct After Implantation
Authors: Shepherd Benjamin R. , Chen Helen Y.S. , Smith Cynthia M. , Gruionu Gabriel , Williams Stuart K. , Hoying James B.
Published: March 2004

Objective—

We have previously demonstrated the ability to construct 3-dimensional microvascular beds in vitro via angiogenesis from isolated, intact, microvessel fragments that retain endothelial cells and perivascular cells. Our objective was to develop and characterize an experimental model of tissue vascularization, based on the implantation of this microvascular construct, which recapitulated angiogenesis, vessel differentiation, and network maturation.

Methods and Results—

On implantation in a severe combined-immunodeficient mouse model, vessels in the microvascular constructs rapidly inosculated with the recipient host circulation. Ink perfusion of implants via the left ventricle of the host demonstrated that vessel inosculation begins within the first day after implantation. Evaluation of explanted constructs over the course of 28 days revealed the presence of a mature functional microvascular bed. Using a probe specific for the original microvessel source, 91.7%±11% and 88.6%±19% of the vessels by day 5 and day 28 after implantation, respectively, were derived from the original microvessel isolate. Similar results were obtained when human-derived microvessels were used to build the microvascular construct.

Conclusions—

With this model, we reproduce the important aspects of vascularization, angiogenesis, inosculation, and network remodeling. Furthermore, we demonstrate that the model accommodates human-derived vessel fragments, enabling the construction of human-mouse vascular chimeras.
Increase of Circulating Endothelial Progenitor Cells in Patients with Coronary Artery Disease After Exercise-Induced Ischemia
Authors: Adams Volker , Lenk Karsten , Linke Axel , Lenz Dominik , Erbs Sandra , Sandri Markus , Tarnok Attila , Gielen Stephan , Emmrich Frank , Schuler Gerhard , Hambrecht Rainer
Published: March 2004

Objectives—

The concept of neovascularization in response to tissue ischemia has been extended by the finding of postnatal vasculogenesis initiated by endothelial progenitor cells (EPCs). The aim of this study was to analyze whether a maximal stress test in patients with coronary artery disease (CAD) increases the number of circulating EPCs.

Methods and Results—

Blood concentration of EPCs was analyzed by FACS and cell culture assay in CAD patients with (n=16) or without (n=12) exercise-induced myocardial ischemia and in healthy subjects (n=11) for up to 144 hours after maximal stress test. Plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, tumor necrosis factor-α, and granulocyte macrophage-colony stimulating factor were determined by ELISA. EPCs increased significantly in ischemic patients, with a maximum after 24 to 48 hours (cell culture: 3.3±0.5-fold increase; FACS: 3.1±0.6-fold increase) and returned to baseline within 72 hour. In nonischemic patients and healthy subjects, no EPC increase was detectable. VEGF levels in ischemic patients increased significantly after 2 to 6 hours (maximum after 2 hours; 4.0±1.1-fold increase) and no change was observed in nonischemic patients and healthy subjects; ΔVEGF and ΔEPC correlated significantly (
r
=0.66).

Conclusions—

Patients with symptomatic CAD respond to a single episode of exercise-induced myocardial ischemia with a time-dependent increase in circulating EPCs. This increase may be related to and preceded by an increase in plasma VEGF.
Imatinib Attenuates Diabetes-Associated Atherosclerosis
Authors: Lassila Markus , Allen Terri J. , Cao Zemin , Thallas Vicki , Jandeleit-Dahm Karin A. , Candido Riccardo , Cooper Mark E.
Published: March 2004

Objective—Diabetes is associated with accelerated atherosclerosis, the major factor contributing to increased mortality and morbidity in the diabetic population. The molecular mechanisms by which diabetes promotes atherosclerosis are not fully understood. Platelet-derived growth factor has been shown to play a major role in the pathology of vascular diseases, but whether it plays a role in atherosclerosis associated with diabetes remains unknown. The aims of this study were to assess whether platelet-derived growth factor–dependent pathways are involved in the development of diabetes-induced atherosclerosis and to determine the effects of platelet-derived growth factor receptor antagonism on this disorder.

Methods and Results—Diabetes was induced by injection of streptozotocin in 6-week-old apolipoprotein E knockout mice. Diabetic animals received treatment with a tyrosine kinase inhibitor that inhibits platelet-derived growth factor action, imatinib (STI-571, 10 mg/kg per day), or no treatment for 20 weeks. Nondiabetic apolipoprotein E knockout mice served as controls. Induction of diabetes was associated with a 5-fold increase in plaque area in association with an increase in aortic platelet-derived growth factor-B expression and platelet-derived growth factor-β receptor phosphorylation as well as other prosclerotic and proinflammatory cytokines. Imatinib treatment prevented the development of atherosclerotic lesions and diabetes-induced inflammatory cytokine overexpression in the aorta.

Conclusions—Tyrosine kinase inhibition with imatinib appears to be a novel therapeutic option to retard the development of atherosclerosis, specifically in the context of diabetes.