bluuebunny/crossref_metadata_2025 huggingface dataset:
BANACH SPACE VALUED CAUCHY–RIEMANN EQUATIONS WITH TOTALLY REAL BOUNDARY CONDITIONS
Authors: WEHRHEIM KATRIN
Published: August 2004

The main purpose of this paper is to give a general regularity result for Cauchy–Riemann equations in complex Banach spaces with totally real boundary conditions. The usual elliptic Lp-regularity results hold true under one crucial assumption: The Banach space is isomorphic to a closed subspace of an Lp-space. (Equivalently, the totally real submanifold is modelled on a closed subspace of an Lp-space.)

Secondly, we describe a class of examples of such totally real submanifolds, namely gauge invariant Lagrangian submanifolds in the space of connections over a Riemann surface. These pose natural boundary conditions for the anti-self-duality equation on 4-manifolds with a boundary space-time splitting, leading towards the definition of a Floer homology for 3-manifolds with boundary, which is the first step in a program by Salamon for the proof of the Atiyah–Floer conjecture. The principal part of such a boundary value problem is an example of a Banach space valued Cauchy–Riemann equation with totally real boundary condition.
ON ALGEBRAIC HYPERBOLICITY OF LOG VARIETIES
Authors: CHEN XI
Published: August 2004

Kobayashi conjecture says that every holomorphic map [Formula: see text] is constant for a very general hypersurface D⊂ℙnof degree deg D≥2n+1. As a corollary of our main theorem, we show that f is constant if [Formula: see text] is contained in an algebraic curve.
MULTIPLE SOLUTIONS FOR THE DIRICHLET PROBLEM FOR H-SYSTEMS WITH SMALL H
Authors: ISOBE TAKESHI
Published: August 2004

Let [Formula: see text] be the 2-dimensional unit disk and [Formula: see text]. For suitably small H>0, we consider the Dirichlet problem for H-systems [Formula: see text] It is well-known that (H) admits at least two distinct solutions for non-constant γ and small H>0. In this paper, we introduce conditions on γ and develop methods of finding at least three distinct solutions to (H) under such conditions on γ.
INVERSE TOPOLOGICAL PRESSURE WITH APPLICATIONS TO HOLOMORPHIC DYNAMICS OF SEVERAL COMPLEX VARIABLES
Authors: MIHAILESCU EUGEN , URBAŃSKI MARIUSZ
Published: August 2004

In this paper, we introduce a few notions of inverse topological pressure [Formula: see text], defined in terms of backward orbits (prehistories) instead of forward orbits. This inverse topological pressure has some properties similar to the regular (forward) pressure but, in general, if the map is not a homeomorphism, they do not coincide. In fact, there are several ways to define inverse topological pressure; for instance, we show that the Bowen type definition coincides with the one using spanning sets.

Then we consider the case of a holomorphic map [Formula: see text] which is Axiom A and such that its critical set does not intersect a particular basic set of saddle type Λ.

We will prove that, under a technical condition, the Hausdorff dimension of the intersection between the local stable manifold and the basic set is equal to ts, i.e. [Formula: see text], for all points x belonging to Λ. Here ts represents the unique zero of the function t→P-(tϕs), with P- denoting the inverse topological pressure and [Formula: see text], y∈Λ. In general, [Formula: see text] will be estimated above by ts and below by [Formula: see text], where [Formula: see text] is the unique zero of the map t→P_(tϕs).

As a corollary we obtain that, if the stable dimension is non-zero, then Λ must be a non-Jordan curve, and also, if f|Λ happens to be a homeomorphism (like in the examples from [13]), then the stable dimension cannot be zero.
SMOOTHING EFFECT AND LARGE TIME BEHAVIOR OF SOLUTIONS TO SCHRÖDINGER EQUATIONS WITH NONLINEARITY OF INTEGRAL TYPE
Authors: OZAWA T. , YAMAZAKI Y.
Published: August 2004

We study the smoothing effect in space and asymptotic behavior in time of solutions to the Cauchy problem for the nonlinear Schrödinger equation with interaction described by the integral of the intensity with respect to one direction in two space dimensions. A detailed description is given on the phase modification of scattering solutions by taking into account the long range effect of the interaction.
NON-LINEAR SURFACE SUPERCONDUCTIVITY IN THREE DIMENSIONS IN THE LARGE κ LIMIT
Authors: ALMOG Y.
Published: August 2004

The Ginzburg–Landau model of superconductivity is considered in three dimensions. We show, for smooth bounded domains, that the superconductivity order parameter decays exponentially fast away from the boundary as the Ginzburg–Landau parameter κ tends to infinity. We prove this result for applied magnetic fields satisfying |hex|-κ≫κ1/2. Additionally, we prove that for applied fields greater than HC2, the only solution in ℝ3 satisfying a certain decay condition is the normal state. Finally we prove that bulk superconductivity decreases to zero as |hex|↑HC2, and thus extend (though in a weaker sense), the results in [23] to three-dimensional settings.
CROSSINGLESS MATCHINGS AND THE COHOMOLOGY OF (n, n) SPRINGER VARIETIES
Authors: KHOVANOV MIKHAIL
Published: August 2004

In an earlier paper, the author introduced a collection of rings that control a categorification of the quantum sl(2) invariant of tangles. We prove that centers of these rings are isomorphics to the cohomology rings of the (n, n) Springer varieties and show that the braid group action in the derived category of modules over these rings descends to the Springer action of the symmetric group.
Cardiac glucose utilization in mice with mutated α- and β-thyroid hormone receptors
Authors: Esaki Takanori , Suzuki Hideyo , Cook Michelle , Shimoji Kazuaki , Cheng Sheue-Yann , Sokoloff Louis , Nunez Jacques
Published: August 2004

Abnormal thyroid function is usually associated with altered cardiac function. Mutations in the thyroid hormone (TH)-binding region of the TH β-receptor (TRβ) that eliminate its TH-binding ability lead to the thyroid hormone resistance syndrome (RTH) in humans, which is characterized by high blood TH levels, goiter, hyperactivity, and tachycardia. Mice with “knock-in” mutations in the TH α-receptor (TRα) or TRβ that remove their TH-binding ability have been developed, and those with the mutated TRβ (TRβPV/PV) appear to provide a model for RTH. These two types of mutants show different effects on cerebral energy metabolism, e.g., negligible change in glucose utilization (CMRGlc) in TRβPV/PVmice and markedly reduced CMRGlc, like that found in cretinous rats, in the mice (TRαPV/+) with the knock-in mutation of the TRα gene. Studies in knockout mice have indicated that the TRα may also influence heart rate. Because mutations in both receptor genes appear to affect some parameters of cardiac function and because cardiac functional activity and energy metabolism are linked, we measured heart glucose utilization (HMRGlc) in both the TRβPV/PVand TRαPV/+mutants. Compared with values in normal wild-type mice, HMRGlcwas reduced (−77 to −95%) in TRαPV/+mutants and increased (87 to 340%) in TRβPV/PVmutants, the degree depending on the region of the heart. Thus the TRαPV/+and TRβPV/PVmutations lead, respectively, to opposite effects on energy metabolism in the heart that are consistent with the bradycardia seen in hypothyroidism and the tachycardia associated with hyperthyroidism and RTH.
Hormonal responses to fasting and refeeding in chronic renal failure patients
Authors: Deshmukh Sonali , Phillips Bradley G. , O'Dorisio Thomas , Flanigan Michael J. , Lim Victoria S.
Published: August 2004

To study anorexia in chronic renal failure (CRF) patients, we measured appetite-related hormones in seven CRF patients and four controls. Plasma concentrations and fractional changes from baseline (values from day 1, 0800) are listed as control vs. CRF (means ± SE). Leptin, although higher in CRF (5.6 ± 1.7 and 34 ± 17 ng/ml), was suppressed after fasting; decrements were −51 ± 9 and −55 ± 8%. Nocturnal surge present during feeding was abolished upon fasting in both groups. Neuropeptide Y (NPY) was elevated in CRF (72 ± 12 vs. 304 ± 28 pg/ml, P = 0.0002). NPY rhythm, reciprocal to that of leptin, was muted in CRF. Basal cortisol was similar in both groups (17 ± 3 and 17 ± 2 μg/dl). In the controls, cortisol peaked in the morning and declined in the evening. CRF showed blunted cortisol suppression. Decrements were −61 ± 3 and −20 ± 9% at 1800 on day 1 ( P = 0.008) and −61 ± 8 and −26 ± 8% at 2000 on day 2 ( P = 0.02). Basal ACTH (25 ± 5 and 54 ± 16 pg/ml) as well as diurnal pattern was not statistically different between the groups. Baseline insulin was 6 ± 1 and 20 ± 9 μU/ml. During fasting, insulin was suppressed to −64 ± 10 and −51 ± 9%, respectively. Upon refeeding, increments were 277 ± 96 and 397 ± 75%. Thus, in our CRF patients, anorexia was not due to excess leptin or deficient NPY. Impaired cortisol suppression should favor eating. Insulin suppression during fasting and secretion after feeding should enhance both eating and anabolism. The constant high NPY suggests increased tonic hypersecretion.
Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle
Authors: Fischer Christian P. , Plomgaard Peter , Hansen Anne K. , Pilegaard Henriette , Saltin Bengt , Pedersen Bente Klarlund
Published: August 2004

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.
Effects of dietary fat, NaCl, and fructose on renal sodium and water transporter abundances and systemic blood pressure
Authors: Song Jian , Hu Xinqun , Shi Min , Knepper Mark A. , Ecelbarger Carolyn A.
Published: August 2004

Dietary fructose, NaCl, and/or saturated fat have been correlated with mean arterial pressure (MAP) rises in sensitive strains of rats. Dysregulation of sodium and/or water reabsorption by the kidney may contribute. Using radiotelemetry and parallel semiquantitative immunoblotting, we examined the effects of various diets on MAP and the regulation of abundance of the major renal sodium and water transport proteins in male Sprague-Dawley rats. In study 1, rats (∼275 g) were fed one of four diets for 4 wk ( n = 6/group): 1) control, 2) 65% fructose, 3) control + added NaCl (2.59%), or 4) fructose + NaCl. In study 2, 5% butter (fat) was added to the above four diets. Both fat and NaCl, but not fructose, caused modest rises in MAP (5–10 mmHg) and increased the day-to-night ratio in diastolic blood pressure. NaCl or fructose increased kidney size. Creatinine clearance was increased by salt or fat, and fractional excretion of sodium was decreased by fat. In study 1, high NaCl markedly reduced plasma renin and aldosterone and its regulated proteins in whole kidney, i.e., the thiazide-sensitive Na-Cl cotransporter and the α- and γ (70-kDa band)-subunits of the epithelial sodium channel. These effects were blunted by fat. Fructose increased the abundance of the sodium phosphate cotransporter, whereas it decreased the bumetanide-sensitive Na-K-2Cl cotransporter and aquaporin-2. Overall, doubling of dietary fat appeared to impair dietary sodium adaptation, i.e., blunt the downregulation of aldosterone-mediated effects, thus allowing blood pressure to rise at an accelerated rate.
Adaptation in Thalamic Barreloid and Cortical Barrel Neurons to Periodic Whisker Deflections Varying in Frequency and Velocity
Authors: Khatri V. , Hartings J. A. , Simons D. J.
Published: August 2004

Layer IV circuitry in the rodent whisker-to-barrel pathway transforms the thalamic input signal spatially and temporally. Excitatory and inhibitory barrel neurons display response properties that differ from each other and from their common thalamic inputs. Here we further examine thalamocortical response transformations by characterizing the responses of individual thalamic barreloid neurons and presumed excitatory and inhibitory cortical barrel neurons to periodic whisker deflections varying in frequency from 1 to 40 Hz. Both pulsatile and sinusoidal periodic stimulation of fixed deflection amplitude were used to assess stimulus-evoked adaptation of thalamocortical units (TCUs), fast-spike barrel units (FSUs: presumed inhibitory neurons), and regular-spike barrel units (RSUs: presumed excitatory neurons). Monotonic, frequency-dependent reductions in firing were observed in thalamic and cortical neurons to the second and subsequent stimuli in trains of high (pulsatile)- and low (sinusoidal)-velocity deflections. RSUs and FSUs adapted substantially more than their thalamic input neurons, and at all frequencies, FSUs fired at higher rates than the other two cell types. For example at 40 Hz, response magnitudes of TCUs decreased by 34%, FSUs by 72%, and RSUs by 78%. Across frequencies, RSUs and FSUs displayed more cycle-by-cycle entrainment and phase-locked responses for (high velocity) pulsatile than (lower velocity) sinusoidal deflections; for TCUs, phase-locking was equivalent for both stimuli, but entrainment was higher for sinusoidal deflections. Strong feed-forward inhibition, in conjunction with synaptic depression, renders the firing of barrel neurons sparse but temporally faithful to the occurrence of repetitive whisker deflections, especially when they are of high velocity.
The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans
Authors: Konstantinov Igor E. , Arab Sara , Kharbanda Rajesh K. , Li Jia , Cheung Michael M. H. , Cherepanov Vera , Downey Gregory P. , Liu Peter P. , Cukerman Eva , Coles John G. , Redington Andrew N.
Published: August 2004

Remote ischemic preconditioning (IPC) reduces tissue injury caused by ischemia-reperfusion (IR) in distant organs. We tested the hypothesis that remote IPC (rIPC) modifies inflammatory gene transcription in humans. Using a microarray method, we demonstrated that a simple model of brief forearm ischemia suppresses proinflammatory gene expression in circulating leukocytes. Genes encoding key proteins involved in cytokine synthesis, leukocyte chemotaxis, adhesion and migration, exocytosis, innate immunity signaling pathways, and apoptosis were all suppressed within 15 min (early phase IPC) and more so after 24 h (second window IPC). Changes in leukocyte CD11b expression measured by flow cytometry mirrored this pattern, with there being a significant ( P = 0.01) reduction at 24 h. The results of this study show that the rIPC stimulus modifies leukocyte inflammatory gene expression. This effect may contribute to the protective effect of IPC against IR injury and may have broader implications in other inflammatory processes. This is the first study of human gene expression following rIPC stimulus. rIPC stimulus suppressed proinflammatory gene transcription in human leukocytes.
Identification of genes contributing to the obese yellowAvyphenotype: caloric restriction, genotype, diet × genotype interactions
Authors: Kaput Jim , Klein Karin G. , Reyes Eric J. , Kibbe Warren A. , Cooney Craig A. , Jovanovic Borko , Visek Willard J. , Wolff George L.
Published: August 2004

The incidence and severity of obesity and type 2 diabetes are increasing in Western societies. The progression of obesity to type 2 diabetes is gradual with overlapping symptoms of insulin resistance, hyperinsulinemia, hyperglycemia, dyslipidemias, ion imbalance, and inflammation; this complex syndrome has been called diabesity. We describe here comparisons of gene expression in livers of A/ a (agouti) vs. Avy/ A (obese yellow) segregants (i.e., littermates) from BALB/cStCrlfC3H/Nctr × VYWffC3Hf/Nctr- Avy/ a matings in response to 70% and 100% of ad libitum caloric intakes of a reproducible diet. Twenty-eight ( 28 ) genes regulated by diet, genotype, or diet × genotype interactions mapped to diabesity quantitative trait loci. A subset of the identified genes is linked to abnormal physiological signs observed in obesity and diabetes.
Na+/H+exchanger 1 deficiency alters gene expression in mouse brain
Authors: Zhou Dan , Xue Jin , Gavrialov Orit , Haddad Gabriel G.
Published: August 2004

Na+/H+exchanger 1 (NHE1) is well known to function as a major regulator of intracellular pH (pHi). It is activated by low pHiand exchanges extracellular Na+for intracellular H+to maintain cellular homeostasis. Despite the fact that we now have evidence suggesting other roles for NHE1, there has been no comprehensive study investigating its role as a signaling molecule. Toward this aim, we used in this study NHE1 null mutant mice and cDNA microarrays to investigate the effects of NHE1 on global gene expression in various regions of the brain, e.g., cortex, hippocampus, brain stem-diencephalon, and cerebellum. We found that a total of 35 to 79 genes were up- or downregulated in each brain region, with the majority being downregulated. The effect of NHE1 null mutation on gene expression is region specific, and only 11 genes were changed in all brain regions studied. Further analysis of the cis-regulatory regions of downregulated genes revealed that transcription suppressors, BCL6 and E4BP4, were probable candidates that mediated the inhibitory effect of NHE1 null mutation. One of the genes, MCT-13, was not only downregulated in the NHE1 null mutant brain but also in tissue cultures treated with an NHE1 inhibitor. We conclude that 1) a relatively small number of genes were altered in the NHE1 null mouse brain; 2) the effects of NHE1 null mutation on gene expression are region specific; and 3) several genes implicated in neurodegeneration have altered expression, potentially offering a molecular explanation for the phenotype of the NHE1 null mouse.
Identification and regulation of Sprouty1, a negative inhibitor of the ERK cascade, in the human heart
Authors: Huebert Robert C. , Li Qinglu , Adhikari Neeta , Charles Nathan J. , Han Xinqiang , Ezzat Mohammed-Karim , Grindle Suzanne , Park Soon , Ormaza Sofia , Fermin David , Miller Leslie W. , Hall Jennifer L.
Published: August 2004

We screened a compendium of gene profiles from 19 paired human heart samples harvested at the time of implant and explant of a left ventricular assist device (LVAD) for novel genes regulating the Ras/MEK/ERK cascade. From this analysis we identified Sprouty1, an evolutionally conserved gene that acts as an intrinsic inhibitor of the Ras/MEK/ERK pathway. Sprouty1 mRNA and protein were significantly upregulated in the heart in response to mechanical unloading with a LVAD. The upregulation of Sprouty1 in the heart following mechanical unloading was accompanied by a significant decrease in phosphorylated ERK1/2. Gain of function experiments demonstrated that upregulation of Sprouty1 in isolated cardiac myocytes led to a significant decrease and altered kinetics of ERK1/2 phosphorylation. Immunohistochemistry of human hearts revealed that Sprouty1 was also expressed in the microvasculature. Upregulation of Sprouty1 in endothelial cells led to a significant decrease in VEGF-induced endothelial cell proliferation. To our knowledge, these findings are the first to define Sprouty expression in the heart and suggest that Sprouty1 may serve as an intrinsic mediator governing ventricular remodeling through a coordinated coupling of both myocyte and vascular alterations in response to mechanical load.
Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy
Authors: Chen Hua , Huang Xueyin N. , Stewart Alexandre F. R. , Sepulveda Jorge L.
Published: August 2004

Fibronectin (FN) is an extracellular matrix protein that binds to integrin receptors and couples cardiac myocytes to the basal lamina. Cardiac FN expression is elevated in models of pressure overload, and FN causes cultured cardiac myocytes to hypertrophy by a mechanism that has not been characterized in detail. In this study, we analyzed the gene expression changes induced by FN in purified rat neonatal ventricular myocytes using the Affymetrix RAE230A microarray, to understand how FN affects gene expression in cardiac myocytes and to separate the effects contributed by cardiac nonmyocytes in vivo. Pathway analysis using z-score statistics and comparison with a mouse model of cardiac hypertrophy revealed several pathways stimulated by FN in cardiac myocytes. In addition to the known cardiac myocyte hypertrophy markers, FN significantly induced metabolic pathways including virtually all of the enzymes of cholesterol biosynthesis, fatty acid biosynthesis, and the mitochondrial electron transport chain. FN also increased the expression of genes coding for ribosomal proteins, translation factors, and the ubiquitin-proteasome pathway. Interestingly, cardiac myocytes plated on FN showed elevated expression of the fibrosis-promoting peptides connective tissue growth factor (CTGF), WNT1 inducible signaling pathway protein 2 (WISP2), and secreted acidic cysteine-rich glycoprotein (SPARC). Our data complement in vivo studies and reveal several novel genes and pathways stimulated by FN, pointing to cardiac myocyte-specific mechanisms that lead to development of the hypertrophic phenotype.
A γGT-AT1Areceptor transgene protects renal cortical structure in AT1receptor-deficient mice
Authors: Le Thu H. , Oliverio Michael I. , Kim Hyung-Suk , Salzler Harmony , Dash Rajesh C. , Howell David N. , Smithies Oliver , Bronson Sarah , Coffman Thomas M.
Published: August 2004

To understand the physiological role of angiotensin type 1 (AT1) receptors in the proximal tubule of the kidney, we generated a transgenic mouse line in which the major murine AT1receptor isoform, AT1A, was expressed under the control of the P1 portion of the γ-glutamyl transpeptidase (γGT) promoter. In transgenic mice, this promoter has been shown to confer cell-specific expression in epithelial cells of the renal proximal tubule. To avoid random integration of multiple copies of the transgene, we used gene targeting to produce mice with a single-copy transgene insertion at the hypoxanthine phosphoribosyl transferase ( Hprt) locus on the X chromosome. The physiological effects of the γGT-AT1Atransgene were examined on a wild-type background and in mice with targeted disruption of one or both of the murine AT1receptor genes ( Agtr1a and Agtr1b). On all three backgrounds, γGT-AT1Atransgenic mice were healthy and viable. On the wild-type background, the presence of the transgene did not affect development, blood pressure, or kidney structure. Despite relatively low levels of expression in the proximal tubule, the transgene blunted the increase in renin expression typically seen in AT1-deficient mice and partially rescued the kidney phenotype associated with Agtr1a−/−Agtr1b−/−mice, significantly reducing cortical cyst formation by more than threefold. However, these low levels of cell-specific expression of AT1receptors in the renal proximal tubule did not increase the low blood pressures or abolish sodium sensitivity, which are characteristic of AT1receptor-deficient mice. Although our studies do not clearly identify a role for AT1receptors in the proximal tubules of the kidney in blood pressure homeostasis, they support a major role for these receptors in modulating renin expression and in maintaining structural integrity of the renal cortex.
A unifying statistical model for QTL mapping of genotype × sex interaction for developmental trajectories
Authors: Zhao Wei , Ma Changxing , Cheverud James M. , Wu Rongling
Published: August 2004

Most organisms display remarkable differences in morphological, anatomical, and developmental features between the two sexes. It has been recognized that these sex-dependent differences are controlled by an array of specific genetic factors, mediated through various environmental stimuli. In this paper, we present a unifying statistical model for mapping quantitative trait loci (QTL) that are responsible for sexual differences in growth trajectories during ontogenetic development. This model is derived within the maximum likelihood context, incorporated by sex-stimulated differentiation in growth form that is described by mathematical functions. A typical structural model is implemented to approximate time-dependent covariance matrices for longitudinal traits. This model allows for a number of biologically meaningful hypothesis tests regarding the effects of QTL on overall growth trajectories or particular stages of development. It is particularly powerful to test whether and how the genetic effects of QTL are expressed differently in different sexual backgrounds. Our model has been employed to map QTL affecting body mass growth trajectories in both male and female mice of an F2population derived from the large (LG/J) and small (SM/J) mouse strains. We detected four growth QTL on chromosomes 6, 7, 11, and 15, two of which trigger different effects on growth curves between the two sexes. All the four QTL display significant genotype-sex interaction effects on the timing of maximal growth rate in the ontogenetic growth of mice. The implications of our model for studying the genetic architecture of growth trajectories and its extensions to some more general situations are discussed.
Molecular diversity of cardiac endothelial cells in vitro and in vivo
Authors: Hendrickx Jan , Doggen Kris , Weinberg Ellen O. , Van Tongelen Pascale , Fransen Paul , De Keulenaer Gilles W.
Published: August 2004

In addition to a number of common features, cardiovascular endothelium displays structural, functional, and genetic differences according to its position in the cardiovascular tree. In the heart, endocardial and cardiac microvascular endothelia (CMVE) interact directly with surrounding cardiomyocytes, whereas the endothelium within blood vessels interacts with smooth muscle cells. In this study, we investigated whether cardiac endothelial cells were distinct from aortic endothelial (AE) cells at the transcriptional level. Using Affymetrix microarray technology and subsequent real-time PCR analyses for validation, we identified sets of genes with marked preferential expression in cultured endocardial endothelium (EE) compared with cultured AE and vice versa. Among the genes preferentially expressed in EE, some were also expressed in cultured CMVE. Immunohistochemical staining of cardiac and aortic tissue revealed that the endothelial genetic diversity observed in culture reflects, in part, a physiological diversity existing in vivo. The identification of a set of genes preferentially expressed in EE provides new insights in the functional adaptations of this endothelial subtype to its intracavitary localization and to its role in the control of ventricular performance.
Efficacy of Donepezil Treatment in Alzheimer Patients with and without Subcortical Vascular Lesions
Authors: Blasko Imrich , Bodner Thomas , Knaus Gabriele , Walch Thomas , Monsch Andreas , Hinterhuber Hartmann , Marksteiner Josef
Published: August 2004

In a pilot study designed as a case control study the efficacy of donepezil treatment was investigated in patients with Alzheimer’s disease (AD). Patients were stratified according to radiological criteria into patients without (AD group) and with subcortical vascular lesions (AD+SVD group). Changes in cognition were assessed as the primary outcome measurement after 6 and 18 months of treatment by the Mini-Mental Status Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery. After 6 months, patients had improved from baseline by 0.7 points in MMSE score in the AD group and by 1.8 in the AD+SVD group. After 18 months of treatment, the AD+SVD group performed significantly worse in one CERAD subscore, whereas a deterioration in two subscores was observed in the AD group. A comparison between the 2 groups revealed that treatment did not lead to statistically significant differences between the AD and AD+SVD groups in any of CERAD parameters following 6 or 18 months of treatment. These data support previous observations that donepezil therapy is effective in AD patients with and without subcortical vascular lesions.
Roxithromycin Suppresses Mucin Gene Expression in Epithelial Cells
Authors: Kim Dong-Young , Takeuchi Kazuhiko , Ishinaga Hajime , Kishioka Chikako , Suzuki Shinya , Basbaum Carol , Majima Yuichi
Published: August 2004

Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D4 (LTD4) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD4 > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-ĸB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-ĸB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-ĸB activation.
Lachrymal Determinations: Methods and Updates on Biopharmaceutical and Clinical Applications
Authors: Dumortier G. , Chaumeil J.C.
Published: August 2004

This article displays different procedures used to collect lachrymal fluid and describes some of its applications. Sampling tears represents the main difficulty to produce precise and reproducible results. The direct sampling procedure consists in collecting tears with capillary tubes and has the drawback of demanding previous stimulation that induces major dilution. The indirect method does not require preliminary stimulation but has been held responsible for altering epithelium and promoting leakage from plasma. Schirmer strips and sponges are classically required. Applications are numerous in biopharmaceutical and clinical fields. The determination of endogenous components has great potentiality as a diagnostic tool, but the use of tear as a substitute of plasma does not present clinical relevance. Levels of drugs like immunosuppressive or antibiotic agents are determined in tears to verify that pharmacological concentrations are reached and frequency of administration is deduced from kinetic fitting.
Heat Treatment Enhances Healing Process of Experimental Pseudomonas Corneal Ulcer
Authors: Nanbu Patricia Naomi , Wakabayashi Taketoshi , Yamashita Ryoko , Hayashi Hideo , Hisano Setsuji , Oshika Tetsuro
Published: August 2004

We investigated the effects of hyperthermia on the healing process of experimental Pseudomonas corneal ulceration (PCU). Hartley guinea pigs were used to develop animal models of PCU. As a heat source, disposable chemical pocket warmers were applied. The healing process of PCU was compared between the heat-treated corneas and the control corneas. The severity of infection and the degree of angiogenesis were classified by a clinical scoring system. The animals were euthanized 14 days after infection and the corneas were submitted for histopathological examination. The expression of vascular endothelial growth factor (VEGF) was examined immunohistochemically. Comparative reverse transcription polymerase chain reaction was performed to measure the expression level of VEGF in the cornea. Hyperthermia significantly promoted corneal epithelization and neovascularization in the PCU model. Heat treatment significantly decreased the number of viable Pseudomonas organisms present in PCU. On immunohistochemistry, the heated cornea demonstrated more intense staining for VEGF. Comparative reverse transcription polymerase chain reaction showed upregulation of the expression level of VEGF mRNA in the heat-treated cornea. Hyperthermia accelerated the healing process of PCU with increased corneal neovascularization. Angiogenesis may play an important role in the PCU healing process, which is enhanced by the heat treatment.
In vitro Bacterial Adherence to Ventriculoperitoneal Shunts
Authors: Livni G. , Yuhas Y. , Ashkenazi S. , Michowiz S.
Published: August 2004

Bacterial adherence to medical devices has been recognized as an important initial step in the infectious process, but it has not been fully elucidated regarding ventriculoperitoneal (VP) shunts. The aim of the present study was to quantitatively determine the adherence in vitroof bacteria known to cause VP shunt infections and to identify factors affecting the process. Clinical isolates studied included Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli. Adherence was examined quantitatively per square centimeter, visualized by electron microscopy and related to slime production and hydrophobicity. Although all four strains adhered to VP shunts, there were marked differences, with S. epidermidis and S. aureus showing the highest adherence (67.0 × 103 and 15.2 × 103 bacteria/cm2, respectively). Factors affecting adherence included incubation time and temperature, bacterial concentration, device material (lower for silicone than Teflon), slime production and hydrophobicity. These data might be helpful for devising novel strategies to reduce VP shunt infections.
Spinal Cord Compression Caused by Extradural Arachnoid Cysts
Authors: Chang I-Chang , Chou Ming-Chih , Bell William R. , Lin Zong-I.
Published: August 2004

Most spinal arachnoid cysts are asymptomatic and detected incidentally during magnetic resonance imaging or myelography. The etiology of intraspinal arachnoid cyst is not yet clear. We present two children with three spinal extradural arachnoid cysts and each cyst protruded from a separate dura defect. In both patients, plain radiographs demonstrated widening of the interpedicular distance, which suggested progressive widening of the spinal bony canal. Limited laminectomy was performed to remove the intraspinal cysts. Separate dura defects, the apparent predisposing factors, were also found and repaired. The patients completely recovered neurologically. Radical cyst removal and dura defect closure are the surgical intervention of choice in patients with symptomatic extradural arachnoid cyst.
Precedence of Cell-Zona Adhesion over Cell-Cell Adhesion during Marsupial Blastocyst Formation Prohibits Morula Formation and Ensures that both the Pluriblast and Trophoblast Are Superficial
Authors: Kress Annetrudi , Selwood Lynne
Published: August 2004

This study, based on 38 samples taken between the 16-cell stage on day 2.5 of gestation and the expanded 1.0-mm-diameter unilaminar blastocyst on day 6, describes the ultrastructural changes that occur in the conceptus of the marsupial Sminthopsis macroura in relation to cell-zonal adhesion initiated at the zygote stage and cell-cell adhesion initiated at the 16-cell stage, lineage allocation, extracellular matrix (ECM) secretion and embryo coat changes. In S. macroura, rather flattened pluriblast and rounded trophoblast cells appear as different cell types during the fourth division when nucleolar reticulation suggests activation of the zygotic genome in both cell types. The differences disappear nearly completely in blastocysts of 0.6–0.8 mm in diameter, but the two cell types then reappear as two distinct populations. The ECM varies depending on its location within the conceptus up to the stage of the expanding blastocyst. It is of rather granular appearance between the cell lining and zona pellucida and consists of patches of homogeneous material embedded in an electron-lucent substance in the cleavage cavity. Homogeneous ECM coats trophoblast but not pluriblast cells on blastocoelic surfaces. Transient structures such as ‘myosin-like’ fibrillar arrays, probably associated with exocytosis of ECM, and pearl string-like whorls are still present, but both disappear during further expansion of the 0.6- to 0.8-mm blastocyst. During blastocyst expansion, the patchy homogeneous ECM in the blastocoel changes structure and appears flocculent, while the continuous ECM coating trophoblast cells disappears. Pluriblast cells and yolk mass identify the embryonic pole and hemisphere, and the opposite hemisphere becomes abembryonic and is eventually fully lined by trophoblast cells. An increase in endocytotic, mainly coated vesicles at the apical, zona-orientated surface of both cell types is noticed and is probably responsible for uptake of the mucoid coat. In 1-mm blastocysts, numerous vesicles contain rod-shaped crystalline inclusions.
Wallerian Degeneration in the Optic Nerve of the Rabbit
Authors: Khan Aijaz Ahmed
Published: August 2004

Progressive anterograde axonal degeneration is known to follow after transection of the axon from the soma, which to some extent correlates with the passage of time after the lesion. However, the minimum time required for such changes to begin remains unresolved. In this study, 20 young adult rabbits of either sex underwent experimental monocular enucleation (left eye) under general anaesthesia. Left optic nerves from such animals were treated as experimental and those from either side of non-operated animals served as controls. Animals were sacrificed postoperatively at periods ranging from 12 h to 3 months. Brains were fixed with 10% formalin and Karnovsky fixatives by an intracardiac perfusion method. Light microscopy of 8-µm paraffin sections and 0.5-µm araldite sections from the optic nerves did not reveal any changes at 12 h. At 24 h, focal minute cavities appeared across the optic nerves. Those nerves from late postoperative stages revealed such cavities with increasing dimensions, disarray of fascicular organization, fragmentation, ovoid formation and finally dissolution of the myelin sheaths. There was an appreciable increase in the number, size and aggregation of glia cells. The debris of degeneration remained prominent even 3 months after enucleation. Electron microscopy revealed splitting of myelin, intramyelinic and periaxonal oedema and occurrence of amorphous and electron-dense materials in the degenerating nerve fibres. It was concluded that while the optic nerve showed degenerative changes as early as 24 h after enucleation, debris of degeneration was only partly removed even after 3 months.
Are the dot-like chromosomes in Trinomys iheringi (Rodentia, Echimyidae) B chromosomes?
Authors: Fagundes V. , Camacho J.P.M. , Yonenaga-Yassuda Y.
Published: August 2004

In this article we review the existing cytogenetic information on the polymorphic dot-like chromosomes in Trinomys iheringi, the only species in the family Echimyidae harboring them, and provide new data on the frequency, banding properties, meiotic behavior and DNA composition of these minute chromosomes. Since no individuals lacking these chromosomes have hitherto been found, one of the main properties of B chromosomes, i.e. dispensability, has not yet been tested, so that some reasonable doubt might exist on whether they are true B chromosomes. The dot-like chromosomes were also present in the twelve new individuals analyzed, showed intraindividual variation in number, most likely due to mitotic instability during development, failed to show C-bands, showed late-replication, paired among them in meiosis, but not with the large chromosomes, and appeared to be mainly composed of telomeric DNA. These results suggest that these dot-like chromosomes might actually be mitotically unstable micro B chromosomes showing very high frequency in the natural populations thus far analyzed. But, to be confident of this conclusion, individuals lacking the dot-like chromosomes should actively be searched in future research to test their dispensability.
Human supernumeraries: are they B chromosomes?
Authors: Fuster C. , Rigola M.A. , Egozcue J.
Published: August 2004

In humans, the presence of supernumerary chromosomes is an unusual phenomenon, which is often associated with developmental abnormalities and malformations. In contrast to most animal and plant species, the extensive knowledge of the human genome and the ample set of molecular and cytogenetic tools available have permitted to ascertain not only that most human supernumerary chromosomes (HSCs) derive from the A chromosome set, but also the specific A chromosome from which most of them arose. These extra chromosomes are classified into six types on the basis of morphology and size. There are both heterochromatic and euchromatic HSCs, the latter being more detrimental. Most are mitotically stable, except some producing individual mosaicism. No information is available on the HSC transmission rate since extensive familial studies are not usually performed generally because of death of the relatives or lack of cooperation. The main B chromosome property failing in HSCs seems to be their population spread as polymorphisms, since most HSCs seem to correspond to extra A chromosomes or centric fragments spontaneously arisen in the analysed individual or one of his/her parents. However, we cannot rule out at this moment, that more intensive studies on population distribution and frequency of those HSCs most closely resembling B chromosomes (i.e. those heterochromatic and thus less detrimental) would reveal possible HSCs polymorphisms. Although HSCs cannot be considered B chromosomes, some of them might be a source for future B chromosomes. The best candidates would be heterochromatic HSCs, which might manage to drive in either sex. To ascertain this possibility, research on inheritance and population studies would be very helpful in combination with the powerful cytogenetic and molecular tools available for our species.
Is the aneuploid chromosome in an apomictic Boechera holboellii a genuine B chromosome?
Authors: Sharbel T.F. , Voigt M.-L. , Mitchell-Olds T. , Kantama L. , de Jong H.
Published: August 2004

The Boechera holboellii complex comprises B. holboellii and B. drummondii, both of which can reproduce through sex or apomixis. Sexuality is associated with diploidy, whereas apomictic individuals can either be diploid, aneuploid or triploid. Aneuploid individuals are found in geographically and genetically distinct populations and contain a single extra chromosome. It is unknown whether the supernumerary chromosomes are shared by common descent (single origin) or have originated via introgressive hybridizations associated with the repeated transition from diploidy to triploidy. Diploid plants containing the extra chromosome(s) reproduce apomictically, suggesting that the supernumerary elements are associated with apomixis. In this study we compared flow cytometry data, chromosome morphology, and DNA sequences of sexual diploid and apomictic aneuploids in order to establish whether the extra chromosome fits the classical concept of a B chromosome. Karyotype analyses revealed that the supernumerary chromosome in the metaphase complement is heterochromatic and often smaller than the A chromosomes, and differs in length between apomictic plants from different populations. DNA sequence analyses furthermore demonstrated elevated levels of non-synonymous substitutions in one of the alleles, likely that on the aneuploid chromosome. Although the extra chromosome in apomictic Boechera does not go through normal reductional meiosis, in which it may get eliminated or accumulated by a B-chromosome-specific process, its variable size and heterochromatic nature does meet the remaining criteria for a genuine B chromosome in other species. Its prevalence and conserved genetic composition nonetheless implies that this chromosome, if truly a B, may be atypical with respect to its influence on its carriers.
The occurrence of different Bs in Cestrum intermedium and C. strigilatum (Solanaceae) evidenced by chromosome banding
Authors: Fregonezi J.N. , Rocha C. , Torezan J.M.D. , Vanzela A.L.L.
Published: August 2004

In this study, we examine the morphology, mitotic stability, meiotic behavior and the composition of heterochromatin of B chromosomes in Cestrum intermedium and C. strigilatum. The results showed that B chromosome number shows intraindividual variation in the root meristem, which seems to lead to a slight rate of B elimination in this somatic tissue. B chromosomes in both species were similar in size and shape, but differed with regard to the type, size and distribution of heterochromatin. Possible evolutionary pathways for B chromosome origin in Cestrum are discussed.
Comparative FISH analysis of distribution ofB chromosome repetitive DNA in A an d B chromosomes in two subspecies of Podisma sapporensis (Orthoptera, Acrididae)
Authors: Bugrov A.G. , Karamysheva T.V. , Rubtsov D.N. , Andreenkova O.V. , Rubtsov N.B.
Published: August 2004

FISH analysis of B chromosome repetitive DNA distribution in A and B chromosomes of two subspecies of Podisma sapporensis (P. s. sapporensis and P. s. krylonensis) was performed. In the B chromosomes, C-positive regions contained homologous DNA repeats present also in some C-positive A chromosome regions. Most C-negative regions contained DNA repeats characteristic of A chromosome euchromatic regions. The two subspecies analyzed differed in the location of A chromosome regions enriched with repeats homologous to repeats of B chromosomes. The only common region enriched with these B chromosome repeats in both subspecies was the X chromosome pericentromeric region. The origin of B chromosomes in P. sapporensis is discussed.
Different numbers of rye B chromosomes induce identical compaction changes in distinct A chromosome domains
Authors: Delgado M. , Caperta A. , Ribeiro T. , Viegas W. , Jones R.N. , Morais-Cecílio L.
Published: August 2004

In rye each B chromosome (B) represents 5.5% of the diploid A genome. Rye Bs have several nuclear to whole plant effects although they seem to bear no genes except for the ones that lead to their maintenance within a population. In this context, and considering that rye Bs are enriched in repetitive non-coding regions that build up heterochromatin (het), we investigated the influence of Bs on the organization of two chromatin fractions, namely the ribosomal DNA (facultative het) and satellite (non-het) domain of rye chromosome 1 by silver staining on root tip metaphase cells. The results show that rye Bs cause condensation both in the NOR and in the chromosome 1 satellite domain. Since the silver staining technique used is indicative of the transcriptional activity of the NORs, the condensation observed at those loci demonstrates that the rRNA gene arrays are down-regulated in the presence of Bs, regardless of their number per individual. Furthermore, the organizational changes of metaphase NORs find parallel with the interphase organization of ribosomal chromatin, since the frequency of cells with intranucleolar condensed rDNA regions increases drastically and nuclear matrix attachment pattern is altered in the presence of the Bs. Our results show an identical effect of the Bs on the organization of two distinct chromosome domains displaying a presence/absence dichotomy.