bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Analysis of Nef Functions Selected in Simian Immunodeficiency Virus-Infected Macaques
Authors: Schindler Michael , Münch Jan , Brenner Matthias , Stahl-Hennig Christiane , Skowronski Jacek , Kirchhoff Frank
Published: September 2004

A variety of simian immunodeficiency virus (SIVmac)
nef
mutants have been investigated to clarify which in vitro Nef functions contribute to efficient viral replication and pathogenicity in rhesus macaques. Most of these
nef
alleles, however, were only functionally characterized for their ability to down-modulate CD4 and class I major histocompatibility complex (MHC-I) cell surface expression and to enhance SIV replication and infectivity. To obtain information on the in vivo relevance of more recently established Nef functions, we examined the ability of a large panel of constructed SIVmac Nef mutants and of variants that emerged in infected macaques to down-regulate CD3, CD28, and MHC-II and to up-regulate the MHC-II-associated invariant chain (Ii). We found that all these four Nef functions were restored in SIV-infected macaques. In most cases, however, the initial mutations and the changes selected in vivo affected several in vitro Nef functions. For example, truncated Nef proteins that emerged in animals infected with SIVmac239 containing a 152-bp deletion in
nef
efficiently modulated both CD3 and Ii surface expression. Overall, our results suggest that the effect of Nef on each of the six cellular receptors investigated contributes to viral fitness in the infected host but also indicate that modulation of CD3, MHC-I, MHC-II, or Ii surface expression alone is insufficient for SIV virulence.
Activation of TBK1 and IKKε Kinases by Vesicular Stomatitis Virus Infection and the Role of Viral Ribonucleoprotein in the Development of Interferon Antiviral Immunity
Authors: tenOever Benjamin R. , Sharma Sonia , Zou Wen , Sun Qiang , Grandvaux Nathalie , Julkunen Ilkka , Hemmi Hiroaki , Yamamoto M. , Akira Shizuo , Yeh Wen-Chen , Lin Rongtuan , Hiscott John
Published: September 2004

Mounting an immune response to a viral pathogen involves the initial recognition of viral antigens through Toll-like receptor-dependent and -independent pathways and the subsequent triggering of signal transduction cascades. Among the many cellular kinases stimulated in response to virus infection, the noncanonical IKK-related kinases TBK1 and IKKε have been shown to phosphorylate and activate interferon regulatory factor 3 (IRF-3) and IRF-7, leading to the production of alpha/beta interferons and the development of a cellular antiviral state. In the present study, we examine the activation of TBK1 and IKKε kinases by vesicular stomatitis virus (VSV) infection in human lung epithelial A549 cells. We demonstrate that replication-competent VSV is required to induce activation of the IKK-related kinases and provide evidence that ribonucleoprotein (RNP) complex of VSV generated intracellularly during virus replication can activate TBK1 and IKKε activity. In TBK1-deficient cells, IRF-3 and IRF-7 activation is significantly reduced, although transcriptional upregulation of IKKε following treatment with VSV, double-stranded RNA, or RNP partially compensates for the loss of TBK1. Biochemical analyses with purified TBK1 and IKKε kinases in vitro demonstrate that the two kinases exhibit similar specificities with respect to IRF-3 and IRF-7 substrates and both kinases target serine residues that are important for full transcriptional activation of IRF-3 and IRF-7. These data suggest that intracellular RNP formation contributes to the early recognition of VSV infection, activates the catalytic activity of TBK1, and induces transcriptional upregulation of IKKε in epithelial cells. Induction of IKKε potentially functions as a component of the amplification mechanism involved in the establishment of the antiviral state.
Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses
Authors: Norberg Peter , Bergström Tomas , Rekabdar Elham , Lindh Magnus , Liljeqvist Jan-Åke
Published: September 2004

Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen which establishes lifelong infections. In the present study, we determined the sequence diversity of the complete genes coding for glycoproteins G (gG), I (gI), and E (gE), comprising 2.3% of the HSV-1 genome and located within the unique short (US) region, for 28 clinical HSV-1 isolates inducing oral lesions, genital lesions, or encephalitis. Laboratory strains F and KOS321 were sequenced in parallel. Phylogenetic analysis, including analysis of laboratory strain 17 (GenBank), revealed that the sequences were separated into three genetic groups. The identification of different genogroups facilitated the detection of recombinant viruses by using specific nucleotide substitutions as recombination markers. Seven of the isolates and strain 17 displayed sequences consistent with intergenic recombination, and at least four isolates were intragenic recombinants. The observed frequency of recombination based on an analysis of a short stretch of the US region suggests that most full-length HSV-1 genomes consist of a mosaic of segments from different genetic groups. Polymorphic tandem repeat regions, consisting of two to eight blocks of 21 nucleotides in the gI gene and seven to eight repeats of 3 nucleotides in the gG gene, were also detected. Laboratory strain KOS321 displayed a frameshift mutation in the gI gene with a subsequent alteration of the deduced intracellular portion of the protein. The presence of polymorphic tandem repeat regions and the different genogroup identities can be used for molecular epidemiology studies and for further detection of recombination in the HSV-1 genome.
Chorea and related disorders
Authors: Bhidayasiri R , Truong D D
Published: September 2004

Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham’s chorea is the most common form of childhood chorea, whereas Huntington’s disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.
QUANTUM-MECHANICAL DETECTION OF NON-NEWTONIAN GRAVITY
Authors: CAMACHO A.
Published: September 2004

In this work the possibility of detecting the presence of a Yukawa term, as an additional contribution to the usual Newtonian gravitational potential, is introduced. The central idea is to analyze the effects at quantum level employing interference patterns (at this respect the present proposal resembles the Colella, Overhauser and Werner experiment), and deduce from it the possible effects that this Yukawa term could have. We will prove that the corresponding interference pattern depends on the phenomenological parameters that define this kind of terms. Afterwards, using the so-called restricted path integral formalism, the case of a particle whose position is being continuously monitored, is analyzed, and the effects that this Yukawa potential could have on the measurement outputs are obtained. This allows us to obtain another scheme that could lead to the detection of these terms. This last part also renders new theoretical predictions that could enable us to confront the restricted path integral formalism against some future experiments.
A COMPLETE AND ORTHONORMAL REPRESENTATION IN TWO-MODE FOCK SPACE GAINED BY TWO-VARIABLE HERMITE POLYNOMIALS
Authors: FAN HONG-YI , ZOU HUI , FAN YUE
Published: September 2004

In terms of the two-variable Hermite polynomials' properties we derive the common eigenstates |q,λ> of two permutable operators (a†+b)(a+b†) and a†a-b†b, where q is discrete and λ is continuous. These states constitute a complete and orthonormal representation. Applications of the |q,λ> are discussed.
THE MASSLESS XXZ CHAIN WITH A BOUNDARY
Authors: KOJIMA TAKEO
Published: September 2004

We study the XXZ chain with a boundary at massless regime -1<Δ<1. We give the free field realizations of the boundary vacuum state and its dual. Using these realizations, we give the integral representations for the correlation functions.
OPEN STRING ON SYMMETRIC PRODUCT
Authors: FUJI HIROYUKI , MATSUO YUTAKA
Published: September 2004

We discuss some basic properties of the open string on the symmetric product which is supposed to describe the open string field theory in discrete light-cone quantization (DLCQ). We first derive the consistent twisted boundary conditions for Annulus/Möbius/Klein Bottle diagrams and give the explicit form of the corresponding amplitude. They have the interpretation as the long open (or closed) string amplitude but the world sheet topology viewed from the short string and from the long string is in general different. Boundary (cross-cap) states of the short string are classified into three categories, the boundary (cross-cap) states of the long string and the "joint" state which connects two strings. The partition function has the typical structure of the string field theory in DLCQ. Tadpole condition is also analyzed and gives a reasonable gauge group SO(213).
PHOTON–AXION CONVERSION CROSS-SECTIONS IN AN ELECTROMAGNETIC FIELD
Authors: SOA DANG VAN , BANG HA HUY
Published: September 2004

Photon–axion conversions in static magnetic fields and in a periodic field with frequency equal to the axion mass are considered in detail by the Feynman diagram methods. The differential cross-sections are presented and numerical evaluations are given. It is shown that there is a resonant conversion for the considered process. Some estimates for experimental conditions are given from our results.
THE IMPORTANCE OF CONSERVATIVE SELF FORCES FOR BINARIES UNDERGOING RADIATION DAMPING
Authors: BURKO LIOR M.
Published: September 2004

We consider the radial, conservative self force for simple systems undergoing gravitational-radiation damping in the extreme mass ratio limit. We argue that the conservative force acting on a pointlike mass in orbit around a black hole may have a measurable effect on the wave forms, via an induced (retrograde) cumulative precession of the periastron. This effect is strongest for high values of the orbital eccentricity. We also show that the nonradiative modes of the field contribute to the total conservative force.
STRINGS IN AdS3 AND THE SL(2, R) WZW MODEL
Authors: OOGURI HIROSI
Published: September 2004

Strings in the three-dimensional anti-de Sitter space in the NS background is described by the SL(2, R) WZW model. We present a complete description of the Hilbert space of the model. We then compute the one-loop partition function for Euclidean BTZ black hole backgrounds or equivalently thermal AdS3 backgrounds which are quotients of Euclidean AdS3. We see long strings and discrete states in agreement with the structure of the Hilbert space.
OVERVIEW OF K-THEORY APPLIED TO STRINGS
Authors: WITTEN EDWARD
Published: September 2004

K-theory provides a framework for classifying Ramond-Ramond (RR) charges and fields. K-theory of manifolds has a natural extension to K-theory of noncommutative algebras, such as the algebras considered in noncommutative Yang-Mills theory or in open string field theory. In a number of concrete problems, the K-theory analysis proceeds most naturally if one starts out with an infinite set of D-branes, reduced by tachyon condensation to a finite set. This suggests that string field theory should be reconsidered for N=∞.
ASYMPTOTICALLY ANTI-DE SITTER SPACETIMES AND THEIR STRESS ENERGY TENSOR
Authors: SKENDERIS KOSTAS
Published: September 2004

We consider asymptotically anti-de Sitter spacetimes in general dimensions. We review the origin of infrared divergences in the on-shell gravitational action, and the construction of the renormalized on-shell action by the addition of boundary counterterms. In odd dimensions, the renormalized on-shell action is not invariant under bulk diffeomorphisms that yield conformal transformations in the boundary (holographic Weyl anomaly). We obtain formulae for the gravitational stress energy tensor, defined as the metric variation of the renormalized on-shell action, in terms of coefficients in the asymptotic expansion of the metric near infinity. The stress energy tensor transforms anomalously under bulk diffeomorphisms broken by infrared divergences.
LOCALLY LOCALIZED GRAVITY
Authors: KARCH ANDREAS , RANDALL LISA
Published: September 2004

We study the fluctuation spectrum of linearized gravity around non-fine-tuned branes. We focus on the case of an AdS 4 brane in AdS 5. In this case, for small cosmological constant, the warp factor near the brane is essentially that of a Minkowski brane. However, far from the brane, the metric differs substantially. The space includes the AdS 5 boundary, so it has infinite volume. Nonetheless, for sufficiently small AdS 4 cosmological constant, there is a bound state graviton in the theory, and four-dimensional gravity is reproduced. However, it is a massive bound state that plays the role of the four-dimensional graviton.
1+1 DIMENSIONAL NCOS AND ITS U(N) GAUGE THEORY DUAL
Authors: KLEBANOV IGOR R. , MALDACENA JUAN
Published: September 2004

We study some aspects of open string theories on D-branes with critical electric fields. We show that the massless open string modes that move in the direction of the electric field decouple. In the 1+1 dimensional case the dual theory is U(N) SYM with electric flux, and the decoupling of massless open strings is dual to the decoupling of the U(1) degrees of freedom. We also show that, if the direction along the electric field is compact, then there are finite energy winding closed string modes. They are dual to Higgs branch excitations of the SYM theory, and their energetics works accordingly. These properties provide new non-trivial evidence for the duality.
Na+/H+ exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes
Authors: Baumgartner Martin , Patel Hitesh , Barber Diane L.
Published: September 2004

The plasma membrane Na+/H+ exchanger NHE1 has an established function in intracellular pH and cell volume homeostasis by catalyzing electroneutral influx of extracellular Na+ and efflux of intracellular H+. A second function of NHE1 as a structural anchor for actin filaments through its direct binding of the ezrin, radixin, and moesin (ERM) family of actin-binding proteins was recently identified. ERM protein binding and actin anchoring by NHE1 are necessary to retain the localization of NHE1 in specialized plasma membrane domains and to promote cytoskeleton-dependent processes, including actin filament bundling and cell-substrate adhesions. This review explores a third function of NHE1, as a plasma membrane scaffold in the assembly of signaling complexes. Through its coordinate functions in H+ efflux, actin anchoring, and scaffolding, we propose that NHE1 promotes protein interactions and activities, assembles signaling complexes in specialized plasma membrane domains, and coordinates divergent signaling pathways.
Expression of epidermal growth factor in the developing rat kidney
Authors: Jung Ju-Young , Song Ji-Hyun , Li Can , Yang Chul-Woo , Kang Tae-Cheon , Won Moo-Ho , Jeong Young-Gil , Han Ki-Hwan , Choi Kyu-Bok , Lee Seung-Hun , Kim Jin
Published: September 2004

Epidermal growth factor (EGF) is important in mammalian renal development. In our study, we investigated the detailed distribution and the time of the first appearance of EGF in developing rat kidney. Kidneys from embryonic 18 ( E18)- and 20-day-old ( E20) fetuses, postnatal 1 ( P1)-, 3 ( P3)-, 7 ( P7)-, 14 ( P14)-, and 21-day-old ( P21) pups, and adults were processed for immunohistochemistry and electronmicroscopy. In adult rat kidney, EGF immunoreactivity was found in distal tubule including the thick ascending limb (TAL) and portion 1 of distal convoluted tubule (DCT1), whereas no EGF immunoreactivity was seen in portion 2 of distal convoluted tubule (DCT2) and connecting tubule. In developing kidney, EGF-positive cells first appeared at P3 and were localized in the middle portion of the differentiating TAL of the corticomedullary junction. By P7, the abundance of EGF expression had dramatically increased in the medullary TAL. Between P14 and P21, EGF immunoreactivity was found in the TAL and the DCT for the first time. However, EGF-positive and EGF-negative cells were in the TAL in developing rat kidney. EGF-positive cells did not differ from negative cells in the expression of sodium transport proteins or in the proliferation rate at P3 and P7. In the TAL, smooth-surfaced cells had strong EGF immunoreactivity, but no EGF immunoreactivity was seen in the rough-surfaced cells with well-developed microvilli. Our results suggest that the expression of EGF in developing kidney plays an important role in the regulation of growth and differentiation of the loop of Henle during kidney development and that this may act in the paracrine mode.
Angiotensin II Excites Paraventricular Nucleus Neurons That Innervate the Rostral Ventrolateral Medulla: An In Vitro Patch-Clamp Study in Brain Slices
Authors: Cato Matthew J. , Toney Glenn M.
Published: September 2004

Neurons of the hypothalamic paraventricular nucleus (PVN) are key controllers of sympathetic nerve activity and receive input from angiotensin II (ANG II)–containing neurons in the forebrain. This study determined the effect of ANG II on PVN neurons that innervate in the rostral ventrolateral medulla (RVLM)—a brain stem site critical for maintaining sympathetic outflow and arterial pressure. Using an in vitro brain slice preparation, whole cell patch-clamp recordings were made from PVN neurons retrogradely labeled from the ipsilateral RVLM of rats. Of 71 neurons tested, 62 (87%) responded to ANG II. In current-clamp mode, bath-applied ANG II (2 μM) significantly ( P < 0.05) depolarized membrane potential from −58.5 ± 2.5 to −54.5 ± 2.0 mV and increased the frequency of action potential discharge from 0.7 ± 0.3 to 2.8 ± 0.8 Hz ( n = 4). Local application of ANG II by low-pressure ejection from a glass pipette (2 pmol, 0.4 nl, 5 s) also elicited rapid and reproducible excitation in 17 of 20 cells. In this group, membrane potential depolarization averaged 21.5 ± 4.1 mV, and spike activity increased from 0.7 ± 0.4 to 21.3 ± 3.3 Hz. In voltage-clamp mode, 41 of 47 neurons responded to pressure-ejected ANG II with a dose-dependent inward current that averaged -54.7 ± 3.9 pA at a maximally effective dose of 2.0 pmol. Blockade of ANG II AT1 receptors significantly reduced discharge ( P < 0.001, n = 5), depolarization ( P < 0.05, n = 3), and inward current ( P < 0.01, n = 11) responses to locally applied ANG II. In six of six cells tested, membrane input conductance increased ( P < 0.001) during local application of ANG II (2 pmol), suggesting influx of cations. The ANG II current reversed polarity at +2.2 ± 2.2 mV ( n = 9) and was blocked ( P < 0.01) by bath perfusion with gadolinium (Gd3+, 100 μM, n = 8), suggesting that ANG II activates membrane channels that are nonselectively permeable to cations. These findings indicate that ANG II excites PVN neurons that innervate the ipsilateral RVLM by a mechanism that depends on activation of AT1 receptors and gating of one or more classes of ion channels that result in a mixed cation current.
The Molecular Synaptosomal Deficit in Down Syndrome Starts Early in Life
Authors: Pollak Daniela , Fountoulakis Michael , Lubec Gert
Published: September 2004

Information about brain abnormalities in early prenatal life leading to or representing mental retardation in Down syndrome (DS) is limited. Synaptic dysgenesis was described and is considered the morphological correlate of mental retardation. The availability of appropriate fetal brain samples along with the advent of proteomic technologies unambiguously identifying proteins concomitantly made us study synaptosomal structures at the molecular level in the fetal cortex of controls and DS fetuses. Cortical tissue of seven controls (mean 18.8 weeks of gestation) and eight DS fetuses (mean 19.8 weeks of gestation) was homogenized, proteins were extracted and run on two-dimensional gel electrophoresis followed by mass spectrometrical analysis using MALDI-TOF (matrix-assisted laser desorption ionization – time of flight). Levels of synaptic proteins N-ethylmaleimide-sensitive fusion protein (controls: mean 0.030 ± 0.015; DS: mean 0.011 ± 0.008 O.D.), synaptotagmin I (controls: mean 0.038 ± 0.021; DS: mean 0.010 ± 0.002 O.D.) and septin 3 (controls: mean 0.061 ± 0.002; DS: mean 0.019 ± 0.012 O.D.) were significantly decreased in brains of fetuses with DS. It is concluded that an altered expression of synaptosomal proteins at the time of the early second trimester of gestation may form the structural basis for the brain deficit in DS early in life.
Migration of Hindbrain Neural Crest Cells in the Mouse
Authors: Cheung Chui Shan , Wang Liang , Dong Ming , Chan Wood Yee
Published: September 2004

Background: Neural crest cells are a special group of embryonic cells which are able to emigrate from the dorsal neural tube (the developing central nervous system) to the mesenchyme and form different derivatives in embryos. In contrast to the situation in the avian embryo, where the use of quail-chick chimeras has provided much information on neural crest migration, the early migratory pathways of hindbrain neural crest cells are not well understood in mammals. Aims: In the present study, an exogenous dye, wheat germ agglutinin-gold conjugate (WGA-Au), was used to label the early migrating hindbrain neural crest cells to track their migration at three axial levels, namely (1) pre-otic, (2) post-otic and pre-somitic, and (3) somitic (somites 1–4) levels, in mouse embryos cultured in vitro. Results: It was found that neural crest cells had already started their emigration from the dorsal part of the neural tube at the 9-somite stage and migrated into the mesenchyme subjacent to the neural tube. When the labelled embryos were cultured to more advanced stages, neural crest cells migrated to more ventral regions. At the 13-somite stage, most neural crest cells at the pre-somitic hindbrain migrated to the mesenchyme lateral to the dorsal aorta, while by the 17-somite stage, labelled cells reached the mesenchyme adjacent to the pharynx, which is located more ventrally than the dorsal aorta. At the 21-somite stage, more labelled cells were found in the mesenchyme lateral and ventral to the pharynx. At the somitic level, neural crest cells migrated along three distinct routes, namely the dorsolateral (between the surface epithelium and the somite), medial (between the somite and the neural tube) and intersomitic (between two consecutive somites) pathways. Conclusions: Our results indicate that whole embryo culture is able to support the normal development of mouse embryos at early organogenesis in vitro for 26 h, and that WGA-Au is an ideal short-term cell marker for tracking neural crest migration in the mouse. We also show that the migratory patterns of hindbrain neural crest cells in the mouse largely resemble those observed in the chick.
Is the Treatment of Hodgkin’s Disease Detrimental to the Parathyroid Gland?
Authors: Miltényi Zsófia , Keresztes Katalin , Lakos Gabriella , Váróczy László , Miltényi László , Illés Árpád
Published: September 2004

The thyroid gland is often injured by supradiaphragmatic irradiation for Hodgkin’s lymphoma. The aim of the present study was to examine whether the parathyroid gland gets injured by the treatment for Hodgkin’s disease. Calcium, phosphorus and parathormone levels of 143 patients with primary treatment for Hodgkin’s disease and in complete remission for 2 years were measured as well as the presence of antiparathyroid antibody in patients having antithyroid antibody. Out of the 143 patients studied, 104 received neck irradiation (with or without chemotherapy); among them laboratory alterations were observed in 7 cases. 39 patients received only chemotherapy; 3 of them had alterations. In contrast to the injury of the thyroid gland, no damage to the parathyroid glands associated with the treatment for Hodgkin’s disease was noted. It has been concluded that the use of high-dose external radiotherapy does not mean a higher risk as regards the parathyroid gland but further follow-up studies of the patients may result in the revelation of the development of parathyroid lesions.
Eyes: Variety, Development and Evolution
Authors: Fernald Russell D.
Published: September 2004

The selective advantages of using light as a source of information are reflected in the diverse types of extant eyes. The physical properties of light restrict how it can be collected and processed, resulting in only eight known optical systems found in animals. Eyes develop through tissue rearrangement and differentiation. Our understanding of the source of genetic information used in developmental programs is growing rapidly and reveals distributions of gene expression with substantial overlap in both time and space. Specific genes and their products are used repeatedly, making causal relationships more difficult to discern. The phenomenon of groups of genes acting together seems to be the rule. Throughout evolution, particular genes have become associated with distinct aspects of eye development, and these suites of genes have been recruited repeatedly as new eyes evolved.
Lateral Line Receptors: Where Do They Come from Developmentally and Where Is Our Research Going?
Authors: Gibbs Melissa Ann
Published: September 2004

The lateral line system is composed of both mechanoreceptors, which exhibit little variation in structure between taxonomic groups, and electroreceptors, which exhibit considerably more variation. Cathodally sensitive ampullary electroreceptors are the primitive condition and are found in agnathans, chondrichthyans, and most osteichthyans. Aquatic amphibians also have ampullary electroreceptors for at least part of their life cycle. The more recently evolved anodally sensitive ampullary electroreceptors and tuberous electroreceptors are only found in four groups of teleost fishes. The basic ontogenetic unit of lateral line development is the dorsolateral placode. Primitively, there are six pairs of placodes, which pass through sequential stages of development into lateral line receptors. There is no question about the origin of primitive mechanoreceptors or electroreceptors, however, we do not have a good understanding of the origin of teleost mechanoreceptors and their ampullary or tuberous electroreceptors; do they come exclusively from dorsolateral placodes or from neural crest or even general ectoderm? A second intriguing lateral line question is how certain teleost fish groups evolved tuberous electroreceptors. Electroreception appears to have re-evolved at least twice in teleosts after being lost during the neopterygian radiation. It has been suggested that the development of tuberous electroreceptors might be due to changes in placodal patterning or a change in the general ectoderm that placodes arise from. Unfortunately, our understanding of lateral line origins in fishes is very sketchy, and, if we are to answer such an evolutionary question, we first need more complete information about lateral line development in a variety of fishes, which can then be combined with gene expression data to better interpret lateral line receptor development.
Taste Buds: Development and Evolution
Authors: Northcutt R. Glenn
Published: September 2004

The gustatory system in vertebrates comprises peripheral receptors (taste buds), innervated by three cranial nerves (VII, IX, and X), and a series of central neural centers and pathways. All vertebrates, with the exception of hagfishes, have taste buds. These receptors vary morphologically in different vertebrates but usually consist of at least four types of cells (dark, light, basal, and stem cells). An out-group analysis indicates that taste buds were restricted to the oropharynx, primitively, and that external taste buds, distributed over the head and, in some cases, even the trunk, evolved a number of times independently. The sensory neurons of the cranial nerves that innervate taste buds are believed to arise from epibranchial placodes, which are induced by pharyngeal endoderm, but it has never been demonstrated experimentally that these sensory neurons do, in fact, arise from these placodes. Although many details of the development of the innervation of taste buds are still unknown, it is now clear that taste buds are induced from either ecto- or endodermal epithelia, rather than arising from either placodes or neural crest. At present, there are two developmental models of taste bud induction: The neural induction model claims that peripheral nerve fibers induce taste buds, whereas the early specification model claims that oropharyngeal epithelium is specified by or during gastrulation and that taste buds arise from cell-cell interactions within the specified epithelium. There is now substantial evidence that the early specification model best describes the induction of taste buds.
Pattern of Renal Function Recovery after Leptospirosis Acute Renal Failure
Authors: De Francesco Daher Elizabeth , Zanetta Dirce Maria T. , Abdulkader Regina C.R.M.
Published: September 2004

Background: Although acute renal failure (ARF) is a frequent complication of severe leptospirosis, there are few studies on renal function recovery in the literature. The objective of the present study was to verify how and when renal function recovery occurs after leptospirosis ARF. Patients and Methods: 35 patients with leptospirosis ARF (plasma creatinine [Pcreat] ≧133 µmol/l at hospital admission) were prospectively studied during hospitalization, at discharge and 3 and 6 months after discharge. Creatinine clearance, fractional excretion of sodium and potassium, proteinuria and sodium proximal reabsorption were measured under normal sodium diet. Urinary pH and the ratio urinary to plasma osmolality (U/Posm) were measured 18 h after food and water withdrawal. All parameters were also measured in 18 healthy volunteers. Presence of laboratorial alterations usually found in leptospirosis were evaluated in the patients. Patients were divided in 2 groups according to their maximum Pcreat value during hospitalization: group 1 ( Pcreat >442 µmol/l, n = 21), and group 2 (Pcreat ≤442 µmol/l, n = 14). Results: All patients presented with jaundice, fever and myalgia. Bilirubin and creatine kinase were higher in group 1. Oliguria was observed in 11% of all patients and 49% required dialysis; all these patients were from group 1. All renal parameters were normal at the 6th month except U/Posm that remained lower than normal. The pattern of renal function recovery was similar in both groups except for urinary volume. Conclusion: After leptospirosis ARF, renal function recovery is fast and complete after 6 months, except for urinary concentration capacity.
A Simple, Safe and Effective Citrate Anticoagulation Protocol for the Genius® Dialysis System in Acute Renal Failure
Authors: Morgera Stanislao , Scholle Cornelia , Melzer Christoph , Slowinski Torsten , Liefeld Lutz , Baumann Gerd , Peters Harm , Neumayer Hans-H.
Published: September 2004

Background: The Genius® dialysis system is a close loop dialysis batch system increasingly used as an intermittent hemodialysis device in intensive care units. The aim of this study was to test the safety and feasibility of a regional citrate anticoagulation protocol with respect to acid-base and electrolyte disarrangements in critically ill patients with acute renal failure. A standard heparin anticoagulation protocol served as control. Methods and Results: In a cross-over study design, 27 acute renal failure patients were allocated to a citrate- and heparin-anticoagulated dialysis sessions (4–6 h). For citrate anticoagulation, a 4% sodium-citrate solution was infused into the arterial line of the extracorporeal circuit. A low calcium dialysate (1 mmol/l) was used for all dialysis sessions. Citrate dosing was adjusted according to the post-filter ionized calcium concentration (targeted values 0.5–0.7 mmol/l). There was no routine calcium substitution. Heparin anticoagulation was started with a heparin-loading dose followed by an individual, patient-adjusted continuous heparin infusion. Electrolyte disarrangements, namely hypernatremia, hypo- and hypercalcemia did not occur in either group. Although the highest bicarbonate levels were achieved during citrate anticoagulation (p = 0.021 versus heparin) the acid base values remained equilibrated in both groups. Filter longevity was excellent and the targeted dialysis time was achieved in all but 1 patient. Citrate anticoagulation was well tolerated with respect to cardiovascular hemodynamics. Conclusions: Citrate anticoagulation can be safely and effectively performed during intermittent Genius® dialysis. Calcium supplementation is not routinely required.
Elevated Levels of IgG and IgG4 to Malassezia Allergens in Atopic Eczema Patients with IgE Reactivity to Malassezia
Authors: Johansson Catharina , Tengvall Linder Maria , Aalberse Rob C. , Scheynius Annika
Published: September 2004

Background: The opportunistic yeast Malassezia is considered to be one of the factors that can contribute to atopic eczema (AE). Elevated serum IgE levels, T-cell proliferation and positive skin prick test (SPT) and atopy patch test (APT) reactions to Malassezia are found among AE patients. Methods: Sera from 127 AE patients, 14 patients with seborrheic dermatitis (SD) and 33 healthy controls were investigated for IgE and IgG4 to M. sympodialis extract and four recombinant Malassezia allergens; rMala s 1, rMala s 5, rMala s 6, and rMala s 9. In addition, IgG to the recombinant allergens was analyzed. The IgG and IgG4 levels were compared to IgE levels and in vivo reactions (SPT and APT) to Malassezia. Results: AE patients with serum IgE levels >0.35 kU/l to M. sympodialis extract had significantly higher IgG4 levels to M. sympodialis extract than AE patients without detectable serum IgE to M. sympodialis extract, SD patients and healthy controls. Among the AE patients with and without detectable serum IgE to M. sympodialis extract, respectively, there were no differences in IgG4 levels between patients with positive or negative in vivo reactions to M. sympodialis extract. IgG4 to the rMala s allergens was almost exclusively found among patients with IgE to the same allergen. Within the four tested rMala s allergens, most IgG4 reactions were found to rMala s 6, an allergen with homology to cyclophilin. Conclusions: Elevated serum IgG4 to M. sympodialis extract accompanies elevated serum IgE to the extract. This is further confirmed by the association between IgG/IgG4 and IgE to recombinant Malassezia allergens.
Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans
Authors: Kaufmann Philipp A. , Rimoldi Ornella , Gnecchi-Ruscone Tomaso , Bonser Robert S. , Lüscher Thomas F. , Camici Paolo G.
Published: September 2004

Background—

Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients.

Methods and Results—

MBF (mL · min
−1
· g
−1
) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and
15
O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg
N
G
-monomethyl-
l
-arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n=13), 10 mg/kg L-NMMA; group 4 (n=8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%,
P
<0.0001 versus baseline) and CFR (+52%,
P
<0.0001 versus baseline) increased in group 3, whereas they remained unchanged in group 5, which suggests that an intact cardiac innervation was required for the increase in MBF and CFR observed in group 3.

Conclusions—

The results of the present study suggest that maximal adenosine-induced hyperemia and CFR in humans are constrained by neurally mediated vasoconstriction, which can be relieved by systemic NOS inhibition with L-NMMA.
Plasma Level of B-Type Natriuretic Peptide as a Prognostic Marker After Acute Myocardial Infarction
Authors: Suzuki Satoru , Yoshimura Michihiro , Nakayama Masafumi , Mizuno Yuji , Harada Eisaku , Ito Teruhiko , Nakamura Shota , Abe Koji , Yamamuro Megumi , Sakamoto Tomohiro , Saito Yoshihiko , Nakao Kazuwa , Yasue Hirofumi , Ogawa Hisao
Published: September 2004

Background—

Circulating levels of B-type natriuretic peptide (BNP), a cardiac hormone, reflect the severity of cardiac dysfunction. Because the plasma BNP level changes dramatically during the period after the onset of acute myocardial infarction (AMI), identification of a suitable sampling time is problematic. There have been several reports indicating that the plasma BNP level obtained in the acute phase of AMI can be used as a prognostic marker. We examined whether the plasma BNP level measured 3 to 4 weeks after the onset of AMI represents a reliable prognostic marker for patients with AMI.

Methods and Results—

We analyzed 145 consecutive patients with AMI. Plasma BNP levels were measured during the 3 to 4 weeks after onset of AMI. Of those patients, 23 experienced fatal cardiac events during this study. The mean follow-up period was 58.6 months. Log BNP, left ventricular end-diastolic pressure, and pulmonary vascular resistance were all significantly higher in the cardiac death group, and there were more men and more patients with a history of heart failure in the cardiac death group. A Cox proportional hazards model analysis showed that log BNP was an independent predictor of cardiac death. The survival rate was significantly higher in patients with log BNP <2.26 (180 pg/mL) than in those with log BNP ≥2.26.

Conclusions—

The plasma BNP level obtained 3 to 4 weeks after the onset of AMI can be used as an independent predictor of cardiac death in patients with AMI.
Mechanisms of Organized Left Atrial Tachycardias Occurring After Pulmonary Vein Isolation
Authors: Gerstenfeld Edward P. , Callans David J. , Dixit Sanjay , Russo Andrea M. , Nayak Hemal , Lin David , Pulliam Ward , Siddique Sultan , Marchlinski Francis E.
Published: September 2004

Background—

A proarrhythmic consequence of pulmonary vein (PV) isolation can be a recurrent organized left atrial (LA) tachycardia after ablation. This arrhythmia is frequently referred to as “left atrial flutter,” but the mechanism and best ablation strategy have not been determined.

Methods and Results—

Isolation of arrhythmogenic PVs was initially performed by segmental ostial PV ablation guided by a circular mapping catheter in 341 patients. Patients whose predominant recurrent arrhythmia was a persistent organized tachycardia returned for mapping and ablation. Recurrent organized LA tachycardias (cycle length 253±33 ms, range 213 to 328 ms) occurred in 10 (2.9%) of 341 patients (age 59±9 years, 1 woman). Mapping was consistent with a focal origin in 8 patients and with macroreentry in 1 patient and was unclear in 1 patient owing to degeneration to atrial fibrillation. Focal tachycardias originated from reconnected segments of prior isolated PVs (6 patients), the posterior LA (1 patient), or the superior septum (1 patient). Focal atrial tachycardias were ablated with point lesions that targeted the earliest activation. All reconnected PVs were also reisolated. Reentrant LA flutter occurred around the left PVs in 1 patient. After 6.7±2.3 months of follow-up, 9 (90%) of 10 patients were arrhythmia free (4 of whom were taking antiarrhythmic drug therapy), and one was having recurrent atrial fibrillation.

Conclusions—

Recurrent organized LA tachycardia after PV isolation is uncommon and typically has a focal origin from reconnected PV ostia. Reisolation of the PV and ablation of non-PV foci are sufficient to treat this proarrhythmia. Linear lesions are only required when a macroreentrant mechanism is present.
Effectiveness of β-Blockade in Experimental Chronic Aortic Regurgitation
Authors: Plante Eric , Lachance Dominic , Gaudreau Martin , Drolet Marie-Claude , Roussel Élise , Arsenault Marie , Couet Jacques
Published: September 2004

Background—

Past studies have suggested that the adrenergic system becomes abnormally activated in chronic volume overload, such as in severe aortic valve regurgitation (AR). However, the effectiveness of agents directed against this adrenergic activation has never been adequately tested in chronic AR. We therefore tested the effects of metoprolol treatment on the left ventricular (LV) function and remodeling in severe chronic AR in rats.

Methods and Results—

Severe AR was created in adult male Wistar rats by retrograde puncture of the aortic leaflets under echocardiographic guidance. Two weeks later, some animals received metoprolol treatment (25 mg/kg) orally for 24 weeks, and some were left untreated. LV dimensions, ejection fraction, and filling parameters were evaluated by echocardiography. Hearts were harvested at 1, 2, 14, and 180 days for the evaluation of hypertrophy, β-adrenergic receptor status, and extracellular matrix remodeling. We found that metoprolol treatment prevented LV dilatation and preserved the ejection fraction and filling parameters compared with untreated animals. Metoprolol increased the expression of β
1
-adrenoreceptor mRNA and reduced G protein receptor kinase 2 levels. Collagen I and III mRNA levels were reduced. Cardiac myocyte hypertrophy was also prevented.

Conclusions—

In our experimental model of severe AR, metoprolol treatment had a significant beneficial global effect on LV remodeling and function. These results suggest that the adrenergic system is important in the development of volume-overload cardiomyopathy in AR and that adrenergic-blocking agents may play a role in the treatment of this disease.
Determination of Human Ventricular Repolarization by Noncontact Mapping
Authors: Yue Arthur M. , Paisey John R. , Robinson Steve , Betts Tim R. , Roberts Paul R. , Morgan John M.
Published: September 2004

Background—

Noncontact mapping (NCM) has not been validated as a clinical technique to measure ventricular repolarization. We used NCM to determine repolarization characteristics by analysis of reconstructed unipolar electrograms (UEs) at the same sites as monophasic action potential (MAP) recordings in the human ventricle.

Methods and Results—

MAPs were recorded from a total of 355 beats at 46 sites in the left or right ventricle of 9 patients undergoing ablation of ventricular tachycardia guided by NCM (EnSite system). Measurements were made during sinus rhythm, constant right ventricular pacing, and ventricular extrastimuli during restitution-curve construction. The EnGuide locator signal was used to document MAP catheter locations on the endocardial geometry. UE-determined activation-recovery interval (ARI) measured at the maximum derivative of the T wave (Wyatt method) and the minimum derivative of the positive T wave (alternative method) was correlated with MAP measured at 90% repolarization (MAP90%) at the same sites. ARI correlated with MAP90% during steady state by the Wyatt method (
r
=0.83,
P
<0.001) and the alternative method (
r
=0.94,
P
<0.001). Restitution curves constructed from MAP and UE data exhibited the same characteristics, with a mean correlation coefficient of 0.95 (range, 0.90 to 0.99,
P
<0.001). The error between ARI and MAP90% was greater over a shorter diastolic coupling interval but was not influenced by distance of the sampling site from the multielectrode array.

Conclusions—

NCM accurately determines steady-state and dynamic endocardial repolarization in humans. Global, high-density, NCM data could be used to characterize abnormalities of human ventricular repolarization.
Major Vascular Anomalies in Turner Syndrome
Authors: Ho Vincent B. , Bakalov Vladimir K. , Cooley Margaret , Van Phillip L. , Hood Maureen N. , Burklow Thomas R. , Bondy Carolyn A.
Published: September 2004

Background—

Turner syndrome (TS) is associated with aortic coarctation and dissection; hence, echocardiographic evaluation of all patients is currently recommended. X-ray angiography in clinically symptomatic patients has suggested a range of other vascular anomalies, but the true prevalence of such lesions in TS is unknown. To better understand the prevalence and pathogenesis of cardiovascular defects in TS, we prospectively evaluated a group of asymptomatic adult volunteers with TS using magnetic resonance (MR) angiography.

Methods and Results—

A total of 85 adults with TS and 27 normal female adult volunteers underwent gadolinium-enhanced 3D MR angiography. A high prevalence of aortic anomalies was seen in women with TS, including elongation of the transverse arch (49%), aortic coarctation (12%), and aberrant right subclavian artery (8%). Venous anomalies were also prominent, including persistent left superior vena cava (13%) and partial anomalous pulmonary venous return (13%). None of these anomalies were found in healthy female controls. The constellation of elongation of the transverse arch, aortic coarctation, and persistent left superior vena cava was significantly associated with women with TS. Neck webbing and increased thoracic anterior-to-posterior dimension diameters were strong predictors for arterial and venous anomalies.

Conclusions—

Thoracic vascular anomalies are common in TS, occurring in ≈50% of a group not preselected for cardiovascular disease. The highly significant association between neck webbing, increased chest diameter, and these vascular anomalies suggests that in utero, centrally localized lymphatic obstruction may contribute to these cardiovascular deformities in TS. Improved recognition of these often-undetected vascular lesions may be important for identification of patients in need of closer cardiovascular monitoring.