bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient emission suppression tuning curve attributes in relation to psychoacoustic threshold
Authors: Zettner Erika M. , Folsom Richard C.
Published: March 2003

Ipsilateral suppression characteristics of transiently evoked otoacoustic emissions (TEOAEs) are described in relation to psychoacoustic threshold at 4000 Hz and the presence or absence of spontaneous otoacoustic emissions in 41 adults with normal hearing. TEOAE amplitudes were measured in response to 4000-Hz tonebursts presented in linear blocks at 40 and 50 dB SPL while puretone suppressors were introduced at a variety of frequencies and levels ipsilateral to and simultaneously with the tonebursts. Suppressors close to the toneburst frequency were most effective in decreasing the amplitude of the TEOAEs, while those more remote in frequency required significantly greater intensity for a similar amount of suppression. Consequently, characteristic tuning curve shapes were obtained. Tuning-curve tip levels were closely associated with the level of the toneburst and tip frequencies occurred at or above the toneburst frequency. Tuning-curve widths (Q10), however, varied significantly across subjects with similar psychoacoustic thresholds in quiet determined by a two-alternative forced-choice method. The results suggest that a portion of that variability may be explained by the presence or absence of spontaneous otoacoustic emissions in an individual ear.
MR-CISD and MR-AQCC Calculation of Excited States of Malonaldehyde: Geometry Optimizations Using Analytical Energy Gradient Methods and a Systematic Investigation of Reference Configuration Sets
Authors: Monte Silmar A. do , Dallos Michal , Müller Thomas , Lischka Hans
Published: March 2003

Extended MR-CISD and MR-AQCC calculations have been performed on the ground state and the first two excited states of malonaldehyde. Full geometry optimizations have been carried for Cs and C2v structures both at MR-CISD and MR-AQCC levels. Vertical and minimum-to-minimum excitation energies and oscillator strengths have been computed. Systematic studies have been undertaken concerning several types of reference spaces. Agreement with the experimental 0-0 transition energy to the S1 state (expt. 3.50 eV, calc. 3.56 eV) and for the vertical excitation to S2 (expt. band maximum 4.71 eV, best estimate 4.86 eV) is very good. In agreement with the CASSCF/CASPT2 results by Sobolewski and Domcke (J. Phys. Chem. A 1999, 103, 4494), we find that the hydrogen bond in malonaldehyde is weakened by excitation to the S1 state. The barrier for proton transfer in the S1 state is increased in comparison with the ground state.
Modeling of the Three-Body Effects in the Neutral Trimers in the Quartet State by ab initio Calculations. H3, Na3, and Na2B
Authors: Jakowski Jacek , Chałasiński Grzegorz , Szczęśniak Małgorzata M. , Cybulski Slawomir M.
Published: March 2003

The Na2B, Na3, and H3 trimers in the lowest quartet states were studied by ab initio methods, using both the supermolecular approach and the intermolecular Møller-Plesset perturbation theory. Partitioning of the nonadditive contribution into the orientational two-body part and the genuine three-body part was proposed. The lowest quartet state of the Na3 trimer and all the three lowest quartet states of the Na2B trimer are bound, and the forms of these clusters are essentially determined by two-body forces. In the case of the Na2B trimer the orientational two-body nonadditivity proved to be crucial. In addition, in the title metal trimers, in the region of the van der Waals minima, the genuine nonadditivity is very important, and amounts to 30% in Na2B and up to 70% in Na3. The leading nonadditive term is the triple-exchange Heitler-London exchange term. For triangular arrangements it considerably enhances the total stabilization. The single-exchange term and the SCF deformation play only a secondary role. The dispersion nonadditivity is negligible. The isotropic part of the basis set superposition error (BSSE) is large and must be corrected by the counterpoise method. The anisotropic contribution to BSSE is practically negligible.
A Proposed Mechanism of [closo-CB11H12]- Formation by Dichlorocarbene Insertion Into [nido-B11H14]-. A Computational Study by Density Functional Theory
Authors: Rempala Pawel , Michl Josef
Published: March 2003

A plausible mechanism is proposed for the insertion of dichlorocarbene into [nido-B11H14]- to yield [closo-CB11H12]- and is supported by the results of density functional theory and ab initio calculations.
SEMICLASSICAL QUANTIZATION OF SUPERSTRINGS: AdS5 × S5 AND BEYOND
Authors: TSEYTLIN A. A.
Published: March 2003

We discuss semiclassical quantization of closed superstrings in AdS 5 × S 5. We consider two basic examples: point-like string boosted along a large circle of S 5 and folded string rotating in AdS 5. In the first case we clarify the general structure of the sigma model perturbation theory for the energy of string states beyond the one-loop order (related to the plane-wave limit). In the second case we argue that the large spin limit of the expression for the ground-state energy (i.e. for the dimension of the corresponding minimal twist gauge theory operator) has the form S + f(λ) ln S to all orders in the [Formula: see text] expansion, in agreement with the AdS/CFT duality. We also suggest the extension of the semiclassical approach to near-conformal (near-AdS) cases on the example of the fractional D3-brane on conifold background.
SOLITONS FOR THE FUZZY SPHERE FROM THE MATRIX MODEL
Authors: VALTANCOLI P.
Published: March 2003

Recently we have introduced a matrix model depending on two coupling constants g2 and λ, which contains the fuzzy sphere as a background; to obtain the classical limit g2 must depend on N in a precise way. In this paper we show how to obtain the classical solitons of the N → ∞ limit imposing the development [Formula: see text]; as a consequence at finite N one obtains a noncommutative version of the solitons for the fuzzy sphere.
CHAOTIC ROTATIONS OF AN ASYMMETRIC BODY WITH TIME-DEPENDENT MOMENTS OF INERTIA AND VISCOUS DRAG
Authors: IÑARREA M. , LANCHARES V. , ROTHOS V. M. , SALAS J. P.
Published: March 2003

We study the dynamics of a rotating asymmetric body under the influence of an aerodynamic drag. We assume that the drag torque is proportional to the angular velocity of the body. Also we suppose that one of the moments of inertia of the body is a periodic function of time and that the center of mass of the body is not modified. Under these assumptions, we show that the system exhibits a transient chaotic behavior by means of a higher dimensional generalization of the Melnikov's method. This method give us an analytical criterion for heteroclinic chaos in terms of the system parameters. These analytical results are confirmed by computer numerical simulations of the system rotations.
Weighted Deductive Parsing and Knuth's Algorithm
Authors: Nederhof Mark-Jan
Published: March 2003

We discuss weighted deductive parsing and consider the problem of finding the derivation with the lowest weight. We show that Knuth's generalization of Dijkstra's algorithm for the shortest-path problem offers a general method to solve this problem. Our approach is modular in the sense that Knuth's algorithm is formulated independently from the weighted deduction system.
The Economic and Environmental Implications of Centralized Stock Keeping
Authors: Matthews H. Scott , Hendrickson Chris T.
Published: March 2003

Recent changes to the management of inventory and warehousing methods have created significant changes in business processes. These changes have produced economic savings to firms from reduced handling of supplies. The system‐wide impacts of this shift in methods on overall cost and the environment are still unclear, however. Reductions in inventories can provide significant environmental savings. In this article, we analyze the changes in inventory control methods and assess the environmental and cost tradeoffs between increased trucking and more efficient centralized warehouses. We consider the case of consolidating the spare‐parts inventory at U.S. Department of Defense warehouses and discuss similarities to other existing businesses. The case suggests large economic and environmental benefits due to reductions in warehousing expenses, despite higher transportation costs.
Differentiation of stress, metabolism, communication, and defense responses following transplantation
Authors: Mueller Thomas F , Ma Chunyan , Lederer James A , Perkins David L
Published: March 2003

The biological complexity of allograft rejection and alloantigen-independent mechanisms is poorly understood. Therefore, we analyzed four components of the biological response following transplantation by global gene analysis. A comparative and kinetic approach was used to identify gene expression profiles. Biological processes were assigned to genes displaying the largest alterations in expression. Metabolism, stress response, and cell organization were the predominant, biological processes associated with ischemia and systemic stress. Innate and adaptive immune responses induced a transcriptional shift toward defense and cell communication. The kinetic analysis showed a shift from innate toward adaptive responses in the post-transplant course.
Gap-junctional coupling between neutrophils and endothelial cells: a novel modulator of transendothelial migration
Authors: Zahler Stefan , Hoffmann Anke , Gloe Torsten , Pohl Ulrich
Published: March 2003

Communication between leukocytes and endothelial cells is crucial for inflammatory reactions. Paracrine cross-talk and outside-in signaling (via adhesion molecules) have been characterized as communication pathways to date. As leukocytes and endothelial cells express connexins, we considered intercellular communication via gap junctions an intriguing additional concept. We found that gap-junctional coupling between neutrophils and endothelium occurred in a time-dependent, bidirectional manner and was facilitated by adhesion. After blockade of connexins, transmigration of neutrophils through the endothelial layer was enhanced, and the barrier function of cell monolayers was reduced during transmigration. Tumor necrosis factor α decreased coupling. In the presence of connexins, transmigration of neutrophils did not alter permeability. Thus, neutrophils couple to endothelium via gap junctions, functionally modulating transmigration and leakiness. Gap-junctional coupling may be a ovel way of leukocyte-endothelial communication.
β1/β3 integrin ligation is uncoupled from ERK1/ERK2 activation in cytotoxic T lymphocytes
Authors: Puente Lawrence G , Ostergaard Hanne L
Published: March 2003

β3 integrins mediate fibronectin binding and enhanced activation of cytotoxic T lymphocytes (CTL). The intracellular signals initiated by β3 integrins in lymphocytes are not well characterized, but in many cell types, β1 integrin ligation activates mitogen-activated protein (MAP) kinases. In the present study, we find that fibronectin can synergize with very low levels of CD3 stimulation to activate the extracellular signal-regulated kinase (ERK)1 and ERK2 MAP kinases but that fibronectin alone induces no detectable MAP kinase activation in CTL. Surprisingly, antibodies to β1 or β3 integrins were also unable to stimulate MAP kinase activation, suggesting that although β1 integrins are capable of stimulating MAP kinase activation in other cells, they cannot do so in CTL. In CTL, phosphorylation of proline-rich tyrosine kinase 2 downstream of integrin stimulation did not result in recruitment of the adaptor protein Grb2. Additionally, we examined the role of MAP kinases in regulating integrin-mediated adhesion. Anti-CD3-triggered adhesion to fibronectin was largely insensitive to the MAP kinase kinase inhibitor PD98059. Triggered cell-spreading on fibronectin was inhibited by PD98059 but not by U0126. In summary, ligation of β3 integrin by antibodies or fibronectin or of β1 integrin by monoclonal antibodies fails to activate ERK MAP kinases, but integrin ligation synergizes with T cell receptor stimulation upstream of MAP kinases.
Characterization of promoter elements directing Mona/Gads molecular adapter expression in T and myelomonocytic cells: involvement of the AML-1 transcription factor
Authors: Guyot B , Mouchiroud G
Published: March 2003

Monocytic adaptor (Mona, also called Gads) is a molecular adaptor implicated in T cell activation and macrophage differentiation. The objective of this study was to identify elements regulating specific expression of Mona/Gads in human T cell and myelomonocytic cell lines. We first confirmed that the −2000 to +150 genomic region relative to the Mona gene transcription start site is sufficient to direct specific reporter gene expression in T cell lines, Jurkat, and MOLT-4 and in the immature myeloid cell lines, KG1a and RC2A. Deletion analysis and electrophoresis mobility shift assay identified several cis regulatory elements: overlapping initiator sequences, one interferon response factor-2 (IRF-2)-binding site at position −154, one GC box recognized by Sp1 and Sp3 at position −52, and two acute myeloid leukemia (AML)-1 binding sites at positions −70 and −13. Site-directed mutagenesis experiments indicated a key role of AML-1 for driving Mona expression in T cells and myeloid cells, and involvement of Sp1/Sp3 and IRF-2 transcription factors to modulate Mona expression in a cell-specific manner.
Actin cytoskeletal dynamics in T lymphocyte activation and migration
Authors: Samstag Yvonne , Eibert Sybille M , Klemke Martin , Wabnitz Guido H
Published: March 2003

Dynamic rearrangements of the actin cytoskeleton are crucial for the function of numerous cellular elements including T lymphocytes. They are required for migration of T lymphocytes through the body to scan for the presence of antigens, as well as for the formation and stabilization of the immunological synapse at the interface between antigen-presenting cells and T lymphocytes. Supramolecular activation clusters within the immunological synapse play an important role for the initiation of T cell responses and for the execution of T cell effector functions. In addition to the T cell receptor/CD3 induced actin nucleation via Wasp/Arp2/3-activation, signals through accessory receptors of the T cell (i.e., costimulation) regulate actin cytoskeletal dynamics. In this regard, the actin-binding proteins cofilin and L-plastin represent prominent candidates linking accessory receptor stimulation to the rearrangement of the actin cytoskeleton. Cofilin enhances actin polymerization via its actin-severing activity, and as a long-lasting effect, cofilin generates novel actin monomers through F-actin depolymerization. L-plastin stabilizes acin filament structures by means of its actin-bundling activity.
Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response
Authors: Charbonnier Anne-Sophie , Hammad Hamida , Gosset Philippe , Stewart Geoffrey A , Alkan Sefik , Tonnel André-Bernard , Pestel Joël
Published: March 2003

Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4+ T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-γhigh/IL-4low] and Der p 1-pulsed P-DC, a Th2 profile (IFN-γlow/IL-4high). In healthy donors, no T cell polarization (IFN-γlow/IL-4low) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.
Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected mice and restrains their fratricide: role of Fas ligand down-regulation and MHC class II-transactivator up-regulation
Authors: Acosta Rodriguez E V , Zuñiga E , Montes C L , Gruppi A
Published: March 2003

In the present work, we demonstrate that interleukin (IL)-4 is able to rescue B cells from Trypanosoma cruzi-infected mice, counteracting the strong apoptotic signals that these cells received in vivo. We have observed that IL-4 restrains the apoptosis of immunoglobulin (Ig)M+ and IgG+ B cells from infected and normal mice without inducing them to proliferate. In addition, IL-4 does not modify the quantity or quality of the antibodies secreted by B cells from infected mice, as it blocks their terminal differentiation to plasma cells and favors memory pathway. It is interesting that the protective effect of IL-4 over B cells from infected mice is mediated, at least partly, by the down-regulation of Fas ligand (FasL) expression, which leads to interference in the apoptosis executed by these B cells through the Fas/FasL death pathway. Accordingly, a marked up-regulation of the “FasL gene repressor” class II transactivator was observed, suggesting that this would be one mechanism underlying the IL-4-mediated FasL down-regulation.
Cell type-dependent activation of 5-lipoxygenase by arachidonic acid
Authors: Bürkert Eva , Szellas Dagmar , Rådmark Olof , Steinhilber Dieter , Werz Oliver
Published: March 2003

5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes. We show that stimulation of polymorphonuclear leukocytes (PMNL), rat basophilic leukemia (RBL)-1, or transfected HeLa cells with arachidonic acid (AA) caused prominent 5-LO product formation that coincided with the activity of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase. 5-LO product formation in AA-stimulated PMNL and RBL-1 cells was independent of Ca2+. However, in HeLa cells expressing a 5-LO mutant lacking potential 5-LO phosphorylation sites, removal of Ca2+ caused a prominent loss of 5-LO activity. For Mono Mac 6 (MM6) cells, A failed to activate ERKs, and AA-induced 5-LO product formation was only minute. Also, activation of ERKs by phorbol esters did not lead to prominent 5-LO product synthesis. Instead, 5-LO activation in MM6 cells required Ca2+ or alternative signaling pathways induced by hyperosmotic stress. In summary, mechanisms for activation of 5-LO differ considerably between cell types.
Human immunodeficiency virus type 1 (HIV-1) induces activation of multiple STATs in CD4+ cells of lymphocyte or monocyte/macrophage lineages
Authors: Kohler James J , Tuttle Daniel L , Coberley Carter R , Sleasman John W , Goodenow Maureen M
Published: March 2003

Human immunodeficiency virus type 1 (HIV-1) impacts the activation state of multiple lineages of hematopoietic cells. Chronic HIV-1 infection among individuals with progressive disease can be associated with increased levels of activated signal transducers and activators of transcription (STATs) in peripheral blood mononuclear cells. To investigate interactions between HIV-1 and CD4+ cells, activated, phosphorylated STAT proteins in nuclear extracts from lymphocytic and promonocytic cell lines as well as primary monocyte-derived macrophages were measured. Levels of activated STATs increased six- to tenfold in HUT78 and U937 cells within 2 h following exposure to virions. The response to virus was dose-dependent, but kinetics of activation was delayed relative to interleukin-2 or interferon-γ. Activation of STAT1, STAT3, and STAT5 occurred with diverse viral envelope proteins, independent of coreceptor use or viral replication. Envelope-deficient virions had no effect on STAT activation. Monoclonal antibody engagement of CD4 identified a novel role for CD4 as a mediator in the activation of multiple STATs. Results provide a model for HIV-1 pathogenesis in infected and noninfected hematopoietic cells.
Regulation of lymphocyte-mediated killing by GTP-binding proteins
Authors: Khurana Dianne , Leibson Paul J
Published: March 2003

Exocytosis of granules containing apoptosis-inducing proteins is one mechanism of target cell killing by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Granules containing perforin and granzymes are redistributed to the area of cell contact initiated by specific interactions between surface ligands on a target cell and receptors on an effector lymphocyte. The formation of a stable conjugate between a cytotoxic lymphocyte and its potential target cell, followed by the directed delivery of granule components to the target cell are prerequisites of lymphocyte-mediated killing. Critical to understanding the development of cytotoxic function by CTLs and NK cells is the delineation of the second messenger pathways that specifically control the reorganization of the actin cytoskeleton during cell-mediated cytotoxicity. The low molecular weight guanosine 5′-triphosphate-binding proteins of the Rho family play a central role in these regulatory events controlling cytotoxic lymphocyte activation.
Differential recruitment of α2β1 and α4β1 integrins to lipid rafts in Jurkat T lymphocytes exposed to collagen type IV and fibronectin
Authors: Holleran Brian J , Barbar Élie , Payet Marcel D , Dupuis Gilles
Published: March 2003

Collagen type IV (CnIV) and fibronectin (Fn) were used as ligands to study the distribution of α2β1 and α4β1 integrins in low-density, detergent-resistant microdomains (DRM) of Jurkat lymphocytes. CnIV-coated microspheres induced (optical trapping) the redistribution of GM1-associated fluorecence from the cell periphery to the area of contact. This was not observed in cells treated with β-methyl cyclodextrin (MCD). Fn- or bovine serum albumin-coated microspheres did not modify the peripheral distribution of fluorescence. These observations were confirmed by confocal microscopy. Western blot analysis of cells exposed to surfaces coated with CnIV revealed that the α2-subunit was initially present at low levels in DRM, became strongly associated after 40 min, and returned to basal levels after 75 min. Fn induced a slight recruitment of the β1-integrin α4-subunit in DRM after 5 and 10 min, followed by a return to basal levels. Neither CnIV nor Fn triggered significant changes in the distribution of the β1-subunit in DRM. Fn- and CnIV-coated microspheres or surfaces coated with these ligands triggered a MCD-sensitive mobilization of Ca2+. MCD did not alter the state of the Ca2+ reserves. The differential distributions of the α2β1 and α4β1 integrins in DRM may provide one additional step in the regulation of outside-in signaling involving these integrins.
Synergism of nitric oxide and maturation signals on human dendritic cells occurs through a cyclic GMP-dependent pathway
Authors: Paolucci Clara , Burastero Samuele E , Rovere-Querini Patrizia , De Palma Clara , Falcone Sestina , Perrotta Cristiana , Capobianco Annalisa , Manfredi Angelo A , Clementi Emilio
Published: March 2003

Nitric oxide (NO), generated by phagocytes at inflammation sites, contributes to regulate immune responses through autocrine and paracrine actions on bystander cells. Among the latter are dendritic cells (DCs). Little is known about regulation of DC function by NO, especially in the human system. We exposed human monocyte-derived DCs to the NO donor (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium-1,2 diolate (DETA-NO) during their maturation process induced by treatment with tumor necrosis factor α or lipopolysaccharide or by CD40 activation. We report here that after exposure to DETA-NO, DCs exhibit a significantly increased ability to activate T lymphocytes stimulated by mycobacterial antigens, Staphylococcus aureus Cowen strain B, allo-antigens, or cross-linking of the CD3–T cell receptor complex. This effect persists after removal of DETA-NO, depends on the generation of cyclic guanosine 5′-monophosphate, and is a result of enhanced release by DCs of soluble factors, in particular interleukin (IL)-12. This modulation of DC function is a result of a synergism between NO and the various maturation stimuli, as neither enhanced T cell activation nor IL-12 release was observed after DC exposure to DETA-NO only. These results provide the first evidence that NO acts as a cosignaling molecule regulating human DC response to maturation stimuli.
CBP Recruitment and Histone Acetylation in Differential Gene Induction by Glucocorticoids and Progestins
Authors: Lambert James R. , Nordeen Steven K.
Published: March 2003

We have analyzed histone acetylation at the steroid-responsive mouse mammary tumor virus (MMTV) promoter in five separate cell lines that express functional glucocorticoid and/or progesterone receptors. Chromatin immunoprecipitation assays reveal that glucocorticoid and progesterone receptors bind the MMTV promoter after hormone addition but that receptor binding is not associated with an increase in acetylation of histone H3 or H4. We have, however, found one exception to this rule. Previously we described a cell line [T47D(C&L)] that displayed a remarkable differential induction of MMTV by glucocorticoids and progestins. At one chromosomal locus (MMTV-luciferase), MMTV is preferentially induced by glucocorticoids, whereas at another locus within the same cell (MMTV-CAT), MMTV is activated by both glucocorticoids and progestins. Here we show that the glucocorticoid-mediated induction of MMTV-luciferase is accompanied by increased recruitment of CBP to the promoter and increased histone H3 and H4 acetylation, whereas the hormonal induction of MMTV-CAT in the same cell exhibits a more modest CBP recruitment without any increase in histone acetylation. These studies suggest that increased histone acetylation may serve a potentiating function for MMTV promoter activation at certain loci. However, increased histone acetylation is not requisite for steroid-mediated induction of transcription at all genes.
Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears ofFoxi1null mutant mice
Authors: Hulander Malin , Kiernan Amy E. , Blomqvist Sandra Rodrigo , Carlsson Peter , Samuelsson Emma-Johanna , Johansson Bengt R. , Steel Karen P. , Enerbäck Sven
Published: March 2003

Mice that lack the winged helix/forkhead gene Foxi1 (also known asFkh10) are deaf and display shaker/waltzer behavior, an indication of disturbed balance. While Foxi1 is expressed in the entire otic vesicle at E9.5, it becomes gradually restricted to the endolymphatic duct/sac epithelium and at E16.5 Foxi1 expression in the inner ear is confined to this epithelium. Histological sections, paintfill experiments and whole-mount hybridizations reveal no abnormality in inner ear development ofFoxi1-/- mice before E13.5. Between E13.5 and E16.5 the membranous labyrinth of inner ears from null mutants starts to expand as can be seen in histological sections, paint-fill experiments and three-dimensional reconstruction. Postnatally, inner ears of Foxi1-/- mice are extremely expanded, and large irregular cavities, compressing the cerebellum and the otherwise normal middle ear, have replaced the delicate compartments of the wild-type inner ear. This phenotype resembles that of the human sensorineural deafness syndrome Pendred syndrome, caused by mutations in the PDS gene. In situ hybridization of Foxi1-/-endolymphatic duct/sac epithelium shows a complete lack of the transcript encoding the chloride/iodide transporter pendrin. Based on this, we would like to suggest that Foxi1 is an upstream regulator of pendrin and that the phenotype seen in Foxi1 null mice is, at least in part, due to defective pendrin-mediated chloride ion resorption in the endolymphatic duct/sac epithelium. We show that this regulation could be mediated by absence of a specific endolymphatic cell type — FORE (forkhead related) cells— expressing Foxi1, Pds, Coch and Jag1. Thus,mutations in FOXI1 could prove to cause a Pendred syndrome-like human deafness.
Informed consent for septal surgery: the evidence-base
Authors: Bateman N. D. , Woolford T. J.
Published: March 2003

Informed consent is becoming an increasingly important issue in patient care. Inherent in this is the ability to accurately inform patients of the risks and complications involved in surgery. Nasal septal surgery is commonly performed by otolaryngologists and although often considered routine has a number of recognized complications that can have a significant effect on life quality. We carried out a review of the literature over the last 25 years and reviewed studies quoting rates of complications after septoplasty and submucous resection (SMR) using strictly applied criteria for study inclusion. There was a paucity of prospective data, especially for the cosmetic effects of septal surgery. Rates of septal perforation were two to eight per cent for SMR and 1.6–5.4 per cent for septoplasty. The incidence of cosmetic deformity was low for both procedures zero to one per cent. More well-designed studies are required to augment the current evidence base. While this does not replace the need for surgeons to audit their own results it provides evidence-based information to assist in the process of informed consent.
Analytical and clinical evaluation of CYFRA 21-1 by electrochemiluminescent immunoassay in head and neck squamous cell carcinoma
Authors: Deng Yan Fei , Chen Ping , Lin Yong Zhi , Le Jia Zhen , Wu Xiao Li , Yu Ming Qiang , Zhuang Pei Yun , Gao Ming Hua
Published: March 2003

This paper attempts to evaluate the clinical usefulness of CYFRA 21-1 as a serum tumour marker in patients with head and neck squamous cell carcinoma (HNSCC).

The serum concentration of CYFRA 21-1 was measured utilizing a new electrochemiluminescent immunoassay (ECLIA) in 142 patients with HNSCC before and after treatment, 68 patients with benign tumours of the head and neck, and 50 healthy controls.

Serum levels of CYFRA 21-1 in patients with HNSCC were significantly higher than those of benign tumours and healthy controls (p < 0.001). The diagnostic sensitivity and specificity of CYFRA 21-1 for HNSCC were 62 per cent and 100 per cent, respectively. The positive rates of CYFRA 21-1 increased with progression of HNSCC, serum CYFRA 21-1 levels were related to the tumour stage expressed by primary tumour (T) and nodal status (N) (p < 0.001), but not related to patient age, gender, smoking and drinking habit, or histopathological grade (p > 0.05). Post-treatment levels of CYFRA 21-1 in HNSCC decreased significantly (p < 0.001). Among 38 patients with clinical or radiological evidence of a recurrence during follow-up, 78.9 per cent (30 of 38) showed an increase in CYFRA 21-1.

The analytical ECLIA performance for serum CYFRA 21-1 provides a new means of clinical assessment for HNSCC. The results of ECLIA suggest that the serum marker CYFRA 21-1 is valuable not only for diagnosis but also for close monitoring of patients with HNSCC.
Early diagnosis and stage-adapted treatment of Wegener’s granulomatosis
Authors: Cadoni G. , Agostino S. , Campobasso E. , Vulpiani P. , Manna R. , Galli J.
Published: March 2003

A case of Wegener’s granulomatosis (WG) presenting with hearing loss and right facial nerve palsy is reported. The definitive diagnosis was based upon clinical data and serum cANCA and AECA detection. Early assessment of WG prevented surgical facial nerve decompression to treat a chronic otitis media complication. Immunosuppressive therapy with steroids, cyclophosphamide and methotrexate was required for relief of clinical symptoms and cANCA negativity as an expression of disease remission. The effectiveness of co-trimoxazole for preventing relapses of WG is discussed.
Early radiation-induced malignant fibrous histiocytoma of the oral cavity
Authors: Wiesmiller Kerstin , Barth Thomas F. E. , Gronau Silke
Published: March 2003

With an incidence of less than 0.3 per cent, post-radiation sarcomas are rare malignant neoplasms with a very poor prognosis. On average, they occur after a latency period of at least 15 years following radiation therapy with doses ranging from 24 to 80 Gy. We present the case of a post-irradiation malignant fibrous histiocytoma (MFH) on the floor of the mouth in a 79-year-old male patient arising only five and a half years after radiation therapy. The primary tumour was classified as a well differentiated squamous cell carcinoma of the right rim of the tongue. Primary therapy was surgical resection of the tumour and post-operative radiation with 50 Gy. Five and a half years later, the patient developed a rapidly progressing MFH within the field of radiation.
Cardiorespiratory Events Recorded on Home Monitors
Authors: Ramanathan Rangasamy , Corwin Michael J. , Hunt Carl E. , Lister George , Tinsley Larry R. , Baird Terry , Silvestri Jean M. , Crowell David H. , Hufford David , Martin Richard J. , Neuman Michael R. , Weese-Mayer Debra E. , Cupples L. Adrienne , Peucker Mark , Willinger Marian , Keens Thomas G. ,   for The Collaborative Home Infant Monitoring Evaluation (CHIME) Study Group
Published: March 2003

Context

Home monitors designed to identify cardiorespiratory events are frequently used in infants at increased risk for sudden infant death syndrome (SIDS), but the efficacy of such devices for this use is unproven.

Objective

To test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants.

Design

Longitudinal cohort study conducted from May 1994 through February 1998.

Setting

Five metropolitan medical centers in the United States.

Participants

A total of 1079 infants (classified as healthy term infants and 6 groups of those at risk for SIDS) who, during the first 6 months after birth, were observed with home cardiorespiratory monitors using respiratory inductance plethysmography to detect apnea and obstructed breathing.

Main Outcome Measures

Occurrence of cardiorespiratory events that exceeded predefined conventional and extreme thresholds as recorded by the monitors.

Results

During 718 358 hours of home monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445 infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of those events with apnea, 70% included at least 3 obstructed breaths. The frequency of at least 1 extreme event was similar in term infants in all groups, but preterm infants were at increased risk of extreme events until 43 weeks' postconceptional age.

Conclusions

In this study, conventional events are quite common, even in healthy term infants. Extreme events were common only in preterm infants, and their timing suggests that they are not likely to be immediate precursors to SIDS. The high frequency of obstructed breathing in study participants would likely preclude detection of many events by conventional techniques. These data should be important for designing future monitors and determining if an infant is likely to be at risk for a cardiorespiratory event.
Management of Chronic Tension-Type Headache With Tricyclic Antidepressant Medication, Stress Management Therapy, and Their Combination
Authors: Holroyd Kenneth A. , O'Donnell Francis J. , Stensland Michael , Lipchik Gay L. , Cordingley Gary E. , Carlson Bruce W.
Published: March 2003

Context

Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects.

Objective

To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches.

Design and Setting

Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio.

Participants

Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo).

Interventions

Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53).

Main Outcome Measures

Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating ≥5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group.

Results

Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (≥50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P = .006), stress management therapy (35%; P = .003), or placebo (29%; P = .001). On other measures the combined therapy and its 2 component therapies produced similar outcomes.

Conclusions

Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.
Prevalence of C282Y and H63D Mutations in the Hemochromatosis (HFE) Gene in the United States
Authors: Steinberg Karen K. , Cogswell Mary E. , Chang Joy C. , Caudill Samuel P. , McQuillan Geraldine M. , Bowman Barbara A. , Grummer-Strawn Laurence M. , Sampson Eric J. , Khoury Muin J. , Gallagher Margaret L.
Published: March 2003

Context

Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening.

Objective

To estimate the prevalence of the HFE mutations C282Y and H63D in the US population.

Design

Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994.

Setting and Participants

Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis.

Main Outcome Measures

Estimates of the prevalence of C282Y and H63D mutations.

Results

The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation.

Conclusions

Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.
The Origins, History, and Design of the Resident Match
Authors: Roth Alvin E.
Published: March 2003

In the early 1900s, competition among hospitals for interns and among medical students for good internships led to increasingly early offers of internships to students. By the 1940s, appointments were often made as early as the beginning of the junior year of medical school. Hospitals thus had little information about students' performance, and students frequently had to make a final decision to accept or reject an offer without knowing which other offers might be forthcoming. From 1945 through 1951, efforts were made to enforce a uniform date for accepting offers. However, students were still faced with offers having very short deadlines, compelling them to accept or reject offers without knowing what other offers might be forthcoming. Hospitals often had to scramble for available students, since if an offer was rejected, it was often too late for them to reach their next preferred candidate. A centralized clearinghouse was thus developed as a way of alleviating this chaos and allowing a larger role to the preferences of both students and hospitals. This evolved into the current matching program, whose algorithm continues to be updated to take account of changing needs of applicants, such as growth in the number of couples who seek 2 positions in the same vicinity.
Maternal Immunity and Prevention of Congenital Cytomegalovirus Infection
Authors: Fowler Karen B. , Stagno Sergio , Pass Robert F.
Published: March 2003

Context

Vaccine development to prevent congenital cytomegalovirus (CMV) infection has been impeded by the uncertainty over whether maternal immunity protects the fetus.

Objective

To determine whether the presence of maternal antibodies to CMV significantly reduces the risk of congenital CMV infection in future pregnancies.

Design, Setting, and Participants

Cohort study of 3461 multiparous women from a population with a high rate of congenital CMV infection who delivered newborns screened for congenital CMV infection between 1993 and 1998, and whose cord serum specimen from a previous delivery could be retrieved and tested for antibody to CMV.

Main Outcome Measure

Congenital CMV infection according to maternal immune status, age, race, parity, and socioeconomic status.

Results

Of 604 newborns born to initially seronegative mothers, congenital CMV infection occurred in 18 (3.0%). In contrast, of 2857 newborns born to immune mothers, congenital CMV infection occurred in 29 (1.0%) Two factors, preconception maternal immunity (adjusted risk ratio, 0.31; 95% confidence interval, 0.17-0.58) and maternal age of 25 years or older (adjusted risk ratio, 0.19; 95% confidence interval, 0.07-0.49), were highly protective against congenital CMV infection. No other factors were associated with a reduction in the risk of congenital CMV infection.

Conclusion

Naturally acquired immunity results in a 69% reduction in the risk of congenital CMV infection in future pregnancies.
Alcohol Consumption and Expenditures for Underage Drinking and Adult Excessive Drinking
Authors: Foster Susan E. , Vaughan Roger D. , Foster William H. , Califano Joseph A.
Published: March 2003

Context

Although estimates of the amount and proportion of alcohol consumed by underage and adult drinkers have been reported, more accurate estimates are possible and the economic impact has not been explored.

Objectives

To provide accurate estimates of underage and adult excessive drinking and to describe consumer expenditures linked to underage and adult excessive drinking.

Design and Setting

Information was obtained from national data sets, including 1999 versions of the National Household Survey of Drug Abuse, the Youth Risk Behavior Survey (YRBS), the Behavior Risk Factor Surveillance System (BRFSS), 2000 US Census, and national data on consumption and consumer expenditures for alcohol, published by Adams Business Research.

Participants

A total of 217 192 persons aged 12 years or older across 3 data sources.

Main Outcome Measures

Amount as a proportion of total alcohol consumed and proportion of consumer expenditures on alcohol among underage (12-20 years) and adult excessive (≥21 years) drinkers.

Results

The proportion of 12- to 20-year-olds who drink was estimated to be 50.0% using data from the YRBS; the proportion of adults aged 21 or older who drink was estimated to be 52.8% using data from the BRFSS. The estimated total number of drinks consumed per month was 4.21 billion; underage drinkers consumed 19.7% of this total. The amount of adult drinking that was excessive (>2 drinks per day) was 30.4%. Consumer expenditure on alcohol in the United States in 1999 was $116.2 billion; of that, $22.5 billion was attributed to underage drinking and $34.4 billion was attributed to adult excessive drinking.

Conclusion

These data suggest that underage drinkers and adult excessive drinkers are responsible for 50.1% of alcohol consumption and 48.9% of consumer expenditure.
Impact of Quality Improvement Efforts on Race and Sex Disparities in Hemodialysis
Authors: Sehgal Ashwini R.
Published: March 2003

Context

By improving the process of care, quality improvement efforts have the potential to reduce race and sex disparities. However, little is known about whether reductions actually occur. National quality improvement activities targeting hemodialysis patients provide an opportunity to examine this issue.

Objective

To determine the effect of quality improvement efforts on race and sex disparities among hemodialysis patients.

Design, Setting, and Subjects

Longitudinal study of 58 700 randomly selected hemodialysis patients from throughout the United States in 1993 through 2000.

Intervention

Medicare-funded quality improvement project involving monitoring of patient outcomes, feedback of performance data, and education of clinicians at dialysis centers.

Main Outcome Measures

Changes in hemodialysis dose (Kt/V), anemia management (hemoglobin level), and nutritional status (albumin level).

Results

The proportion of all patients with an adequate hemodialysis dose increased 2-fold. In 1993, 46% of white patients and 36% of black patients received an adequate hemodialysis dose compared with 2000 when the proportions were 87% and 84%, respectively. Thus, the gap between white and black patients decreased from 10% to 3% (P<.001). The gap between female and male patients decreased from 23% to 9% over the same period (P = .008). The proportion of all patients with adequate hemoglobin levels increased 3-fold. The proportion of all patients with adequate albumin levels remained unchanged. Race and sex disparities in anemia management and nutritional status did not change significantly.

Conclusions

Quality improvement efforts have a variable impact on race and sex disparities in health outcomes. Further work is needed to determine how quality improvement methods can be targeted to reduce health disparities.