bluuebunny/crossref_metadata_2025 huggingface dataset:
Human sperm aneuploidy after exposure to pesticides
Authors: Smith Jena L. , Garry Vincent F. , Rademaker Alfred W. , Martin Renée H.
Published: January 2004

This study examined the effect of paternal environmental exposure to pesticides on the frequency of aneuploidy in human sperm. To determine if the chromosome number in germ cells was altered by paternal exposure, multicolor fluorescence in situ hybridization (FISH) analysis was utilized to measure aneuploidy frequencies in the sperm of 40 men (20 exposed, 20 controls). Samples were coded for “blind analysis” to eliminate scorer bias. Aneuploidy and diploidy frequencies were assessed for chromosomes 13, 21, X, and Y. A minimum of 10,000 sperm was scored per donor per chromosome probe with a total of 809,935 sperm scored. Hybridization efficiency was 99%. There were no significant differences in aneuploidy or diploidy frequencies between exposed and control groups, suggesting that the pesticides did not increase the risk of numerical chromosomal abnormalities in these men. Mol. Reprod. Dev. 67: 353–359, 2004. © 2004 Wiley‐Liss, Inc.
Tektin3 encodes an evolutionarily conserved putative testicular microtubules‐related protein expressed preferentially in male germ cells
Authors: Roy Angshumoy , Yan Wei , Burns Kathleen H. , Matzuk Martin M.
Published: January 2004

Tektins are microtubule‐associated cytoskeletal proteins that are expressed primarily in the male germ cell‐lineage in centrioles and basal bodies and within ciliary and flagellar doublet microtubules. They are proposed to be important for axonemal architecture and microtubule stability in the sperm tail and in other ciliated and flagellar structures. Using an in silico (electronic database) subtractive approach to identify germ cell‐specific genes in vertebrates, we isolated a new member of the Tektin gene family from mice, Tektin3. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Northern blot analyses confirm that Tektin3 encodes a 1.7 kb transcript detectable preferentially in the testes of adult mice. In situ hybridization analysis in the testes revealed Tektin3 mRNA expression exclusively in late pachytene spermatocytes and early round spermatids. The putative TEKTIN3 protein shares 83.5% overall sequence identity with the human ortholog and includes a fully conserved carboxy terminal nonapeptide signature sequence present in all TEKTIN family members. In addition, using database mining, highly conserved TEKTIN3 orthologs were identified in puffer fish (Fugu rubripes) and rats (Rattus norvegicus) which shared 60.9 and 91.4% identity, respectively, with mouse TEKTIN3. The Tekt3 gene maps to murine chromosome 11 in a region that is syntenic to the human 17p12 chromosomal region containing the human TEKTIN3 gene. Our studies demonstrate that TEKTIN3 is a novel evolutionarily conserved male germ cell‐enriched protein and suggest that it might perform important roles in male reproductive development and physiology. Mol. Reprod. Dev. 67: 295–302, 2004. © 2004 Wiley‐Liss, Inc.
Stage‐specific and tissue‐specific expression characteristics of differentially expressed genes during mouse spermatogenesis
Authors: Guo Rui , Yu Zuoren , Guan Jikui , Ge Yehua , Ma Jing , Li Sai , Wang Shali , Xue Shepu , Han Daishu
Published: January 2004

Spermatogenesis occurs in successive mitotic, meiotic, and post‐meiotic phase, and involves a number of unique processes including meiosis and dramatic morphological changes. The unique differentiation mechanisms of spermatogenesis suggest the existence of germ‐cell‐specific molecules. The most straight forward strategy to elucidate differentiation mechanisms is to identify and characterize differentiation‐specific molecules and their associated genes in germ cells. However, only a few genes specifically involved in spermatogenesis have been studied. In the present study, six different types of spermatogenic cells (primitive type A spermatogonia, type B spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, round spermatids, and elongating spermatids) were isolated from Balb/c mice testes using velocity sedimentation and Atlas cDNA arrays containing 1,176 known mouse genes were used to determine the gene expression profiles of the spermatogenic cells. The expression of 260 genes were detected in six different stages of spermatogenic cells and a number of genes showed differential expression. The 23 differentially expressed genes were further analysed by reverse transcription polymerase chain reaction (RT‐PCR) for their stage‐specific and tissue‐specific expression characteristics. Based on the results of RT‐PCR, six genes highly express in both primitive type A and type B spermatogonia, four genes up‐regulate in type B spermatogonia, two genes up‐regulate in spermatocytes, two genes up‐regulate in spermatids, three genes express constantly from primitive A spermatogonia to elongating spermatids, two genes express constantly from primitive A spermatogonia to round spermatids, two genes do not change in their expression during spermatogenesis, two genes can be detected highly in adult testis, but are undetectable in spermatogenic cells. The tissue‐specific expression characteristics of the 23 genes showed that some of them specifically expressed in testes or other tissues. These data provide new information for further studies into spermatogenesis‐related genes and may lead to the identification of genes with potential relevance to the differentiation of spermatogenic cells. In addition, some of these genes could be considered to be used as the molecular markers for different stages of spermatogenic cells. Mol. Reprod. Dev. 67: 264–272, 2004. © 2004 Wiley‐Liss, Inc.
Aromatase inhibitor induces complete sex change in the protogynous honeycomb grouper (Epinephelus merra)
Authors: Bhandari Ramji Kumar , Higa Mikihiko , Nakamura Shigeo , Nakamura Masaru
Published: January 2004

The protogynous hermaphrodite fish change sex from female to male at the certain stages of life cycle. The endocrine mechanisms involved in gonadal restructuring throughout protogynous sex change are not clearly understood. In the present study, we implanted maturing female honeycomb groupers with nonsteroidal aromatase inhibitor (AI), Fadrozole (0, 1, and 10 mg/fish) and examined changes in gonadal structures and serum levels of sex steroid hormones 2½ months after implantation. The ovaries of control females had oocytes undergoing active vitellogenesis, whereas AI caused females to develop into functional males. These males had testes, which were indistinguishable in structure from those of normal males, but bigger in size, and completed all stages of spermatogenesis including accumulation of large amount of sperm in the seminiferous tubules. AI significantly reduced the serum levels of estradiol‐17β (E2) and increased levels of testosterone (T), 11‐ketotestosterone (11‐KT), and 17α, 20β‐dihydroxy‐4‐pregnen‐3‐one (DHP). Further, AI suppressed in vitro production of E2, and stimulated the production of T and 11‐KT in the ovarian fragments of mature female. In the honeycomb grouper, suppression of both in vitro and in vivo production of E2 and degeneration of oocytes by AI suggests that AI induces complete sex change through inhibition of estrogen biosynthesis, and perhaps, subsequent induction of androgen function. Mol. Reprod. Dev. 67: 303–307, 2004. © 2004 Wiley‐Liss, Inc.
Rapid PKA‐catalysed phosphorylation of boar sperm proteins induced by the capacitating agent bicarbonate
Authors: Harrison R.A.P.
Published: January 2004

In boar spermatozoa, the capacitating agent bicarbonate has been shown to induce rapid changes both in plasma membrane lipid architecture and in motility; in each case, a PKA‐dependent pathway is involved. Early bicarbonate‐induced changes in protein phosphorylation were probed using a commercial antibody against the phosphorylated form of the consensus substrate site for cyclic AMP‐dependent protein kinase. The antibody detected relatively few bands in sperm extracts, of which only a small number showed incubation‐dependent changes. While the quantitative response varied between boar ejaculates, in general terms bicarbonate induced phosphorylation increases in bands of 96, 64, and 59 kDa within 80 sec. The changes reached a maximum after about 160 sec, declined somewhat thereafter, and then increased again slowly as incubation progressed further (up to 21 min). The bicarbonate‐induced increases were strongly dependent on the presence of BSA in the incubation medium. They were inhibited by H89 (PKA inhibitor) but not by GF (PKC inhibitor), and were enhanced by papaverine (phosphodiesterase inhibitor) and by calyculin (protein phosphatase inhibitor). The cyclic AMP analogue cBIMPS was able to mimic bicarbonate action though its effect was less dramatic. Stearated Ht31, a permeable inhibitor of PKA's binding to A‐kinase anchoring protein, did not affect either the intensity or the specificity of the bicarbonate‐induced phosphorylation changes, though it blocked motility entirely. Immunocytochemical studies revealed marked bicarbonate‐dependent phosphorylation changes in the post‐acrosomal region of the head and in the neck, midpiece, and anterior regions of the tail. Fractionation of stimulated spermatozoa showed that all bands detectable with the antibody were bound to heads and to midpieces and associated large tail fragments; no bands were detected in either small tail or membrane fragments or in the cytoplasmic fraction. Differential extraction of the midpiece/large tail fraction revealed two protein bands with closely similar electrophoretic mobilities to the 96‐ and 59‐kDa phosphorylated bands; MALDI‐TOF analyses of these bands revealed both to be members of the Odf2 family. Mol. Reprod. Dev. 67: 337–352, 2004. © 2004 Wiley‐Liss, Inc.
Enhancement of prostacyclin synthesis at the beginning of formation of caprine corpora lutea
Authors: Kawate Noritoshi , Tsuji Makoto , Tamada Hiromichi , Inaba Toshio , Sawada Tsutomu
Published: January 2004

We examined changes in the levels of prostacyclin (PGI2) synthase mRNA and 6‐keto‐PGF1α, a stable metabolite of PGI2, in the caprine corpus luteum (CL) during its development and subsequent maintenance. We also looked at the effects of a potent GnRH antagonist (GA), which is known to suppress the release of luteinizing hormone (LH), on the PGI2 synthase mRNA level and the 6‐keto‐PGF1α content during CL development. Goats were divided into a control group (n = 12) and a GA‐treated group (n = 6). They were treated with saline or GA (50 μg/kg, s.c.) on days 0 (day of ovulation), 4, and 8 (control only), and the CL were collected from a subset of goats (n = 3 for each day) on days 0 (no saline), 4, 8, or 14 (control only). Ribonuclease protection assay was performed to quantify the mRNA in the CL using specific cRNA probes generated by RT‐PCR and in vitro transcription. The 6‐keto‐PGF1α content in the CL was measured by radioimmunoassay. The level of PGI2 synthase mRNA and the 6‐keto‐PGF1α content in the CL in the control group decreased from day 0 to day 4 (P < 0.01), and did not change thereafter from day 4 to day 14. Levels of PGI2 synthase mRNA and 6‐keto‐PGF1α content in the CL on days 4 and 8 were not affected by treatment with GA. These results suggest that PGI2 synthesis is regulated upward at the beginning of caprine CL formation; this may play a role in initiating CL development. This study also suggests that changes of PGI2 synthesis during CL development are probably not regulated by LH. Mol. Reprod. Dev. 67: 308–312, 2004. © 2004 Wiley‐Liss, Inc.
Expression of mRNAs for DNA methyltransferases and methyl‐CpG‐binding proteins in the human female germ line, preimplantation embryos, and embryonic stem cells
Authors: Huntriss J. , Hinkins M. , Oliver B. , Harris S.E. , Beazley J.C. , Rutherford A.J. , Gosden R.G. , Lanzendorf S.E. , Picton H.M.
Published: January 2004

Recent evidence indicates that mammalian gametogenesis and preimplantation development may be adversely affected by both assisted reproductive and stem cell technologies. Thus, a better understanding of the developmental regulation of the underlying epigenetic processes that include DNA methylation is required. We have, therefore, monitored the expression, by PCR, of the mRNAs of DNA methyltransferases (DNMTs), methyl‐CpG‐binding domain proteins (MBDs), and CpG binding protein (CGBP) in a developmental series of amplified cDNA samples derived from staged human ovarian follicles, oocytes, preimplantation embryos, human embryonic stem (hES) cells and in similar murine cDNA samples. Transcripts of these genes were detected in human ovarian follicles (DNMT3A, DNMT3b1, DNMT3b4, DNMT1, MDBs1–4, MeCP2, CGBP), germinal vesicle (GV) oocytes (DNMT3A, DNMT3b1, DNMT1, MDBs1–4, MeCP2, CGBP), mature oocytes (DNMT3A, DNMT3b1, DNMT1, CGBP), and preimplantation embryos (DNMT3A, DNMT3b1, DNMT1, DNMT3L, MBD2, MDB4, CGBP). Differential expression of DNMT3B gene transcripts in undifferentiated (DNMT3b1) and in vitro differentiated human ES cells (DNMT3b3) further demonstrated an association of the DNMT3b1 transcript variant with totipotent and pluripotent human cells. Significantly, whilst the murine Dnmt3L gene is both expressed and essential for imprint establishment during murine oogenesis, transcripts of the human DNMT3L gene were only detected after fertilisation. Therefore, the mechanisms and/or the timing of imprint establishment may differ in humans. Mol. Reprod. Dev. 67: 323–336, 2004. © 2004 Wiley‐Liss, Inc.
Minimal path broadcast networks
Authors: Farley Arthur M.
Published: January 2004

Broadcasting is the communication process whereby a message that is initially known by one site becomes known to all sites of a network. Messages are transmitted by calls from senders to sets of receivers. In path broadcasting, a site can call nonneighboring sites over paths in the network. A call occupies all sites and edges on the path followed by the call; thus, any calls made concurrently must be vertex‐disjoint. We discuss the design of sparse networks that allow path broadcasting to be completed in minimum time under three different path broadcast models. © 2004 Wiley Periodicals, Inc.
An exact algorithm for the min‐cost network containment problem
Authors: Pesenti Raffaele , Rinaldi Franca , Ukovich Walter
Published: January 2004

A network design problem which arises in the distribution of a public utility provided by several competitive suppliers is studied. The problem addressed is that of determining minimum‐cost (generalized) arc capacities in order to accommodate any demand between given source–sink pairs of nodes, where demands are assumed to fall within predetermined ranges. Feasible flows are initially considered as simply bounded by the usual arc capacity constraints. Then, more general linear constraints are introduced which may limit the weighted sum of the flows on some subsets of arcs. An exact cutting plane algorithm is presented for solving both of the above cases and some computational results are reported. © 2004 Wiley Periodicals, Inc.
The absolute center of a network
Authors: Dvir Dov , Handler Gabriel Y.
Published: January 2004

This paper presents a new algorithm for finding an absolute center (minimax criterion) of an undirected network with n nodes and m arcs based on the concept of minimum‐diameter trees. Local centers and their associated radii are identified by a monotonically increasing sequence of lower bounds on the radii. Computational efficiency is addressed in terms of worst‐case complexity and practical performance. The complexity of the algorithm is 0(n2 ℓg n + mn). In practice, because of its very rapid convergence, the algorithm renders the problem amenable even to manual solution for quite large networks, provided that the minimal‐distance matrix is given. Otherwise, evaluation of this matrix is the effective computational bottleneck. An interesting feature of the algorithm and its theoretical foundations is that it synthesizes and generalizes some well‐known results in this area, particularly Halpern's lower bound on the local radius of a network and properties of centers of tree networks. © 2004 Wiley Periodicals, Inc.
D‐branes in Standard Model building, gravity and cosmology
Authors: Kiritsis E.
Published: January 2004

This is a review of aspects of D‐brane applications to particle physics and cosmology. D‐branes provide interesting alternatives to standard unification of interactions. Moreover they entail new mechanisms in cosmology that have the potential to explain recent observational data.
Open string fields and D‐branes
Authors: Rastelli L.
Published: January 2004

These lecture notes review some modern developments in open string field theory. We begin with a discussion of the physical motivations and general framework of open SFT. We then briefly introduce and contrast the two basic formalisms, Boundary SFT and cubic SFT, and summarize the main results about tachyon condensation obtained with both approaches. Next, we review the Vacuum SFT conjecture, according to which D‐brane solutions correspond to string fields that are projectors of Witten's *‐algebra. We describe the Boundary CFT technique to compute *‐products and construct projector solutions. We argue that VSFT accounts precisely for the expected moduli space of D‐branes.
On (orientifold of) type IIA on a compact Calabi‐Yau
Authors: Misra A.
Published: January 2004

We study the gauged sigma model and its mirror Landau‐Ginsburg model corresponding to type IIA on the Fermat degree‐24 hypersurface in WCP4[1,1,2,8,12] (whose blow‐up gives the smooth CY3(3,243)) away from the orbifold singularities, and its orientifold by a freely‐acting antiholomorphic involution. We derive the Picard‐Fuchs equation obeyed by the period integral as defined in [1, 2], of the parent 𝒩 = 2 type IIA theory of [3]. We obtain the Meijer's basis of solutions to the equation in the large and small complex structure limits (on the mirror Landau‐Ginsburg side) of the abovementioned Calabi‐Yau, and make some remarks about the monodromy properties associated based on [4], at the same and another MATHEMATICAlly interesting point. Based on a recently shown 𝒩 = 1 four‐dimensional triality [6] between Heterotic on the self‐mirror Calabi‐Yau CY3(11,11), M theory on ${CY_3(3,243)\times S^1\over{\bf Z}_2}$ and F‐theory on an elliptically fibered CY4 with the base given by CP1 × Enriques surface, we first give a heuristic argument that there can be no superpotential generated in the orientifold of of CY3(3,243), and then explicitly verify the same using mirror symmetry formulation of [2] for the abovementioned hypersurface away from its orbifold singularities. We then discuss briefly the sigma model and the mirror Landau‐Ginsburg model corresponding to the resolved Calabi‐Yau as well.
Aspects of stability and phenomenology in type IIA orientifolds with intersecting D6‐branes
Authors: Ott T.
Published: January 2004

Intersecting branes have been the subject of an elaborate string model building for several years. After a general introduction into string theory, this work introduces in detail the toroidal and \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$\mathbb{Z}_N$\end{document}‐orientifolds. The picture involving D9‐branes with B‐fluxes is shortly reviewed, but the main discussion employs the T‐dual picture of intersecting D6‐branes. The derivation of the R‐R and NS‐NS tadpole cancellation conditions in the conformal field theory is shown in great detail. Various aspects of the open and closed chiral and non‐chiral massless spectrum are discussed, involving spacetime anomalies and the generalized Green‐Schwarz mechanism. An introduction into possible gauge breaking mechanisms is given, too. Afterwards, both 𝒩 = 1 supersymmetric and non‐supersymmetric approaches to low energy model building are treated. Firstly, the problem of complex structure instabilities in toroidal ΩR‐orientifolds is approached by a \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$\mathbb{Z}_3$\end{document}‐orbifolded model. In particular, a stable non‐supersymmetric standard‐like model with three fermion generations is discussed. This model features the standard model gauge groups at the same time as having a massless hypercharge, but possessing an additional global B‐L symmetry. The electroweak Higgs mechanism and the Yukawa couplings are not realized in the usual way. It is shown that this model descends naturally from a flipped SU(5) GUT model, where the string scale has to be at least of the order of the GUT scale. Secondly, supersymmetric models on the \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$\mathbb{Z}_4$\end{document}‐orbifold are discussed, involving exceptional 3‐cycles and the explicit construction of fractional D‐branes. A three generation Pati‐Salam model is constructed as a particular example, where several brane recombination mechanisms are used, yielding non‐flat and non‐factorizable branes. This model even can be broken down to a MSSM‐like model with a massless hypercharge. Finally, the possibility that unstable closed and open string moduli could have played the role of the inflaton in the evolution of the universe is being explored. In the closed string sector, the important slow‐rolling requirement can only be fulfilled for very specific cases, where some moduli are frozen and a special choice of coordinates is taken. In the open string sector, inflation does not seem to be possible at all.
The demographic transition revisited as a global process
Authors: Reher David S.
Published: January 2004

With dramatic declines in fertility taking place throughout the world, it is increasingly important to understand the demographic transition as a global process. While this universality was a cornerstone of classic transition theories, for many decades it was largely neglected by experts because fertility in the developing world did not seem to follow the expected pattern. When comparing earlier and more recent transition experiences, important similarities and disparities can be seen. Everywhere mortality decline appears to have played a central role for fertility decline. The differences in the timing of the response of fertility to mortality decline, with very small gaps historically and prolonged ones in more recent transitions, plus the much more rapid decline in vital rates in many developing countries, constitute an important challenge to any general explanation of the process. The specific characteristics of recent transitions have led to decades of higher population growth rates, and promise to give way to much more rapid dynamics of population ageing in many countries. This may limit the ability of newcomers to take full advantage of the demographic transition for the social and economic modernisation of their societies. Copyright © 2004 John Wiley & Sons, Ltd.
Spaces of silence: single parenthood and the ‘normal family’ in Singapore
Authors: Wong Theresa , Yeoh Brenda S. A. , Graham Elspeth F. , Teo Peggy
Published: January 2004

Alternative family forms have begun to emerge in the Confucian societies of East and Southeast Asia, concomitant with widespread demographic changes and new socioeconomic conditions. In Singapore, the state tends to configure ‘single parents’ – including divorcees, unmarried parents and widowed parents – as ‘unfortunate’ and constituting an unhealthy trend, in opposition to the normal, dual‐parent household. This paper examines how single parents in Singapore reconfigure their definitions of the family both discursively and through practical means, in response to the ‘traditional’, Confucian concept of the complete family propounded by the government. Through in‐depth interviews with middle‐class Chinese Singaporean single mothers and fathers, this paper also explores how single parents employ strategies at two levels: in practical decisions relating to childcare; and discursively, through the articulation of remarriage and fertility desires, in which patriarchal notions of the roles of husband/wife and mother/father are embedded. Copyright © 2004 John Wiley & Sons, Ltd.
Forced or free movers? The motives, voluntariness and selectivity of interregional migration in the Nordic countries
Authors: Lundholm Emma , Garvill Jörgen , Malmberg Gunnar , Westin Kerstin
Published: January 2004

This paper examines interregional migration within the five Nordic countries, Sweden, Norway, Denmark, Finland and Iceland, focusing on the impacts on migration decisions. A background to the study is the regional demographic polarisation of the five countries and the debate about labour market migration. The main questions of the study are: (a) What motives, apart from those relating to the labour market, are important to interregional migrants? (b) Do migrants perceive their decision to move as voluntary? (c) Are migration decisions in conflict with peoples' life projects, values and attitudes? The empirical analysis is based on 9600 responses to a survey conducted in all five countries, with participants including both those who have changed resident municipality in the last two years (migrants) and those who have lived in the same municipality for more than five years (stayers). The study reveals that only about one in five migrants give employment as a major motive for moving. Environmental and social factors are often more important. The majority of migrants claim that their decision to move is voluntary. The results also confirm previous research suggesting that migrants are more likely to be young, single people and have a higher educational level than stayers. There is also evidence that migration is often compatible with migrants' values and preferences. Copyright © 2004 John Wiley & Sons, Ltd.
Brief report: Test–retest reliability of self‐reported adolescent risk behaviour
Authors: Flisher Alan J , Evans Janet , Muller Martie , Lombard Carl
Published: January 2004

There is a paucity of test–retest reliability data for adolescent self‐reports of a wide range of risk behaviours. Grade 8 and 11 Students (N=358) completed a questionnaire on two occasions between 10 and 14 days apart. It included items about use of various substances, violent behaviour, suicidality, and sexuality. Cohen's kappa was almost perfect for 1 item (κ=85.4%); in the substantial range (61–80%) for 4 items; and in the moderate range (41–60%) for 3 items. For the remaining 7 items, the percentage agreement was higher than 92.0%. The questionnaire thus demonstrates adequate test–retest reliability.
TRP channels as potential drug targets
Authors: Wissenbach Ulrich , Niemeyer Barbara A. , Flockerzi Veit
Published: January 2004

Abstract Calcium (Ca2+) is an ubiquitous intracellular signal that is responsible for a plethora of cellular processes including fertilization, secretion, contraction, neuronal signaling and learning. In addition, changes in intracellular Ca2+ have been known to influence cell proliferation and differentiation for more than three decades. Recent studies have indicated that members of the transient receptor potential (TRP) family of ion channels which respond to many different modes of stimulation both from within and outside the cell may be a primary mode of cation and Ca2+ entry into cells and may have roles in growth control. Moreover, changes in the expression of these channels may contribute to certain cancers. In the following, recent results concerning the expression and function of members of this family of ion channels are summarized.
Subcellular localization of MAK‐V/Hunk protein kinase expressed in COS‐1 cells
Authors: Korobko Elena V. , Kiselev Sergey L. , Korobko Igor V.
Published: January 2004

MAK‐V/Hunk is a MARK/Par‐1‐related protein kinase, whose function is unknown. We studied the subcellular localization of MAK‐V/Hunk in COS‐1 cells by immunofluorescence. It has a nucleocytoplasmic distribution and is localized to the centrosome, as indicated by co‐localization with γ‐tubulin. A putative kinase‐deficient mutant, with a mutation in the invariant lysine residue in the catalytic domain, was not targeted to the nucleus or centrosome. These results suggest that the nuclear and centrosomal targeting of MAK‐V/Hunk is specific, and is likely to be coupled to its catalytic activity.
Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy?
Authors: Gorwood P.
Published: January 2004

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are the most common type of anxiety-mood comorbidity. Up to 80% of subjects with lifetime GAD also have a comorbid mood disorder during their lifetime. Many hypotheses have been raised to explain such high comorbidity. Pleiotropy, i.e. a single genetic mutation explains (apparently) different disorders, is one of them and is hereby reviewed. Importance and reliability of GAD and MDD comorbidity (1); Evidence in favour of co-aggregation of GAD and MDD within families (the risk of one disorder in a proband increasing the risk for the other in relatives) (2); substantial heredity for both disorders according to twin studies with evidence for genetic correlation of unity between the two disorders (3); existence of numerous mechanisms (4) potentially linking the two disorders to common vulnerability genes, are all in accordance with such a hypothesis. Some examples of potentially shared mechanisms (such as CRF dysregulation or abnormal transcription factors) and possible common vulnerability genes (for example, the serotonin transporter gene) are given to highlight the pleiotropy hypothesis.
Safety Review of Benzalkonium Chloride Used as a Preservative in Intranasal Solutions: An Overview of Conflicting Data and Opinions
Authors: Marple Bradley , Roland Peter , Benninger Michael
Published: January 2004

BACKGROUND

For most multiuse aqueous nasal, ophthalmic, and otic products, benzalkonium chloride (BKC) is the preservative of choice. The American College of Toxicology has concluded that BKC can be safely used as an antimicrobial agent at concentrations up to 0.1%. BKC has been in clinical use since 1935 and is contained in a wide variety of prescription and over‐the‐counter products. However, over the past several years there have been conflicting reports of damage to human nasal epithelia and/or exacerbation of rhinitis medicamentosa associated with intranasal products containing BKC.

OBJECTIVE

We sought to review the published literature and determine whether there is sufficient, clinically significant data that would confirm that intranasal products containing BKC are likely to damage human nasal epithelia or exacerbate rhinitis medicamentosa.

METHODS

A literature search was conducted for in vivo and in vitro studies that evaluated the effects of BKC on human nasal epithelia.

RESULTS

A total of 18 studies (14 in vivo, 4 in vitro) were identified that evaluated short‐ and long‐term exposure of concentrations of BKC in concentrations ranging from 0.00045% to 0.1%. Eight studies, including a 6‐month and 1‐year long‐term treatment study, demonstrated no toxic effects associated with BKC, indicating that BKC was neither harmful to nasal tissue nor prone to exacerbate rhinitis medicamentosa. Furthermore, of the 10 studies that concluded that BKC resulted in degenerative changes in human nasal epithelia (eg, ciliary beat frequency, ciliary morphology, mucociliary clearance, epithelial thinning and/or destruction) or that BKC exacerbates rhinitis medicamentosa, only 2 (it was 2 according to the Results section) of these studies were supported by statistically significant differences between BKC and placebo or active control groups were compared. It is important to note that in both of these studies, the protocol incorporated the use or oxymetazoline in some or all of the subjects. Oxymetazoline is associated with rhinitis medicamentosa.

CONCLUSION

Intranasal products containing the preservative BKC appear to be safe and well tolerated for both long‐ and short‐term clinical use.
Injection Snoreplasty: Investigation of Alternative Sclerotherapy Agents
Authors: Brietzke Scott E. , Mair Eric A.
Published: January 2004

OBJECTIVE

Palatal sclerotherapy with sodium tetradecyl sulfate (“injection snoreplasty”) was recently introduced as a safe and effective treatment for primary snoring. However, multiple other sclero‐therapy agents also have excellent safety records and documented efficacy in the head and neck. Widely available and inexpensive agents were evaluated as potential palatal sclerosing agents for the treatment of snoring.

STUDY DESIGN AND SETTING

A described canine palatal flutter model was used to evaluate the palatal stiffening efficacy of ethanol, doxycycline, and hypertonic saline in comparison to 3% sodium tetradecyl sulfate (STS) and a negative control (normal saline). Based on the animal study results, a human pilot study with ethanol was performed with subjective and objective data.

RESULTS

Ethanol was found to be equally effective as 3% STS in the canine model. Doxycycline was effective but less so, and hypertonic saline was comparatively ineffective. Palatal injection in human patients with 50% ethanol was found to produce equivalent subjective and objective snoring efficacy and equivalent pain and recovery time compared with 3% STS. However, there was a higher rate of transient palatal fistula with ethanol. CONCLUSIONS AND SIGNIFICANCE: Injection snoreplasty with 50% ethanol is equally efficacious compared with 3% STS. There could be a higher fistula rate with the use of ethanol, although this complication has been self‐limited and transient in every case.
Acoustic Pharyngometry Patterns of Snoring and Obstructive Sleep Apnea Patients
Authors: Kamal Ibrahim
Published: January 2004

OBJECTIVE

Anatomic narrowing of the pharyngeal airway increases the relative negative pressure generated during inspiration, thus affecting the dynamic behavior of the upper airway. The aim of this work was to measure pharyngeal area in snoring patients with and without obstructive sleep apnea (OSA), as categorized by polysomnography and by acoustic pharyngometry, and to analyze the different curve patterns obtained from patients of both groups.

METHODS

We examined 50 snorers who were divided into 2 groups matched for age, gender, and body mass index.

RESULTS

Mean Apnea Index (AI) in nonapneic snorers (group 1) was 4, and mean pharyngeal area was 2.41 cm2. In snoring patients with OSA (group 2), mean AI was 25.9 with a mean pharyngeal area of 1.589 cm2(P< 0.001). In both groups, the dependent variable (AI) can be predicted from a linear relation with the independent variable (pharyngeal area) with normality and constant variance tests passed. In group 1, the resulting curve can be 1 of 2 types depending on the relative area of the pharyngeal segment to the velopharyngeal area. In group 2, the curve pattern can be categorized into 3 patterns depending on the possible pathology of pharyngeal obstruction.

CONCLUSION

The acoustic reflection technique is reproducible, noninvasive, and free from potential side effects. The good correlation between AI and pharyngeal area adds to the potential of acoustic pharyngometry. Careful study of the pharyngeal cross‐sectional area and curve topography may give a good idea about the site of upper airway obstruction.
Nasopharyngeal Granulomatous Inflammation and Tuberculosis Complicating Undifferentiated Carcinoma
Authors: Chan Amy B. W. , Ma Tony K. F. , Yu Brian K. H. , King Ann D. , Ho Fiona N. Y. , Tse Gary M. K.
Published: January 2004

OBJECTIVE

Four cases of nasopharyngeal granulomatous inflammation after radiotherapy for undifferentiated carcinoma were analyzed for tuberculosis, and the histologic features were compared. STUDY DESIGN AND SETTING: We conducted a retrospective study with analysis of tuberculosis by Ziehl Neelsen staining and polymerase chain reaction analysis for Mycobacterium tuberculosis DNA on histologic materials.

Results

Three patients had previous nasopharyngeal undifferentiated carcinoma, one had previous metastatic undifferentiated carcinoma to cervical lymph nodes, and all patients received similar radiotherapy regimen. The light microscopic features were similar with epithelioid histiocytes and granulomas with Langhan's giant cells. In 3 cases, acid‐fast bacilli were identified by Ziehl Neelsen stain, and 1 was negative. The results of 2 cases were confirmed by polymerase chain reaction analysis for Myocbacterium tuberculosis DNA.

CONCLUSION

Granulomatous reaction after radiotherapy of nasopharyngeal undifferentiated carcinoma can be caused by tuberculosis.

SIGNIFICANCE

Diligent search for organisms in postirradiation granulomatous inflammation is warranted to avoid missing an occult tuberculosis infection.
Total Ossiculoplasty with Footplate Removal
Authors: Berenholz Leonard , Lippy William H.
Published: January 2004

OBJECTIVE

We reviewed the results and management of cases in which total ossiculoplasty requires footplate removal.

STUDY DESIGN AND SETTING

We conducted a retrospective review of 10 patients who underwent total ossiculoplasty with footplate removal between 1999 and 2002. These 10 patients represented 5.4% of those undergoing stapedectomy (n = 91) and ossiculoplasty (n = 93) during these years at a tertiary otologic referral center.

RESULTS

A total of 10 patients were evaluated, with a mean 17‐month follow‐up. Closure of air‐bone gap (ABG) to within 20 dB was achieved in 6 of 10 patients (60%). Mean postoperative ABG was 21.7 dB (500 to 4000 Hz) with an average 4‐frequency pure tone improvement of 20.7 dB. Operative findings included extensive tympanosclerosis, partial obstruction of oval window by facial nerve, and changes from prior surgery. There were no patients with postoperative sensorineural hearing loss.

CONCLUSIONS

The need to open the footplate in cases of total ossiculoplasty is uncommon. This may be accomplished with good improvement in hearing with minimal risk.
Radiofrequency Soft Palate Procedure in Snoring: Influence of Energy Delivered
Authors: Kania Romain E. , Schmitt Emmanuel , Petelle Boris , Meyer Bernard
Published: January 2004

OBJECTIVE

We conducted a retrospective study to evaluate the influence of amount of energy delivered during radiofrequency procedure for soft palate reduction in snoring, to improve the cure rate.

METHODS

Consecutive patients with chronic disruptive snoring presenting to our department were successively treated in an outpatient procedure. A visual analog scale was used to assess the severity of snoring by the bed partner and the pain by the patient, before treatment and after each treatment session. The soft palate was divided into 3 treatment sites: middle, lateral right, and lateral left. Any mucosal injury of the soft palate was classified as a complication.

RESULTS

Forty‐3 patients were classified into 2 groups according to energy assignment. The total amount of energy delivered was 1250 J in group 1 (n = 15) and 1500 J in group 2 (n = 28). Energy was predominantly distributed in the middle of the soft palate in group 1 (550 J) and group 2 (800 J). After each treatment session, the 1500‐J delivery of radiofrequency energy (total per session) led to a better snoring grading reduction in comparison with the 1250‐J delivery with a significant difference after 2 treatment sessions (P < 0.05). The mean pain score and the incidence rate of complications per treatment were not statistically different in comparing both groups.

CONCLUSION

Better snoring scores can be expected by increasing radiofrequency energy applied to the soft palate. Further randomized long‐term investigations are required to confirm that the cure rate can be improved when increasing energy with a suitable distribution and good clinical tolerance.
Localization and Level of Expression of β‐Catenin in Human Laryngeal Squamous Cell Carcinoma
Authors: Lopez‐Gonzalez Jose Sullivan , Cristerna‐Sanchez Lissete , Vazquez‐Manriquez Maria Eugenia , Jimenez‐Orci Gonzalo , Aguilar‐Cazares Dolores
Published: January 2004

OBJECTIVE

We studied the participation of β‐catenin in the histologic differentiation of laryngeal squamous cell carcinomas.

STUDY DESIGN AND SETTING

At the National Institute of Respiratory Diseases, a tertiary referral center, localization and level of expression of β‐catenin were compared between normal epithelium (15 cases) and primary tumors in different degrees of differentiation (38 cases), using an immunohistochemical procedure.

RESULTS

Cell membrane staining of β‐catenin was observed in normal epithelium and in well and moderately differentiated carcinomas. Cytoplasmic redistribution was observed in poorly differentiated carcinomas. Loss of β‐catenin correlated with tumor dedifferentiation.

CONCLUSION

Reduction of cell membrane β‐catenin expression correlated with tumor dedifferentiation.

SIGNIFICANCE

Loss of β‐catenin may lead to diminishing the strength of the intercellular adhesion system, thereby promoting the invasive phenotype of the squamous cell carcinoma of the larynx.
The Role of the Genial Bone Advancement Trephine System in Conjunction with Uvulopalatopharyngoplasty in the Multilevel Management of Obstructive Sleep Apnea
Authors: Miller Frank R. , Watson Daniel , Boseley Mark
Published: January 2004

OBJECTIVES

The successful surgical management of obstructive sleep apnea (OSA) requires surgical procedures that address both retropalatal and retrolingual airway obstruction. The Genial Bone Advancement Trephine (GBAT) system is a new, 1‐step system that allows for isolation and advancement of the genioglossus muscle via a guided trephine system. The purpose of this project was to describe our experience using the GBAT system to perform genioglossus advancement (GGA) in conjunction with uvulopalatopharyngoplasty (UPPP) in the surgical management of OSA.

STUDY DESIGN: Retrospective analysis of 35 consecutive patients undergoing GGA using the GBAT system in conjunction with UPPP for the management of OSA during a 3‐year period (1999 to 2002).

RESULTS: Twenty‐four patients had complete preoperative and postoperative polysomnographic data. A 70% reduction in the Respiratory Disturbance Index (RDI) and Apnea Index (AI) in the preoperative versus postoperative PSG (RDI, 52.9 ± 17.1 versus 15.9 ± 7.5; AI, 20.1 ± 6.7 versus 6.1 ± 4.5; P ≤ 0.0001). The lowest oxygen desaturation increased from 80% to 88% (P = 0.0002), and the posterior airway increased from 7.9 to 12.6 mm (P < 0.0001). With a surgical cure defined as a greater than 50% reduction in the RDI and a final postoperative RDI of less than 20 events per hour, the true surgical cure rate was 67% (16 of 24 patients).

CONCLUSIONS: The GBAT system performed in conjunction with UPPP can produce significant reductions in RDI and AI while improving the oxygen desaturation and enlarging the posterior airway space. The effective cure rates using the GBAT system are in agreement with previous reports in the literature using various GGA techniques. The GBAT may have some advantages in terms of simplicity and safety.
The Risk of Aspiration of Pureed Food as Determined by Flexible Endoscopic Evaluation of Swallowing with Sensory Testing
Authors: Perlman Philip W. , Cohen Manderly A. , Setzen Michael , Belafsky Peter C. , Guss Joel , Mattucci Kenneth F. , Ditkoff Michael
Published: January 2004

OBJECTIVE

This study evaluates the risk of aspiration of pureed foods in patients with dysphagia with increasing sensory deficits of the hypopharynx with intact versus impaired pharyngeal muscular tone (pharyngeal squeeze).

STUDY DESIGN

Two hundred four dysphagic patients underwent flexible endoscopic evaluation of swallowing with sensory testing and were prospectively divided into 3 groups, with normal, moderate, and severe sensory deficits. Each group was divided into those with normal and those with impaired pharyngeal squeeze. Subjects were given pureed food boluses and were evaluated for aspiration.

RESULTS

There was a significant difference in the incidence of aspiration of pureed foods for normal and moderate sensory loss when comparing normal and impaired pharyngeal squeeze (P < 0.001, Fisher exact test). There was no significant difference in the severe sensory loss group. In both the normal and impaired pharyngeal squeeze groups, there was no significant difference in aspiration as the sensory deficit increases.

CONCLUSIONS

Patients with impaired pharyngeal squeeze at different levels of sensory deficits are at significantly greater risk for aspiration of pureed foods compared with those with normal squeeze. However, as sensory deficits increased, the patients did not show a significant increase in aspiration. The aspiration of pureed foods may depend more on muscle tone of the hypopharynx than on sensation. Dysphagic patients who are given a pureed diet to prevent aspiration may still be at risk for aspiration. This may be easily predicted by the use of flexible endoscopic evaluation of swallowing with sensory testing in conjunction with evaluation of pharyngeal muscle tone. (Otolaryngol Head Neck Surg 2004;130:80‐3.)
Techniques of Intranasal Steroid Use
Authors: Benninger Michael S. , Hadley James A. , Osguthorpe J. David , Marple Bradley F. , Leopold Donald A. , Derebery M. Jennifer , Hannley Maureen
Published: January 2004

OBJECTIVE

The effectiveness of topical intranasal steroids (INS) sprays for the treatment of allergic and nonallergic rhinitis may be limited by lack of instruction in the optimal spray technique. To determine whether the technique used affects the efficacy and safety of the product, this review of evidence had the goal of identifying and establishing a preferred method of applying INS sprays.

STUDY DESIGN

A MEDLINE search of pertinent literature on 7 INS and 1 intranasal antihistamine spray preparations conducted with the use of appropriate search terms, yielded an initial 121 articles, 29 of which were identified as appropriate for review and grading for quality of evidence.

RESULTS

The analysis provided no definitive evidence regarding how best to instruct patients to use INS or antihistamine spray devices.

CONCLUSIONS

On the basis of a lack of clear evidence regarding instructions to maximize efficacy and safety of these drugs, the panel recommended a 7‐step standard technique. (Otolaryngol Head Neck Surg 2004;130:5–24.)
Interaction of checkpoint kinase 1 and the X‐linked inhibitor of apoptosis during mitosis
Authors: Galvan V , Kurakin A.V , Bredesen D.E
Published: January 2004

We report here that the checkpoint kinase Chk1 and the inhibitor of apoptosis protein (IAP) family member XIAP can be found in a complex in association with condensed chromosomes aligned at the metaphase plate during mitosis. The interaction between Chk1 and XIAP was transient and followed the breakdown of the nuclear envelope. Chk1 and XIAP also formed a complex in vitro and in coimmunoprecipitation experiments. The interaction between Chk1 and the BIR3 domain of XIAP in vitro required an N‐terminal sequence in Chk1 that is identical to the BIR‐binding motif at the N‐terminus of HID. An interaction of Chk1 and XIAP may imply a mechanism of coupling between the regulatory networks that control cell cycle progression and apoptosis during mitosis.
Conjugate for efficient delivery of short interfering RNA (siRNA) into mammalian cells
Authors: Muratovska Aleksandra , Eccles Michael R
Published: January 2004

The efficient delivery of short interfering RNAs (siRNAs) into cells provides a powerful approach to study cellular functions. SiRNAs were coupled to the membrane permeant peptides (MPPs) penetratin and transportan to improve their uptake by cells. Thiol‐containing siRNAs corresponding to luciferase, or green fluorescent protein (GFP) transgenes, were synthesized and conjugated to penetratin or transportan via a disulfide bond that is labile in the reducing environment of the cytoplasm. These MPP‐siRNAs efficiently reduced transient and stable expression of reporter transgenes in several mammalian cell types in a high proportion of cells, and demonstrated equivalent or better delivery characteristics than cationic liposomes with fewer manipulations.