bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of maf family proteins in lens development
Authors: Reza Hasan Mahmud , Yasuda Kunio
Published: February 2004

Lens provides a good model for studying developmental cues relevant to cellular and molecular interactions. Basic region/leucine zipper (bZIP) transcription factors have been found to play key roles during eye formation in various species, including human, mouse, rat, Xenopus, zebrafish, chick, and quail. Different ocular developmental anomalies associated with MAF mutation in human implicate its active role during eye development. Several members of the maf gene family with this bZIP motif participate directly in lens morphogenesis. One vital Maf protein, L‐Maf, is expressed in developing lens cells of chick embryos. Its homolog recently has been detected in lens placode of Xenopus embryos and regulates expression of lens fiber‐specific genes in this species. Ectopic expression of L‐Maf can induce lens‐specific genes in cultured retina cells and embryonic ectoderm. The dominant‐negative form of L‐Maf causes the suppression of crystallin expression and subsequently inhibits lens formation, indicating that L‐Maf plays a central role in chick lens development. Developmental Dynamics 229:440–448, © 2004 Wiley‐Liss, Inc.
Angiopoietin 1 expression levels in the myocardium direct coronary vessel development
Authors: Ward Nicole L. , Van Slyke Paul , Sturk Celina , Cruz Maribelle , Dumont Daniel J.
Published: February 2004

Mutational studies in genetically engineered mice have shown that the angiopoietin/Tie2(Tek) signaling pathway is indispensable for vascular development. To further investigate the role of Angiopoietin 1 in heart development, we developed transgenic mice that express Angiopoietin 1 under control of doxycycline in cardiac myocytes. Ninety percent of all transgenic mice die between embryonic day 12.5 and 15.5. Beginning at embryonic day 12.5, transgenic mice exhibit dilated atria, a significant thinning of the myocardial wall, and eventual outflow tract collapse. In addition, hearts of the most severely affected transgenic embryos have no coronary arteries as a result of the defective development and maintenance of the epicardium. The subsequent lack of blood and nutrient delivery to the developing heart may account for decreases in N‐cadherin expression and subsequent loss of cell–cell contact leading to cell death, and ultimately the collapse and hemorrhage of the heart. These results suggest a pivotal role for Angiopoietin 1 in cardiovascular development, specifically the development of the epicardium and coronary vasculature. Developmental Dynamics 229:500–509, 2004. © 2004 Wiley‐Liss, Inc.
Signals regulating tendon formation during chick embryonic development
Authors: Edom‐Vovard Frédérique , Duprez Delphine
Published: February 2004

Tendons are collagen‐rich structures that link muscle to cartilage. By using quail–chick chimeras, it has been shown that tendon and cartilage cells originate from the same mesodermic compartment, which is distinct from that giving rise to muscle cells. Axial tendons originate from the sclerotomal compartment, and limb tendons originate from the lateral plate, whereas axial and limb muscles derive from dermomyotomes. Despite these different embryologic origins, muscle and tendon morphogenesis occurs in close spatial and temporal association. Facilitated by the distinct embryologic origin of myogenic and tendon cells, surgical studies in the avian embryo have highlighted interactions between tendons and muscles, during embryonic development. However, these interactions seem to differ between axial and limb levels. The molecular mechanisms underlying muscle and tendon interactions have been shown recently to involve different members of the fibroblast growth factor family. This review covers the available data on the early steps of tendon formation in the limb and along the primary axis. The relationship with muscle morphogenesis will be highlighted. Developmental Dynamics 229:449–457, 2004. © 2004 Wiley‐Liss, Inc.
Somatic transgenesis using retroviral vectors in the chicken embryo
Authors: Ishii Yasuo , Reese David E. , Mikawa Takashi
Published: February 2004

The avian embryo is an excellent model system for experimental studies because of its accessibility and ease of microsurgical manipulations. While the complete chicken genome sequence will soon be determined, a comprehensive germ cell transmission‐based genetic approach is not available for this animal model. Several techniques of somatic cell transgenesis have been developed in the lpast decade. Of these, the retroviral shuttle vector system provides both (1) stable integration of exogenous genes into the host cell genome, and (2) constant expression levels in a target cell population over the course of development. This review summarizes retroviral vectors available for the avian model and outlines the uses of retroviral‐mediated gene transfer for cell lineage analysis as well as functional studies of genes and proteins in the chick embryo. Developmental Dynamics 229:630–642, 2004. © 2004 Wiley‐Liss, Inc.
Bves expression during avian embryogenesis
Authors: Osler Megan E. , Bader David M.
Published: February 2004

Bves (blood vessel/epicardial substance) is a transmembrane protein postulated to play a role in cell adhesion. While it is clear that Bves and gene products of the same family are expressed in adult striated muscle cells, the distribution of these proteins during development has not been critically examined. An understanding of the expression pattern of Bves is essential for a determination of protein function and its role in embryogenesis. In this study, we present an expression analysis of Bves during chick gastrulation and germ layer formation. Our data show that Bves is expressed in epithelia of all three germ layers early in development. Furthermore, Bves protein is observed in epithelial tissues during organogenesis, specifically the developing epidermis, the gut endoderm, and the epicardium of the heart. These data support the hypothesis that Bves may play a role in cell adhesion and movement of epithelia during early embryogenesis. Developmental Dynamics 229:658–667, 2004. © 2004 Wiley‐Liss, Inc.
Expression analysis of chick Wnt and frizzled genes and selected inhibitors in early chick patterning
Authors: Chapman Susan C. , Brown Ryan , Lees Lydia , Schoenwolf Gary C. , Lumsden Andrew
Published: February 2004

Wnt signaling is an important component in patterning the early embryo and specifically the neural plate. Studies in Xenopus, mouse, and zebrafish have shown that signaling by members of the Wnt family of secreted signaling factors, their Frizzled receptors and several inhibitors (sFRP1, sFRP2, sFRP3/Frzb1, Crescent/Frzb2, Dkk1, and Cerberus) are involved. However, very little is known about the expression of genes in the Wnt signaling pathway during early anterior neural patterning in chick. We have performed an expression analysis at neural plate stages of several Wnts, Frizzled genes, and Wnt signaling pathway inhibitors using in situ hybridization. The gene expression patterns of these markers are extremely dynamic. We have identified two candidate molecules for anterior patterning of the neural plate, Wnt1 and Wnt8b, which are expressed in the rostral ectoderm at these stages. Further functional studies on the roles of these markers are underway. Developmental Dynamics 229:668–676, 2004. © 2004 Wiley‐Liss, Inc.
Immunoglobulin gene conversion: Insights from bursal B cells and the DT40 cell line
Authors: Arakawa Hiroshi , Buerstedde Jean‐Marie
Published: February 2004

Chicken B cells diversify their immunoglobulin (Ig) light and heavy chain genes by pseudogene templated gene conversion within the bursa of Fabricius. Although Ig gene conversion was initially believed to occur only in birds, it is now clear that most farm animals also use this elegant mechanism to develop an immunoglobulin gene repertoire. The best model to study Ig gene conversion remains the chicken Ig light chain locus due to its compact size and the fact that all the pseudogene donors are sequenced. Furthermore, gene conversion continues in the bursa‐derived DT40 cell line whose genome can be easily modified by targeted integration of transfected constructs. Disruption of the AID gene, which had been shown to control somatic hypermutation and switch recombination in mammals leads to a complete block of gene conversion in DT40 indicating that all B‐cell specific repertoire formation is controlled by the same gene. Here, we review the genetics and the molecular mechanism of Ig gene conversion based on sequence analysis of bursal B cells and gene disruption studies in the DT40 cell line. Developmental Dynamics 229:458–464, 2004. © 2004 Wiley‐Liss, Inc.
Sonic hedgehog patterning in chick neural plate is antagonized by a Wnt3‐like signal
Authors: Robertson Christie P. , Braun Michelle M. , Roelink Henk
Published: February 2004

Sonic hedgehog (Shh) patterns the dorsal‐ventral axis of the neural tube by promoting the differentiation of ventral neural cell types while suppressing dorsal neural fates. Other signals impinge upon the Shh response, biasing the differentiation of a cell. Three dorsally expressed transforming Wnts, of which the most broadly expressed is Wnt3, may be among the signals that influence the Shh response. We demonstrate that activation of Wnt signaling results in an inhibition of the Shh response in neural tissue. Additionally, we show that the expression pattern of chick Wnt3 is consistent with a role in neural patterning. These results indicate that differentiating neural tube cells, besides integrating signals from Hedgehogs and BMPs, may also incorporate a Wnt response to make cell fate decisions. Developmental Dynamics 229:510–519, 2004. © 2004 Wiley‐Liss, Inc.
Isolation of the chicken Lmbr1 coding sequence and characterization of its role during chick limb development
Authors: Maas Sarah A. , Fallon John F.
Published: February 2004

In the developing amniote limb, anteroposterior (A/P) patterning is controlled through secretion of the Sonic Hedgehog (SHH) protein by cells in the zone of polarizing activity (ZPA) located in the posterior mesoderm. In the chicken mutant oligozeugodactyly (ozd), Shh is expressed normally in the entire embryo with the exception that it is undetectable in the developing limbs; this results in the loss of specific bones in wings and legs. The ozd phenotype is similar to that of humans affected with acheiropodia (ACHR), and the ACHR mutation has been mapped to a deletion of exon 4 and portions of introns 3 and 4 in the LMBR1 gene. We have cloned the chick ortholog of LMBR1, Lmbr1, and report that, in chick, Lmbr1 is expressed within the ZPA. Although the ozd phenotype is similar to ACHR, the open reading frame of Lmbr1 is normal in ozd. Sequence analysis of Lmbr1 intron 3 demonstrated that this particular genomic region segregates with the ozd phenotype. In addition, overexpression of Lmbr1 throughout the developing limb mesoderm resulted in morphologically normal limbs. Collectively, these data suggest that the Lmbr1 coding sequence is not required for normal chick limb development. We propose that the ozd mutation is linked to the genomic region containing Shh and Lmbr1. Developmental Dynamics 229:520–528, 2004. © 2004 Wiley‐Liss, Inc.
GEISHA, a whole‐mount in situ hybridization gene expression screen in chicken embryos
Authors: Bell George W. , Yatskievych Tatiana A. , Antin Parker B.
Published: February 2004

Despite the increasing quality and quantity of genomic sequence that is available to researchers, predicting gene function from sequence information remains a challenge. One method for obtaining rapid insight into potential functional roles of novel genes is through gene expression mapping. We have performed a high throughput whole‐mount in situ hybridization (ISH) screen with chick embryos to identify novel, differentially expressed genes. Approximately 1,200 5′ expressed sequence tags (ESTs) were generated from cDNA clones of a Hamburger and Hamilton (HH) stage 4–7 (late gastrula) chick embryo endoderm–mesoderm library. After screening to remove ubiquitously expressed cDNAs and internal clustering and after comparison to GenBank sequences, remaining cDNAs (representing both characterized and uncharacterized genes) were screened for expression in HH stage 3–14 embryos by automated high throughput ISH. Of 786 cDNAs for which ISH was successfully performed, approximately 30% showed ubiquitous expression, 40% were negative, and approximately 30% showed a restricted expression pattern. cDNAs were identified that showed restricted expression in every embryonic region, including the primitive streak, somites, developing cardiovascular system and neural tube/neural crest. A relational database was developed to hold all EST sequences, ISH images, and corresponding BLAST report information, and to enable browsing and querying of data. A user interface is freely accessible at http://geisha.biosci.arizona.edu. Results show that high throughput whole‐mount ISH provides an effective approach for identifying novel genes that are differentially expressed in the developing chicken embryo. Developmental Dynamics 229:677–687, 2004. © 2004 Wiley‐Liss, Inc.
Identification of ciliary epithelial‐specific genes using subtractive libraries and cDNA arrays in the avian eye
Authors: Kubota Ryo , McGuire Chris , Dierks Blair , Reh Thomas A.
Published: February 2004

The ciliary epithelium of the ciliary body is derived from the anterior rim of the developing optic cup. Several recent studies have found that developmental abnormalities in this tissue can underlie congenital glaucoma. However, there is little known about the development of the ciliary epithelium. To better understand the developmental events responsible for the specification of this domain of the optic cup, we used a subtractive library, differential screening approach along with the construction of cDNA arrays to identify genes expressed in the ciliary epithelium of the chicken. We identified many genes specifically expressed in the ciliary epithelium, including a number that had been described previously as enriched in the ciliary epithelium of other species. By analyzing the expression of these genes during eye development, we were able to correlate the onset of ciliary epithelial gene expression with a reduction in mitotic activity in this region. We propose that the mechanisms that regulate the expression of ciliary epithelial genes are linked to the reduction in proliferation that results in the epithelial monolayer in this region. Developmental Dynamics 229:529–540, 2004. © 2004 Wiley‐Liss, Inc.
FISHing for chick genes: Triple‐label whole‐mount fluorescence in situ hybridization detects simultaneous and overlapping gene expression in avian embryos
Authors: Denkers Nathaniel , García‐Villalba Pilar , Rodesch Christopher K. , Nielson Kandice R. , Mauch Teri Jo
Published: February 2004

Multi‐color whole‐mount in situ hybridization is a powerful technique for comparing the spatial expression patterns of two or more genes in developing embryos. We have developed an amplified triple‐label whole‐mount fluorescence in situ hybridization (FISH) protocol that permits detection of three different mRNAs in a single embryo. Our protocol uses simultaneous in situ hybridization to haptenylated riboprobes, followed by sequential antibody detection using anti‐hapten antibodies conjugated to horseradish peroxidase, and the tyramide signal amplification (TSA) fluorescence detection system. Conventional fluorescence microscopy identifies areas of overlapping gene expression at the tissue level, whereas confocal fluorescence microscopy permits single‐cell resolution and differentiates specialized cell types within a given tissue. This protocol will provide researchers engaged in the use of FISH with a solid starting point for adapting their own in situ hybridization protocols, either alone or in combination with immunohistochemistry or green fluorescence protein colocalization. Developmental Dynamics 229:651–657, 2004. © 2004 Wiley‐Liss, Inc.
Dorsal versus ventral scales and the dorsoventral patterning of chick foot epidermis
Authors: Prin Fabrice , Logan Cairine , D'Souza Deana , Ensini Monica , Dhouailly Danielle
Published: February 2004

The dorsal and ventral scales of the chick foot can be distinguished morphologically and molecularly: the dorsal oblong overlapping scuta expressing both α and β keratins, and the ventral roundish nonprotruding reticula expressing only α keratins. The question arises how En‐1 and Lmx1, whose role in dorsoventral limb patterning has been well established, can affect skin morphogenesis, which occurs 8 to 12 days later. Forced expression of En‐1 or of Lmx1 in the hindlimb have, respectively, as expected, a ventralizing or a dorsalizing effect on skin, leading to the formation of either reticula‐type or scuta‐type scales on both faces. In both cases, however, the scales are abnormal and even glabrous skin without any scales at all may form. The normal inductive interactions between dermis and epidermis are disturbed after En‐1 or Lmx1 misexpression. Effectively, while Lmx1 endows the dermal precursors of the ventral region with scuta inducing ability, En‐1 blocks the competence of the dorsal epidermis to build scuta. Developmental Dynamics 229:564–578, 2004. © 2004 Wiley‐Liss, Inc.
ROCK inhibitor (Y27632) increases apoptosis and disrupts the actin cortical mat in embryonic avian corneal epithelium
Authors: Svoboda Kathy K.H. , Moessner Petra , Field Tamara , Acevedo Jesus
Published: February 2004

The embryonic chicken corneal epithelium is a unique tissue that has been used as an in vitro epithelial sheet organ culture model for over 30 years (Hay and Revel [1969] Fine structure of the developing Avian cornea. Basel, Switzerland: S. Karger A.G.). This tissue was used to establish that epithelial cells could produce extracellular matrix (ECM) proteins such as collagen and proteoglycans (Dodson and Hay [1971] Exp Cell Res 65:215–220; Meier and Hay [1973] Dev Biol 35:318–331; Linsenmayer et al. [1977] Proc Natl Acad Sci U S A 74:39–43; Hendrix et al. [1982] Invest Ophthalmol Vis Sci 22:359–375). This historic model was also used to establish that ECM proteins could stimulate actin reorganization and increase collagen synthesis (Sugrue and Hay [1981] J Cell Biol 91:45–54; Sugrue and Hay [1982] Dev Biol 92:97–106; Sugrue and Hay [1986] J Cell Biol 102:1907–1916). Our laboratory has used the model to establish the signal transduction pathways involved in ECM‐stimulated actin reorganization (Svoboda et al. [1999] Anat Rec 254:348–359; Chu et al. [2000] Invest Ophthalmol Vis Sci 41:3374–3382; Reenstra et al. [2002] Invest Ophthalmol Vis Sci 43:3181–3189). The goal of the current study was to investigate the role of ECM in epithelial cell survival and the role of Rho‐associated kinase (p160 ROCK, ROCK‐1, ROCK‐2, referred to as ROCK), in ECM and lysophosphatidic acid (LPA) ‐mediated actin reorganization. Whole sheets of avian embryonic corneal epithelium were cultured in the presence of the ROCK inhibitor, Y27632 at 0, 0.03, 0.3, 3, or 10 μM before stimulating the cells with either collagen (COL) or LPA. Apoptosis was assessed by Caspase‐3 activity assays and visualized with annexin V binding. The ROCK inhibitor blocked actin cortical mat reformation and disrupted the basal cell lateral membranes in a dose‐dependent manner and increased the apoptosis marker annexin V. In addition, an in vitro caspase‐3 activity assay was used to determine that caspase‐3 activity was higher in epithelia treated with 10 μM Y‐27632 than in those isolated without the basal lamina or epithelia stimulated with fibronectin, COL, or LPA. In conclusion, ECM molecules decreased apoptosis markers and inhibiting the ROCK pathway blocked ECM stimulated actin cortical mat reformation and increased apoptosis in embryonic corneal epithelial cells. Developmental Dynamics 229:579–590, 2004. © 2004 Wiley‐Liss, Inc.
Indian hedgehog and syndecans‐3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis
Authors: Shimo Tsuyoshi , Gentili Chiara , Iwamoto Masahiro , Wu Changshan , Koyama Eiki , Pacifici Maurizio
Published: February 2004

Hedgehog proteins exert critical roles in embryogenesis and require heparan sulfate proteoglycans (HS‐PGs) for action. Indian hedgehog (Ihh) is produced by prehypertrophic chondrocytes in developing long bones and regulates chondrocyte proliferation and other events, but it is not known whether it requires HS‐PGs for function. Because the HS‐PG syndecan‐3 is preferentially expressed by proliferating chondrocytes, we tested whether it mediates Ihh action. Primary chick chondrocyte cultures were treated with recombinant Ihh (rIhh‐N) in absence or presence of heparinase I or syndecan‐3 neutralizing antibodies. While rIhh‐N stimulated proliferation in control cultures, it failed to do so in heparinase‐ or antibody‐treated cultures. In reciprocal gain‐of‐function studies, chondrocytes were made to overexpress syndecan‐3 by an RCAS viral vector. Cells became more responsive to rIhh‐N, but even this response was counteracted by heparinase or antibody treatment. To complement the in vitro data, RCAS viral particles were microinjected in day 4–5 chick wing buds and effects of syndecan‐3 misexpression were monitored over time. Syndecan‐3 misexpression led to widespread chondrocyte proliferation and, interestingly, broader expression and distribution of Ihh. In addition, the syndecan‐3 misexpressing skeletal elements were short, remained cartilaginous, lacked osteogenesis, and exhibited a markedly reduced expression of collagen X and osteopontin, products characteristic of hypertrophic chondrocytes and bone cells. The data are the first to indicate that Ihh action in chondrocyte proliferation involves syndecan‐3 and to identify a specific member of the syndecan family as mediator of hedgehog function. Developmental Dynamics 229:607–617, 2004. © 2004 Wiley‐Liss, Inc.
Popeye domain containing gene 2 (Popdc2) is a myocyte‐specific differentiation marker during chick heart development
Authors: Breher Stephanie S. , Mavridou Eleftheria , Brenneis Christian , Froese Alexander , Arnold Hans‐Henning , Brand Thomas
Published: February 2004

The Popeye domain containing (popdc) genes constitute a novel gene family encoding proteins of the plasma membrane in muscle cells, with three N‐terminal transmembrane domains and a cytoplasmic carboxy terminus. In vertebrates, three members of the Popdc gene family have been described. However, in the chick system only two cDNAs, Popdc1 and Popdc3, have been cloned previously. By screening a chick expressed sequence tag database, we report here the identification of five alternatively spliced chick Popdc2 cDNAs with different carboxy termini. Northern blot analysis revealed expression of Popdc2 predominantly in the myocardium and weaker expression in skeletal muscle. By whole‐mount in situ hybridization, chick Popdc2 was first detected at Hamburger and Hamilton (HH) stage 7 within the anterior part of the heart fields. In the tubular heart, atrial and ventricular precursor cells stained positively for Popdc2. Weaker expression was observed in myocardium of the outflow tract and sinus venosus. By HH stage 18, the outer curvature myocardium was strongly stained, whereas expression in myocardium of the inner curvature was negligible. Popdc2 expression was absent from the endocardium and propepicardial organ. At HH stage 36, Popdc2 expression was confined to the compact layer myocardium. In addition to the heart, Popdc2 expression was also observed in the myotome and in the muscle‐forming fields of the limbs. Our results indicate that Popdc2 is highly expressed in the developing heart and may serve as a novel marker of myocardial differentiation in the chick embryo. Developmental Dynamics 229:695–702, 2004. © 2004 Wiley‐Liss, Inc.
Precocious terminal differentiation of premigratory limb muscle precursor cells requires positive signalling
Authors: Venters Sara J. , Argent Rebecca E. , Deegan Fiona M. , Perez‐Baron Gina , Wong Ted S. , Tidyman William E. , Denetclaw Wilfred F. , Marcelle Christophe , Bronner‐Fraser Marianne , Ordahl Charles P.
Published: February 2004

The timing of myogenic differentiation of hypaxial muscle precursor cells in the somite lags behind that of epaxial precursors. Two hypotheses have been proposed to explain this delay. One attributes the delay to the presence of negative‐acting signals from the lateral plate mesoderm adjacent to the hypaxial muscle precursor cells located in the ventrolateral lip of the somitic dermomyotome (Pourquié et al. [1995] Proc. Natl. Acad. Sci. USA 92:3219–3223). The second attributes the delay to an absence of positive‐acting inductive signals, similar to those from the axial structures that induce epaxial myotome development (Pownall et al. [1996] Development 122:1475–1488). Because both studies relied principally upon changes in the expression pattern of mRNAs specific to early muscle precursor cell markers, we revisited these experiments using two methods to assess muscle terminal differentiation. First, injection of fluorescent dyes before surgery was used to determine whether ventrolateral lip cells transform from epithelial cells to elongated myocytes. Second, an antibody to a terminal differentiation marker and a new monoclonal antibody that recognises avian and mammalian Pax3 were used for immunohistochemistry to assess the transition from precursor cell to myocyte. The results support both hypotheses and show further that placing axial structures adjacent to the somite ventrolateral lip induces an axial pattern of myocyte terminal differentiation and elongation. Developmental Dynamics 229:591–599, 2004. © 2004 Wiley‐Liss, Inc.
Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia
Authors: Nelson Branden R. , Sadhu Meru , Kasemeier Jennifer C. , Anderson Lawrence W. , Lefcort Frances
Published: February 2004

The dorsal root ganglia (DRG) derive from a population of migrating neural crest cells that coalesce laterally to the neural tube. As the DRG matures, discrete cell types emerge from a pool of differentiating progenitor cells. To identify genes that regulate sensory genesis and differentiation, we have designed screens to identify members from families of known regulatory molecules such as receptor tyrosine kinases, and generated full‐length and subtractive cDNA libraries between immature and mature DRG for identifying novel genes not previously implicated in DRG development. Several genes were identified in these analyses that belong to important regulatory gene families. Quantitative PCR confirmed differential expression of candidate cDNAs identified from the subtraction/differential screening. In situ hybridization further validated dynamic expression of several cDNAs identified in our screens. Our results demonstrate the utility of combining specific and general screening approaches for isolating key regulatory genes involved in the genesis and differentiation of discrete cell types and tissues within the classic embryonic chick model system. Developmental Dynamics 229:618–629, 2004. © 2004 Wiley‐Liss, Inc.
Axis I comorbidity onset and parasuicide in women with eating disorders
Authors: Wildman Prudence , Lilenfeld Lisa R.R. , Marcus Marsha D.
Published: February 2004

Objective

We examined differences in the onset pattern of comorbid disorders in eating‐disordered women with and without a history of parasuicide to elucidate potential etiologic differences between the two groups.

Methods

Fifty‐four women with a current or past eating disorder partcipated. Of these women, 27 had a history of suicide attempts and self‐injury and 27 had no history of suicide attempts or self‐injury. The age and pattern of onset for the eating disorder relative to comorbid major depression, anxiety disorder, and substance use disorder were compared between the groups.

Results

The onset of major depression and anxiety disorders occurred at a younger age in the parasuicidal group. In addition, the onset of major depression in the parasuicidal group occurred significantly more often before the onset of the eating disorder.

Discussion

The eating disorder may be secondary to a mood disturbance in women with parasuicidal histories. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 190–197, 2004.
Body image and eating disturbance in India: Media and interpersonal influences
Authors: Shroff Hemal , Thompson J. Kevin
Published: February 2004

Objective

The current study was designed to examine the relationships among the variables of body mass index (BMI), interpersonal teasing, media internalization, body dissatisfaction, and drive for thinness in samples of young adult and middle school females from India.

Method

Ninety‐six adolescent and 93 adult females from Bombay, India, completed measures of body dissatisfaction, restriction, teasing history, and internalization of media images. Correlational and path analytic procedures were used to examine the data.

Results

Path analyses indicated that teasing and internalization mediated the effect of BMI on body dissatisfaction and in certain cases influenced drive for thinness.

Discussion

These findings replicate and extend previous work with U.S., Australian, and Swedish samples, suggesting that there are similar potential risk factors, cross‐culturally, that may explain the development of eating and shape‐related problems. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 198–203, 2004.
Parental bonding and bulimic psychopathology: The mediating role of mistrust/abuse beliefs
Authors: Meyer Caroline , Gillings Kirsty
Published: February 2004

Objective

To determine whether the previously reported relationship between parental bonding and bulimic psychopathology is mediated by the development of unhealthy core beliefs.

Method

One hundred and two nonclinical women completed the Parental Bonding Instrument, the short form of the Young Schema Questionnaire, and the Bulimic Investigatory Test, Edinburgh.

Results

Mistrust/abuse beliefs were found to be a partial mediator in the relationship between paternal overprotection and the severity of bulimic attitudes.

Conclusions

The findings suggest that the development of mistrust/abuse beliefs is important in determining the effect that paternal overprotection has on bulimic attitudes. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 229–233, 2004.
Effect of social desirability on adolescent girls' responses to an eating disorders prevention program
Authors: Tilgner Linda , Wertheim Eleanor H. , Paxton Susan J.
Published: February 2004

Objective

The current study examined whether a social desirability response bias is a source of measurement error in prevention research.

Method

Six hundred and seventy‐seven female students in Grade 7 (n = 345) and Grade 8 (n = 332) were divided into either an intervention condition, in which participants watched a videotape promoting body acceptance and discouraging dieting and then discussed issues related to the video, or a control condition. Questionnaires were completed at baseline, postintervention, and at 1‐month follow‐up.

Results

Social desirability scores were correlated at a low but significant level with baseline body dissatisfaction, drive for thinness, bulimic tendencies, intention to diet, and size discrepancy for intervention participants. Social desirability did not correlate significantly with change over time in the outcome measures.

Discussion

The findings suggested that changes in girls' self‐reports related to a prevention program were relatively free of social desirability response bias. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 211–216, 2004.
Night eating syndrome among nonobese persons
Authors: Marshall Heidi M. , Allison Kelly C. , O'Reardon John P. , Birketvedt Grethe , Stunkard Albert J.
Published: February 2004

Objective

To compare the characteristics of obese persons with the night eating syndrome (NES) with those of nonobese persons with the NES.

Methods

Eighty subjects (40 with a body mass index [BMI] greater than 30 and 40 with a BMI less than 25) identified themselves on a website for the Night Eating Questionnaire (NEQ) as suffering from the NES. The responses of the 40 obese website subjects were compared with 21 obese persons with the NES who had undergone face‐to‐face interviews. The responses on the NEQ of the 40 obese and the 40 non‐obese website subjects were then compared.

Results

There was no difference in the NEQ results of the 40 website obese subjects and 21 obese night eaters who had undergone face‐to‐face interviews. The responses of these same 40 obese subjects showed very little difference compared with those of the 40 nonobese subjects. The major difference between the two groups was the considerable younger age of the normal‐weight NES subjects.

Discussion

The striking similarity in the characteristics between obese and nonobese subjects with the NES indicates that this disorder, considered until now to occur primarily among obese persons, also occurs among nonobese persons. The younger age of the nonobese subjects suggests that the NES may contribute to the development of obesity. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 217–222, 2004.
Randomized controlled trial of warming in anorexia nervosa
Authors: Birmingham C. Laird , Gutierrez Emilio , Jonat Lee , Beumont Peter
Published: February 2004

Objective

To determine if warming therapy increases the rate of weight gain in patients with anorexia nervosa (AN) who are hospitalized for refeeding.

Method

Patients admitted to an eating disorders unit of a university teaching hospital were randomized to treatment and control arms. All patients wore a heating vest for 3 hr a day for 21 days. In the experimental arm, the vest was set to medium heat and in the control arm it was set in the off position.

Results

Twenty‐one females were recruited. They had an average age of 28.4 ± 6.6 years, a body mass index (BMI) of 17.7 ± 2.8, and the duration of AN lasted 13.6 ± 6.7 years. Ten subjects were randomized to the treatment arm and 11 to the control arm. Of the 18 completers, there was no difference in the change in BMI.

Discussion

Our study did not demonstrate an increase in the rate of weight gain with warming. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 234–238, 2004.
Gender identity disorder and anorexia nervosa in male monozygotic twins
Authors: Hepp Urs , Milos Gabriella , Braun‐Scharm Hellmuth
Published: February 2004

Objective

Male identical twins with gender identity disorder (GID) in childhood and anorexia nervosa (AN) are presented. Etiologic aspects and the relationship among gender identity, sexual orientation, body dissatisfaction, and AN are discussed.

Method

Case reports and a review of the literature are reported.

Results

In childhood, both twins showed an atypical gender behavior. Whereas one of the twins later developed a transsexual gender identity and asked for sex reassignment, the other developed a male identity but his appearance and clothing are effeminate. According to their biologic sex, they are concordant in regard to their homosexual orientation. In adolescence, both developed AN. Monozygotism was proved by DNA analysis.

Discussion

GID in childhood could be at least partly hereditary, whereas the development of the later phenotype of the gender identification is more determined by environmental factors. GID might be a risk factor for the development of AN. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 239–243, 2004.
Looking good—family focus on appearance and the risk for eating disorders
Authors: Davis Caroline , Shuster Barbara , Blackmore Elizabeth , Fox John
Published: February 2004

Objective

Evidence suggests that eating‐disordered families are overly concerned with social appearance and physical attractiveness. However, some argue that parental values are not sufficient to produce disordered eating in their offspring unless combined with certain third‐factor effects of the child such as a psychological or biologic vulnerability. We tested this hypothesis by predicting that proneness to anxiety (neuroticism) and a family appearance focus would relate interactively (after controlling for body size) to a measure of weight preoccupation.

Method

Data from 158 healthy young women were used in the analyses.

Results

Statistical analyses confirmed our hypothesis in a multiple regression model that accounted for 42% of the variance in weight preoccupation.

Discussion

Findings support the view that family risk factors have a more potent influence on young women who are easily made anxious—perhaps because they are more sensitive to, or more likely to internalize, pressures and expectations to conform to family values. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 136–144, 2004.
Measuring eating concerns in Black and White adolescent girls
Authors: Franko Debra L. , Striegel‐Moore Ruth H. , Barton Bruce A. , Schumann Barbara C. , Garner David M. , Daniels Stephen R. , Schreiber George B. , Crawford Patricia B.
Published: February 2004

Objective

Few instruments exist to measure eating concerns in adolescent girls from diverse ethnic backgrounds.

Methods

A Children's version of the Eating Disorder Inventory (EDI‐C) has been under development for several years and was designed to be more appropriate for younger children with lower reading levels. However, little is known about the validity of this instrument. The current study reports on the factor structure of an early version of the EDI‐C using nonclinical samples of 1,073 White and 1,155 Black girls (ages 11–12).

Results

Factor analysis resulted in an eight‐factor solution for each group that included a weight concerns factor and an emotional distress factor. For Black girls only, the positively worded items from the Body Dissatisfaction subscale loaded on a separate factor. Four of five factors were similar to the original EDI subscales (Bulimia, Interpersonal Distrust, Maturity Fears, and Perfectionism), although the latter was unique to White girls.

Discussion

The factor structure was generally similar for Black and White girls, although the separate body satisfaction factor and lack of shared variance for the perfectionism factor for Black girls suggest that EDI data obtained from ethnic minority samples may need to be interpreted cautiously. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 179–189, 2004.
Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients
Authors: Le Rond Solène , Le Maoult Joël , Créput Caroline , Menier Catherine , Deschamps Marina , Le Friec Gaëlle , Amiot Laurence , Durrbach Antoine , Dausset Jean , Carosella Edgardo D. , Rouas‐Freiss Nathalie
Published: February 2004

HLA‐G displays immunotolerogenic properties towards the main effector cells involved in graft rejection through inhibition of NK‐ and CTL‐mediated cytolysis and CD4+ T cell alloproliferation. HLA‐G expression is restricted in healthy tissues to trophoblast and thymus but is extended to various tissues under pathological conditions. HLA‐G was detected in allograft biopsies and sera from transplanted patients who displayed a better graft acceptance. However, the cells involved in such de novo expression of HLA‐G remain to be characterized. By flow cytometry and confocal microscopy, we demonstrated that, following allogeneic stimulation in vitro, both CD4+ and CD8+ T cell subsets can express membrane‐bound HLA‐G1 and/or soluble HLA‐G5molecules. Such HLA‐G1/‐G5 expression is regulated at the transcriptional level. Soluble HLA‐G5 could be detected by using a novel monoclonal antibody, 5A6G7, specific for the intron 4‐retaining sequence of HLA‐G5. Finally, the biological relevance of these data was provided by analysis of transplanted patients in whom we identified both CD4+ and CD8+ T cells expressing HLA‐G. The HLA‐G‐positive T cells we describe here may constitute a cellular source of HLA‐G after allotransplantation and may be involved in the improved graft acceptance which is observed in HLA‐G‐positive transplanted patients.
Lowering the affinity between antigen and the B cell receptor can enhance antigen presentation
Authors: Brooks Katie , Knight Andrew M.
Published: February 2004

The B cell receptor (BCR) enables antigen‐specific B cells to bind, internalize and target antigens for processing into small peptide fragments. These epitopes are then expressed on the plasmamembrane in association with MHC class II molecules for recognition by CD4+ T cells. The affinity of the interaction between the BCR and antigen plays an important part in determining T cell epitope generation. In this report we provide evidence that the efficiency of antigen presentation by specific B cells does not need to be directly proportional to antigen/BCR affinity. We show that increased presentation can result from lowering the affinity of the antigen/BCR interaction. This finding suggests a novel mechanism by which B cells can recruit T cell help and obtain survival signals. Activation of these cells may have consequences for the generation of the B cell repertoire.
Demonstration of strong enterobacterial reactivity of CD4+CD25– T cells from conventional and germ‐free mice which is counter‐regulated by CD4+CD25+ T cells
Authors: Gad Monika , Pedersen Anders Elm , Kristensen Nanna N. , Claesson Mogens H.
Published: February 2004

Unfractionated CD4+ T cells from the gut‐associated lymphoid tissue (GALT) and peripheral lymph nodes are unresponsive when exposed to enterobacterial antigens in vitro. Under similar conditions, CD4+ T cells depleted in vivo or in vitro of CD4+CD25+ T cells proliferate extensively. The CD4+CD25– T cell reactivity depends on MHC class II presentation, specific TCR stimulation, CD4 ligation, and antigen processing by antigen‐presenting cells. The CD4+CD25– T cells respond to autologousand heterologous enterobacterial antigens, but not to antigens from the feces of germ‐free mice. Surprisingly, CD4+CD25– T cells obtained from the GALT of germ‐free mice also proliferate when exposed to enterobacterial antigens, and adding back the conventional or germ‐free CD4+CD25+ T cells to the enteroantigen‐stimulated CD4+CD25– T cells abolishes proliferation. As judged from carboxyfluorescein diacetate succinimidyl ester‐labeling experiments, 4–5% of the CD4+CD25– T cells respond to enteroantigen. The data show for the first time that CD4+CD25– T cells with reactivity towards the enterobacterial flora and regulatory CD4+CD25+ T cells are present in both conventional and germ‐free mice. The data suggest that a significant proportion of the peripheral pool of CD4+CD25– T cells express anti‐enterobacterial reactivity, which, due to the presence of regulatory CD4+CD25+ T cells, is kept in a quiescent state.
The RhoA‐ and CDC42‐specific exchange factor Dbs promotes expansion of immature thymocytes and deletion of double‐positive and single‐positive thymocytes
Authors: Klinger Mark B. , Guilbault Benoit , Kay Robert J.
Published: February 2004

Specific members of the Rho family of GTPases exert unique influences on thymocyte proliferation, differentiation and deletion. Dbs is a guanine nucleotide exchange factor which is expressed throughout thymocyte development and is able to activate the Rho family GTPases CDC42, RhoA and RhoG. Transgenic mice expressing an activated form of Dbs had increased numbers of double‐negative thymocytes. The Dbs transgene promoted expansion of double‐negative thymocytes in the absence of pre‐TCR, but had no effect on pre‐TCR‐dependent differentiation of double‐negative thymocytes into double‐positive thymocytes. Transgenic double‐positive thymocytes were proliferative in vivo, but were also susceptible to apoptosis in vivo and in vitro. The transgenic single‐positive thymocytes had attenuated proliferative responses following TCR ligation, and were depleted rather than expanded during culture in the presence of anti‐CD3. When expressing a positively selectable TCR, transgenic double‐positive thymocytes were increased in number and activated, but the output of single‐positive thymocytes was reduced. Transgenic double‐positive thymocytes were acutely sensitive to deletion by TCR ligation in vivo. These results indicate that activation of Dbs has the potential to promote proliferation throughout thymocyte development, but also sensitizes double‐positive and single‐positive thymocytes to deletion.
Non‐redundancy of cytidine deaminases in class switch recombination
Authors: Fugmann Sebastian D. , Rush James S. , Schatz David G.
Published: February 2004

Class switch recombination (CSR), somatic hypermutation, and gene conversion are immunoglobulin diversification mechanisms that are strictly dependent on the activity of the activation‐inducedcytidine deaminase (AID). The precise role and substrate(s) of AID in these processes remain to be well defined. The closest homologue of AID is APOBEC‐1, a bona fide mRNA‐editing enzyme, which shares with AID the ability to deaminate cytidines within single‐stranded DNA in vitro and in prokaryotic cells. To determine whether APOBEC‐1 can therefore substitute for AID in activated B cells, we expressed human AID, a catalytic mutant thereof, and rat APOBEC‐1 in AID‐deficient murine B cells. Whereas AID rescued CSR, neither the inactive mutant nor APOBEC‐1 could complement AID deficiency. This indicates that cytidine deaminase activity is necessary but not sufficient to initiate CSR, and suggests that AID is specifically targeted to its cognate substrate, the immunoglobulin genes or a distinct mRNA, by an as‐yet‐unknown mechanism.
The CD8+ T cell repertoire against Her‐2/neu antigens in neu transgenic mice is of low avidity with antitumor activity
Authors: Lustgarten Joseph , Dominguez Ana Lucia , Cuadros Camilo
Published: February 2004

The majority of tumor‐associated antigens are aberrantly expressed or overexpressed normal gene products. Therefore, mechanisms responsible for self tolerance dampen immune responses against these antigens. To evaluate the effect that tolerance has on the immune responses against tumor antigens, we characterized the CD8+ T cell responses in neu mice. T cell responses against theA2.1/neu p369–377 and p773–782 peptides were evaluated in neu mice that were crossed with A2.1/Kb transgenic mice (A2×neu). Tetramer binding and cytotoxic activity demonstrate that, compared to CTL from A2.1/Kb×FVB wild‐type mice (A2×FVB), CD8+ T cells from A2×neu mice were of lower avidity for the peptides. Despite the fact that A2×neu mice are tolerant, multipleimmunizations with DC pulsed with the p369–377 or p773–782 peptides in the presence of IL‐2 retarded tumor growth in A2×neu mice, and immunizations in combination with the anti‐OX40 mAb further enhanced the antitumor response. Taken together, these data indicate that low‐avidity T cells for neu antigens persisting in A2×neu mice have the capacity to develop antitumor responses as long as they are provided with efficient costimulation. These results underscore the potential role of low‐avidity T cells in antitumor immunity and may offer an important component for vaccination immunotherapies.
MHC class II‐independent CD25+ CD4+ CD8α β+ α β T cells attenuate CD4+ T cell‐induced transfer colitis
Authors: Krajina Tamara , Leithäuser Frank , Reimann Jörg
Published: February 2004

CD4+ α β T cell populations that develop in mice deficient in MHC class II (through ‘knockout’ of either the Aα, or the Aβ chain of the I‐Ab molecule) comprise a major ‘single‐positive’ (SP) CD4+ CD8– subset (60–90%) and a minor ‘double‐positive’ (DP) CD4+ CD8α β+ subset (10–40%). Many DP T cells found in spleen, mesenteric lymph nodes (MLN) and colonic lamina propria (cLP) express CD25, CD103 and Foxp3. Adoptive transfer of SP but not DP T cells from Aα–/– or Aβ–/– B6 mice into congenic RAG–/– hosts induces colitis. Transfer of SP T cells repopulates the host with only SP T cells; transfer of DP T cells repopulates the host with DP and SP T cells. Anti‐CD25 antibody treatment of mice transplanted with DP T cells induces severe, lethal colitis; anti‐CD25 antibody treatment of mice transplanted with SP T cells further aggravates the course of severe colitis. Hence, regulatory CD25+ T cells within (or developing from) the DP T cell population of MHC class II‐deficient mice control the colitogenic potential of CD25– CD4+ T cells.