bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) Sequentially Upregulates Nitric Oxide and Prostanoid Production in Primary Human Endothelial Cells
Authors: Zauli Giorgio , Pandolfi Assunta , Gonelli Arianna , Di Pietro Roberta , Guarnieri Simone , Ciabattoni Giovanni , Rana Rosalba , Vitale Marco , Secchiero Paola
Published: April 2003

Endothelial cells express tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptors, but the function of TRAIL in endothelial cells is not completely understood. We explored the role of TRAIL in regulation of key intracellular signal pathways in endothelial cells. The addition of TRAIL to primary human endothelial cells increased phosphorylation of endothelial nitric oxide synthase (eNOS), NOS activity, and NO synthesis. Moreover, TRAIL induced cell migration and cytoskeleton reorganization in an NO-dependent manner. TRAIL did not activate the NF-κB or COX-2 pathways in endothelial cells. Instead, TRAIL increased prostanoid production (PGE
2
=PGI
2
>TXA
2
), which was preferentially inhibited by the COX-1 inhibitor SC-560. Because NO and prostanoids play a crucial role in the state of blood vessel vasodilatation and angiogenesis, our data suggest that TRAIL might play an important role in endothelial cell function.
NFAT Transcription Factors Are Critical Survival Factors That Inhibit Cardiomyocyte Apoptosis During Phenylephrine Stimulation In Vitro
Authors: Pu William T. , Ma Qing , Izumo Seigo
Published: April 2003

Biomechanical stress on the heart results in activation of numerous signaling cascades, leading to cardiomyocyte hypertrophy, apoptosis, and ultimately, heart failure. The Ca
2+
-dependent phosphatase calcineurin is an essential mediator of cardiac hypertrophy, and in most but not all studies, calcineurin inhibition attenuated cardiac hypertrophy in vivo. However, calcineurin inhibition has been reported to have adverse effects on cardiac remodeling and cardiomyocyte apoptosis. Calcineurin regulates the activity of a number of downstream targets, including the transcription factors NFAT, MEF2, and NF-κB, and the apoptotic factor Bad. To evaluate the contribution of NFAT activation by calcineurin to cardiomyocyte responses to hypertrophic stimulation, we used adenovirus to express VIVIT, a selective peptide inhibitor of calcineurin-mediated NFAT activation. We found that selective NFAT inhibition during phenylephrine stimulation inhibited hypertrophy but resulted in increased cardiomyocyte apoptosis. In contrast, nonselective inhibition of calcineurin by cyclosporin A did not cause cardiomyocyte apoptosis after phenylephrine stimulation. Cyclosporin A suppressed the effect of VIVIT on cardiomyocyte apoptosis. These results demonstrate that during phenylephrine stimulation calcineurin activates both pro- and antiapoptotic pathways in cardiomyocytes, and that NFAT activity is a critical component of the antiapoptotic pathway that regulates whether the outcome of calcineurin activation is cardiomyocyte apoptosis or survival.
PREACHING FOR A RESPONSE? JONAH'S MESSAGE TO THE NINEVITES RECONSIDERED
Authors:   Moberly
Published: April 2003

Jonah's message to the Ninevites is unusual in specifying a time limit before judgment comes. But while the MT and most manuscripts read "forty days" the LXX reads "three days". The history of interpretation of both "forty" and "three" is briefly surveyed before a fresh proposal is offered. The LXX represents a perception of what would be appropriate for Jonah to say, on the assumption that his message is faithful to his commission. The MT depicts a Jonah who does not want the Ninevites to respond.
THE DISTRIBUTION OF MESSAGES IN THE KINGDOM OF JUDAH IN LIGHT OF THE LACHISH OSTRACA
Authors: Na'aman Nadav
Published: April 2003

The article deals with the problem of communication between the capital city of Jerusalem and the kingdom's districts and the distribution of messages from the centre to the periphery in the late First Temple period. It calls attention to the Lachish ostraca that illustrate the ways in which news was spread among officials of the Kingdom of Judah. Letters played an important role in the communication and local officials were accustomed to share letters that they received with neighbouring colleagues. Based on the information they received the officials and local elite were aware of the internal and external policies of the king and his court and were able to form their own opinion on the main problems debated at the time in the court of Jerusalem.
A REASSESSMENT OF THE RADICAL NATURE OF JOB'S ETHIC IN JOB XXXI 13-15
Authors: Neville Richard
Published: April 2003

Commentators have concluded that Job xxxi 13-15 represents an ethical high point in the Old Testament and have praised Job for it. Typically Job is seen as recognising the rights of his slaves on the basis that they are his equals as human beings. Given this understanding of Job's words, the high praise seems justified. However, there are reasons to doubt that this is what Job is saying. In the context of his protestation of innocence (Job xxxi) it is doubtful he would defend himself against an accusation so radical that no one would have thought to accuse him of the offence. It would also be out of character for the sages to advocate a revolutionary ethic. Furthermore, it is troubling that there is no consensus on how to derive the proposed meaning from the text, and when the various strategies are investigated they are unconvincing. An alternative interpretation is offered which looks to the language and ideology of personal religion in order to understand the significance of Job's reference to the fact that he and his servants were made in the womb by the same God.
THE PROPHECY FOR "EVERLASTING COVENANT" (JEREMIAH XXXII 36-41): AN EXILIC ADDITION OR A DEUTERONOMISTIC REDACTION?
Authors: Rom-Shiloni Dalit
Published: April 2003

This paper draws attention to the exact relationship between the prophecy for "everlasting covenant" (Jer. xxxii 36-41) and the words of the prophet and his ideological agenda on the one hand, and the redactional level of the Book of Jeremiah on the other. Examination of the genre of the prophetical unit presents it to be a quasi-disputation-speech, and a further testimony to the exilic voices in Jeremiah on the controversy between the Jehoiachin exiles and the remnant. A close reading of the verses gives evidence to five different ways of dependence on and independence from both the words of the prophet and the redactional additions to Jeremiah. Hence, this prophecy demonstrates the composition of a new independent prophecy within exilic context, and thus adduces the question whether the exilic material within Jeremiah can still be restricted to Deuteronomistic circles.
An urbilaterian origin of the tripartite brain: developmental genetic insights fromDrosophila
Authors: Hirth Frank , Kammermeier Lars , Frei Erich , Walldorf Uwe , Noll Markus , Reichert Heinrich
Published: April 2003

Studies on expression and function of key developmental control genes suggest that the embryonic vertebrate brain has a tripartite ground plan that consists of a forebrain/midbrain, a hindbrain and an intervening midbrain/hindbrain boundary region, which are characterized by the specific expression of the Otx, Hox and Pax2/5/8 genes, respectively. We show that the embryonic brain of the fruitfly Drosophila melanogasterexpresses all three sets of homologous genes in a similar tripartite pattern. Thus, a Pax2/5/8 expression domain is located at the interface of brain-specific otd/Otx2 and unpg/Gbx2 expression domains anterior to Hox expression regions. We identify this territory as the deutocerebral/tritocerebral boundary region in the embryonic Drosophila brain. Mutational inactivation of otd/Otx2 and unpg/Gbx2 result in the loss or misplacement of the brain-specific expression domains of Pax2/5/8 and Hox genes. In addition, otd/Otx2 and unpg/Gbx2 appear to negatively regulate each other at the interface of their brain-specific expression domains. Our studies demonstrate that the deutocerebral/tritocerebral boundary region in the embryonic Drosophila brain displays developmental genetic features similar to those observed for the midbrain/hindbrain boundary region in vertebrate brain development. This suggests that a tripartite organization of the embryonic brain was already established in the last common urbilaterian ancestor of protostomes and deuterostomes.
The orientation of cell division influences cell-fate choice in the developing mammalian retina
Authors: Cayouette Michel , Raff Martin
Published: April 2003

Asymmetric segregation of cell-fate determinants during cell division plays an important part in generating cell diversity in invertebrates. We showed previously that cells in the neonatal rat retina divide at various orientations and that some dividing cells asymmetrically distribute the cell-fate determinant Numb to the two daughter cells. Here, we test the possibility that such asymmetric divisions contribute to retinal cell diversification. We have used long-term videomicroscopy of green-fluorescent-protein (GFP)-labeled retinal explants from neonatal rats to visualize the plane of cell division and follow the differentiation of the daughter cells. We found that cells that divided with a horizontal mitotic spindle, where both daughter cells should inherit Numb, tended to produce daughters that became the same cell type, whereas cells that divided with a vertical mitotic spindle, where only one daughter cell should inherit Numb,tended to produce daughters that became different. Moreover, overexpression of Numb in the dividing cells promoted the development of photoreceptor cells at the expense of interneurons and Müller glial cells. These findings indicate that the plane of cell division influences cell-fate choice in the neonatal rat retina and support the hypothesis that the asymmetric segregation of Numb normally influences some of these choices.
Xenopus Cyr61regulates gastrulation movements and modulates Wnt signalling
Authors: Latinkic B. V. , Mercurio S. , Bennett B. , Hirst E. M. A. , Xu Q. , Lau L. F. , Mohun T. J. , Smith J. C.
Published: April 2003

Cyr61 is a secreted, heparin-binding, extracellular matrix-associated protein whose activities include the promotion of adhesion and chemotaxis, and the stimulation of fibroblast and endothelial cell growth. Many, if not all,of these activities of Cyr61 are mediated through interactions with integrins. We explore the role of Cyr61 in the early development of Xenopus laevis. Gain- and loss-of-function experiments show that Xcyr61 is required for normal gastrulation movements. This role is mediated in part through the adhesive properties of Xcyr61 and its related ability to modulate assembly of the extracellular matrix. In addition, Xcyr61 can, in a context-dependent manner, stimulate or inhibit signalling through the Wnt pathway. These properties of Xcyr61 provide a mechanism for integrating cell signalling, cell adhesion and cell migration during gastrulation.
Neural crest contributions to the lamprey head
Authors: McCauley David W. , Bronner-Fraser Marianne
Published: April 2003

The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.
Ash1a and Neurogenin1 function downstream of Floating head to regulate epiphysial neurogenesis
Authors: Cau Elise , Wilson Stephen W.
Published: April 2003

The homeodomain transcription factor Floating head (Flh) is required for the generation of neurones in the zebrafish epiphysis. It regulates expression of two basic helix loop helix (bHLH) transcription factor encoding genes, ash1a (achaete/scute homologue 1a) and neurogenin1 (ngn1), in epiphysial neural progenitors. We show that ash1a and ngn1 function in parallel redundant pathways to regulate neurogenesis downstream of flh. Comparison of the epiphysial phenotypes of flh mutant and of ash1a/ngn1double morphants reveals that reduced expression of ash1a and ngn1 can account for most of the neurogenesis defects in the flh-mutant epiphysis but also shows that Flh has additional activities. Furthermore, different cell populations show different requirements for ash1a and ngn1 within the epiphysis. These populations do not simply correspond to the two described epiphysial cell types: photoreceptors and projection neurones. These results suggest that the genetic pathways that involve ash1a and ngn1 are common to both neuronal types.
Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130
Authors: Ruiz Sergio , Segrelles Carmen , Bravo Ana , Santos Mirentxu , Perez Paloma , Leis Hugo , Jorcano Jose L. , Paramio Jesús M.
Published: April 2003

The functions of p107 and p130, members of the retinoblastoma family,include the control of cell cycle progression and differentiation in several tissues. Our previous studies suggested a role for p107 and p130 in keratinocyte differentiation in vitro. We now extend these data using knockout animal models. We found impaired terminal differentiation in the interfollicular keratinocytes of p107/p130-double-null mice epidermis. In addition, we observed a decreased number of hair follicles and a clear developmental delay in hair, whiskers and tooth germs. Skin grafts of p107/p130-deficient epidermis onto NOD/scid mice showed altered differentiation and hyperproliferation of the interfollicular keratinocytes,thus demonstrating that the absence of p107 and p130 results in the deficient control of differentiation in keratinocytes in a cell-autonomous manner. Besides normal hair formation, follicular cysts, misoriented and dysplastic follicles, together with aberrant hair cycling, were also observed in the p107/p130 skin transplants. Finally, the hair abnormalities in p107/p130-null skin were associated with altered Bmp4-dependent signaling including decreasedΔNp63 expression. These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions.
Zebrafishfoxione modulates cellular responses to Fgf signaling required for the integrity of ear and jaw patterning
Authors: Nissen Robert M. , Yan Jizhou , Amsterdam Adam , Hopkins Nancy , Burgess Shawn M.
Published: April 2003

We identified four insertional alleles of foxi one (foo),an embryonic lethal mutation in zebrafish that displays defects in both otic placode and the jaw. In foo/foo embryos the otic placode is split into two smaller placodes and mutant embryos show a dorsoventral (DV)cartilage defect manifested as a reduced hyomandibular and reduced third and fourth branchial arches. We identified foxi one (foo), the zebrafish ortholog of Foxi1 (FREAC6, FKHL10, HFH-3, Fkh10) and a member of the forkhead domain transcriptional regulator family, as the gene mutated in foo/foo embryos. foo is expressed in otic placode precursor cells, and foo/foo embryos lack placodal pax8 expression and have disorganized otic expression of pax2.1 and dlx3. Third stream neural crest cell migration, detected by dlx2 and krox20 expression, is aberrant in that it invades the otic placode territory. foo is expressed in pharyngeal pouch endoderm and is required for pouch expression of pax8 and proper patterning of other markers in the pouch such as nkx2.3. In foo/foo embryos, we observed a failure to maintain fgf3 expression in the pouches,followed by apoptosis of neural crest cells in adjacent arches. We conclude that foo expression is essential for pax8 expression probably downstream of Fgf signaling in a conserved pathway jointly required for integrity of patterning in the otic placode and pharyngeal pouches. We propose that correct placement of survival/proliferation cues is essential for shaping the pharyngeal cartilages and that evolutionary links between jaw and ear formation can be traced to Fgf-Foxi1-Pax8 pathways.
Splyregulation of sphingolipid signaling molecules is essential for Drosophila development
Authors: Herr Deron R. , Fyrst Henrik , Phan Van , Heinecke Karie , Georges Rana , Harris Greg L. , Saba Julie D.
Published: April 2003

Sphingosine-1-phosphate is a sphingolipid metabolite that regulates cell proliferation, migration and apoptosis through specific signaling pathways. Sphingosine-1-phosphate lyase catalyzes the conversion of sphingosine-1-phosphate to ethanolamine phosphate and a fatty aldehyde. We report the cloning of the Drosophila sphingosine-1-phosphate lyase gene (Sply) and demonstrate its importance for adult muscle development and integrity, reproduction and larval viability. Splyexpression is temporally regulated, with onset of expression during mid-embryogenesis. Sply null mutants accumulate both phosphorylated and unphosphorylated sphingoid bases and exhibit semi-lethality, increased apoptosis in developing embryos, diminished egg-laying, and gross pattern abnormalities in dorsal longitudinal flight muscles. These defects are corrected by restoring Sply expression or by introduction of a suppressor mutation that diminishes sphingolipid synthesis and accumulation of sphingolipid intermediates. This is the first demonstration of novel and complex developmental pathologies directly linked to a disruption of sphingolipid catabolism in metazoans.
Bifunctional action of ephrin-B1 as a repellent and attractant to control bidirectional branch extension in dorsal-ventral retinotopic mapping
Authors: McLaughlin Todd , Hindges Robert , Yates Paul A. , O'Leary Dennis D. M.
Published: April 2003

We report that the EphB receptor ligand, ephrin-B1, may act bifunctionally as both a branch repellent and attractant to control the unique mechanisms in mapping the dorsal-ventral (DV) retinal axis along the lateral-medial (LM)axis of the optic tectum. EphB receptors are expressed in a low to high DV gradient by retinal ganglion cells (RGCs), and ephrin-B1 is expressed in a low to high LM gradient in the tectum. RGC axons lack DV ordering along the LM tectal axis, but directionally extend interstitial branches that establish retinotopically ordered arbors. Recent studies show that ephrin-B1 acts as an attractant in DV mapping and in controlling directional branch extension. Modeling indicates that proper DV mapping requires that this attractant activity cooperates with a repellent activity in a gradient that mimics ephrin-B1. We show that ectopic domains of high, graded ephrin-B1 expression created by retroviral transfection repel interstitial branches of RGC axons and redirect their extension along the LM tectal axis, away from their proper termination zones (TZs). In contrast, the primary RGC axons are unaffected and extend through the ectopic domains of ephrin-B1 and arborize at the topographically correct site. However, when the location of a TZ is coincident with ectopic domains of ephrin-B1, the domains appear to inhibit arborization and shape the distribution of arbors. Our findings indicate that ephrin-B1 selectively controls, through either attraction or repulsion, the directional extension and arborization of interstitial branches extended by RGC axons arising from the same DV position: branches that arise from axons positioned lateral to the correct TZ are attracted up the gradient of ephrin-B1 and branches that arise from axons positioned medial to the same TZ are repelled down the ephrin-B1 gradient. Alternatively, EphB receptor signaling may act as a `ligand-density sensor' and titrate signaling pathways that promote branch extension toward an optimal ephrin-B1 concentration found at the TZ; branches located either medial or lateral to the TZ would encounter a gradient of increasingly favored attachment in the direction of the TZ.
Involvement of Oct3/4 in the enhancement of neuronal differentiation of ES cells in neurogenesis-inducing cultures
Authors: Shimozaki Koji , Nakashima Kinichi , Niwa Hitoshi , Taga Tetsuya
Published: April 2003

Oct3/4 plays a critical role in maintaining embryonic stem cell pluripotency. Regulatable transgene-mediated sustained Oct3/4 expression in ES cells cultured in serum-free LIF-deficient medium caused accelerated differentiation to neuroectoderm-like cells that expressed Sox2, Otx1 and Emx2 and subsequently differentiated into neurons. Neurogenesis of ES cells is promoted by SDIA (stromal cell-derived inducing activity), which accumulates on the PA6 stromal cell surface. Oct3/4 expression in ES cells was maintained by SDIA whereas without it expression was promptly downregulated. Suppression of Oct3/4 abolished neuronal differentiation even after stimulation by SDIA. In contrast, sustained upregulated Oct3/4 expression enhanced SDIA-mediated neurogenesis of ES cells. Therefore, Oct3/4 appears to promote neuroectoderm formation and subsequent neuronal differentiation from ES cells.
RNA binding and intramolecular interactions modulate the regulation of gene expression by nuclear factor 110
Authors: REICHMAN TREVOR W. , MATHEWS MICHAEL B.
Published: April 2003

Nuclear factor 110 (NF110) belongs to the nuclear factor 90 (NF90) family of double-stranded RNA (dsRNA) binding proteins that regulate gene expression at the transcriptional level in vertebrates. The proteins are identical at their N terminus, which functions as a negative regulatory region, but have distinct C termini as a result of alternate splicing. Maximal transcriptional activity of NF110 requires its C-terminal domain and a central domain that contains a nuclear localization signal and two dsRNA-binding motifs (dsRBMs). We find that dsRNA binding is reduced by RGG and GQSY motifs present in the C-terminal region. To directly evaluate the role of RNA binding in transactivation, we conducted site-directed mutagenesis to substitute conserved residues in one or both of the dsRBMs. The mutations reduced the ability of NF110 to stimulate gene expression to an extent that paralleled the mutants’ reduced ability to bind dsRNA. Full activity was restored when the dsRBM-containing region of NF110 was replaced with the RNA-binding region of the protein kinase PKR. Finally, NF110-mediated transactivation was inhibited by cotransfection of a plasmid encoding an artificial highly structured RNA. These data suggest that NF110 and its homologs are regulated by cis-acting domains present in some of the protein isoforms, and via interactions with RNAs that bind to their dsRBMs. We propose a model in which structured RNAs regulate gene expression by modulating transcription through interactions with members of the NF90 protein family.
The signal recognition particle binds to protein L23 at the peptide exit of the Escherichia coli ribosome
Authors: GU SHAN-QING , PESKE FRANK , WIEDEN HANS-JOACHIM , RODNINA MARINA V. , WINTERMEYER WOLFGANG
Published: April 2003

The signal recognition particle (SRP) from Escherichia coli, composed of Ffh protein and 4.5S RNA, mediates membrane targeting of translating ribosomes displaying a signal or signal-anchor sequence. SRP binds at the peptide exit of the large ribosomal subunit. Structural details of the interaction are not known. Here, the position of Ffh or SRP on the ribosome was probed by using site-specific UV-induced crosslinking by p-azidophenacyl bromide (AzP) attached to a number of cysteine residues engineered into surface positions of Ffh. Efficient crosslinking to vacant ribosomes took place from two positions (AzP17 and AzP25) in the N domain of Ffh, both with Ffh and SRP. Both AzP17 and AzP25 were predominantly crosslinked to ribosomal protein L23 that is located at the peptide exit of the 50S subunit. The SRP receptor, FtsY, did not change the crosslink pattern, whereas the presence of a nascent signal peptide on the ribosome resulted in a second crosslink between Ffh(AzP17) and protein L23, indicating that binding to the nascent signal peptide induced a slightly different arrangement of SRP on the ribosome. These results indicate a model of the topographical arrangement of SRP at the peptide exit of the 50S ribosomal subunit.
The effect of a single, temperature-sensitive mutation on global gene expression in Escherichia coli
Authors: LI YONG , COLE KYLE , ALTMAN SIDNEY
Published: April 2003

High-density DNA microarrays have been used to explore the genomic profiling of gene expression of a defective Escherichia coli strain with a temperature-sensitive mutation in the protein component of RNase P. A novel gene cluster was discovered in which two of the genes are known substrates of RNase P. The expression pattern of essential genes and gene discovery from intergenic regions, for which other new transcripts are found, are also discussed.
Linezolid Resistance since 2001: SENTRY Antimicrobial Surveillance Program
Authors: Mutnick Alan H , Enne Victoria , Jones Ronald N
Published: April 2003

BACKGROUND:

The oxazolidinone class of antimicrobials has demonstrated remarkable activity against gram-positive cocci. Linezolid has proven to be a first-line therapeutic option for vancomycin-resistant strains. Linezolid clinical trial results and subsequent published case reports cite rare resistance emerging in patients receiving prolonged therapy.

OBJECTIVE:

To report the initial linezolid-resistant organisms from cases obtained through the SENTRY Antimicrobial Surveillance Program, after screening >40 000 gram-positive cocci without resistance between 1998 and 2000.

METHODS:

During 2001–2002, 8 resistant strains (from 8 different patients) located in 6 states from 7 different participating SENTRY institutions in the US were identified among bloodstream, respiratory, skin and soft tissue, and urinary tract infection isolates of Enterococcus faecalis, Enterococcus faecium, Staphylococcus epidermidis, and Streptococcus oralis. Resistance was detected by reference broth microdilution methods and confirmed by identical results using Etest (AB BIODISK, Solna, Sweden) and the standardized disk diffusion method.

RESULTS:

Minimum inhibitory concentration (MIC) and disk diffusion tests showed elevated MICs (≥8 μg/mL) and small inhibitory zone diameters (≤15 mm) for all strains to both linezolid and the investigational oxazolidinone AZD2563. Vancomycin resistance was detected in 2 of the 8 linezolid-resistant strains. All enterococci and the viridans-group streptococcus ( S. oralis) strain showed resistance to erythromycin. E. faecium strains were resistant to penicillins, but susceptible to quinupristin/dalfopristin. Only 3 of the patients had previously received the drug.

CONCLUSIONS:

Linezolid resistance remains rare, with only 8 isolates among 9833 (0.08%) monitored isolates identified between January 1, 2001, and June 30, 2002. Resistance, however, was no longer limited to enterococci. Clinical laboratories should test linezolid more widely to detect emerging resistance, especially for patients receiving oxazolidinone therapy. Longitudinal surveillance programs are warranted to detect a trend in the development of resistance, determine the molecular mechanism of resistance, and recommend alternative therapies or epidemiologic interventions.
Possible Cefotaxime-Induced Stevens–Johnson Syndrome
Authors: Liberopoulos Evagelos N , Liamis George L , Elisaf Moses S
Published: April 2003

OBJECTIVE:

To report a case of possible cefotaxime-induced Stevens–Johnson syndrome (SJS).

CASE SUMMARY:

A 72-year-old woman with an upper urinary tract infection developed erosions and blisters on the skin and the mucous membranes, as well as fever and prostration, soon after the administration of cefotaxime. This presentation is consistent with the features of SJS. Resolution of the clinical manifestations was observed after discontinuation of the drug; all other drugs, infections, or immunologic disorders that could have caused this syndrome were carefully excluded. An objective causality assessment revealed that SJS was possibly associated with the use of cefotaxime.

DISCUSSION:

Although cephalosporins have been associated with an increased risk for SJS and cefotaxime has been suspected of being associated with SJS in a previous case–control study, this is the first full report for cefotaxime-related SJS in the literature. An immunologically mediated reaction may be the underlying mechanism.

CONCLUSIONS:

Although cefotaxime administration seems to be the underlying cause of the SJS observed in our patient, establishment of a definite causal relationship requires additional cases and supportive data.
Robust adaptive control for non‐linear systems in generalized output‐feedback canonical form
Authors: Krishnamurthy P. , Khorrami F.
Published: April 2003

Design of global robust adaptive output‐feedback dynamic compensators for stabilization and tracking of a class of systems that are globally diffeomorphic into systems in generalized output‐feedback canonical form is investigated. This form includes as special cases the standard output‐feedback canonical form and various other forms considered previously in the literature. Output‐dependent non‐linearities are allowed to enter both additively and multiplicatively. The system is allowed to contain unknown parameters multiplying output‐dependent non‐linearities and, also, unknown non‐linearities satisfying certain bounds. Under the assumption that a constant matrix can be found to achieve a certain property, it is shown that a reduced‐order observer and a backstepping controller can be designed to achieve practical stabilization of the tracking error. If this assumption is not satisfied, it is shown that the control objective can be achieved by introducing additional dynamics in the observer. Sufficient conditions under which asymptotic tracking and stabilization can be achieved are also given. This represents the first robust adaptive output‐feedback tracking results for this class of systems. Copyright © 2003 John Wiley & Sons, Ltd.
Long‐term survival in a patient with del(18)(q12.2q21.1)
Authors: Tinkle Brad T. , Christianson Carol A. , Schorry Elizabeth K. , Webb Thomas , Hopkin Robert J.
Published: April 2003

The 18q‐ syndrome is relatively common among cytogenetic abnormalities occurring in approximately 1 in 40,000 live births. However, interstitial deletions involving 18q12.2 to q21.1 are much less common. Only 15 cases have been reported in the literature. A phenotypic pattern is emerging of mild dysmorphic features, mental retardation, behavior abnormalities, and the lack of serious malformations. We present a 67‐year‐old woman with minor dysmorphic features, moderate mental retardation, hyperphagia, and del(18)(q12.2q21.1). This patient is presented for the natural history of this deletion syndrome as well as the behavioral phenotype. © 2003 Wiley‐Liss, Inc.
Different mutations in theNF1gene are associated with Neurofibromatosis–Noonan syndrome (NFNS)
Authors: Baralle Diana , Mattocks Chris , Kalidas Kamini , Elmslie Frances , Whittaker Joanne , Lees Melissa , Ragge Nicola , Patton Michael A. , Winter Robin M. , ffrench‐Constant Charles
Published: April 2003

The association of the Noonan phenotype with neurofibromatosis type 1 (NF1) was first noted by Allanson et al. [Am J Med Genet 1985;21:457–462.] and 30 further cases have subsequently been reported. It has been suggested that this phenotype is more common than previously appreciated, as Colley et al. [Clin Genet 1996;49:59–64.] examined 94 sequentially identified patients with NF1 from their genetic register and found Noonan features in 12. A 3‐bp deletion of exon 17 of theNF1neurofibromin gene was described in one family by Carey et al. [Proc Greenwood Genet Center 1997;17:52–53]. However, it remains unclear whether Neurofibromatosis–Noonan syndrome (NFNS) represents a form of NF1 (with mutations in theNF1neurofibromin gene) or a separate syndrome. We have used a new, rapid sequence analysis technique—comparative sequence analysis (CSA)—to examine theNF1gene in six patients with NFNS. None of the six patients had the previously identified mutation, nor did we observe other mutations within this exon. However, two other mutations were found: in exon 25, a 3‐bp deletion 4312 del GAA, and in exon 23‐2, a 2‐bp insertion 4095 ins TG. ThePTPN11gene, now known to cause over 50% of Noonan syndrome was also examined in four cases of NFNS, and no mutations were found. These results show that NFNS can in some cases result from different mutations in theNF1gene and therefore represents a variant form of NF1. © 2003 Wiley‐Liss, Inc.
High resolution mapping and mutation analyses of candidate genes in the urofacial syndrome (UFS) critical region
Authors: Wang Cong‐Yi , Davoodi‐Semiromi Abodoreza , Shi Jing‐Da , Yang Ping , Huang Yi‐Qun , Agundez Jose A. G. , Moran Jose M. , Ochoa Bernardo , Hawkins‐Lee Bobbilynn , She Jin‐Xiong
Published: April 2003

The urofacial (Ochoa) syndrome (UFS) characterized by congenital obstructive uropathy and abnormal facial expression is a rare disorder caused by a single recessive disease gene. Our previous studies using homozygosity mapping have located the UFS gene to a genomic interval of approximately 360 kb on chromosome 10q23‐10q24. In this study, we have constructed a genomic sequence map covering the entire UFS interval and narrowed the disease interval to a genomic region of 220 kb that harbor the newly identified ACDP1 gene in addition to part of the GOT1 gene which has already been excluded as a candidate for UFS. Extensive search for mutations in the coding region, the 5′ and 3′ untranslated regions, the promoter region, and the exon/intron junctions failed to identify a pathogenic mutation in UFS patients. Furthermore, our analyses indicated that the same gene on chromosome 10q is responsible for all UFS patients from multiple ethnic groups. © 2003 Wiley‐Liss, Inc.
Specific BACE1 genotypes provide additional risk for late‐onset alzheimer disease in APOE ε4 carriers
Authors: Gold Gabriel , Blouin Jean‐Louis , Herrmann François R. , Michon Agnès , Mulligan Reinhild , Duriaux Saïl Geneviève , Bouras Constantin , Giannakopoulos Panteleimon , Antonarakis Stylianos E.
Published: April 2003

Alzheimer disease (AD) is characterized neuropathologically by neurofibrillary tangles and senile plaques. A key component of plaques is Aβ, a polypeptide derived from Aβ‐precursor protein (APP) through proteolytic cleavage catalyzed by β and γ‐secretase. We hypothesized that sequence variation in genes BACE1 (on chromosome 11q23.3) and BACE2 (on chromosome 21q22.3), which encode two closely related proteases that seem to act as the APP β‐secretase, may represent a genetic risk factor for AD. We analyzed the frequencies of single nucleotide polymorphisms (SNPs) in BACE1 and BACE2 genes in a community‐based sample of 96 individuals with late‐onset AD and 170 controls selected randomly among residents of the same community. The genotype data in both study groups did not demonstrate any association between AD and BACE1 or BACE2. After stratification for APOE status, however, an association between a BACE1 polymorphism located within codon V262 and AD in APOE ε4 carriers was observed (P = 0.03). We conclude that sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; however, a combination of a specific BACE1 allele and APOE ε4 may increase the risk for Alzheimer disease over and above that attributed to APOE ε4 alone. © 2003 Wiley‐Liss, Inc.
5HTTLPR polymorphism in schizophrenic patients: Further support for association with violent suicide attempts
Authors: Bayle F.J. , Leroy S. , Gourion D. , Millet B. , Olié J.P. , Poirier M.F. , Krebs M.O.
Published: April 2003

Previous studies testing the functional polymorphism in the promoter of the serotonin‐transporter gene (5HTTLPR) in various psychiatric conditions have suggested that the association could be with an intermediate phenotype, impulsivity and/or violence rather than with a diagnosis. Schizophrenia is associated with a high risk of suicide, especially in patients with high impulsivity. We examined whether this polymorphism could be associated with violent suicide and/or impulsivity in schizophrenic patients. We genotyped the 5HTTLPR polymorphism in 185 unrelated schizophrenic patients from a French Caucasian population. The genotype frequencies significantly differed between patients who made violent suicide attempts and both, those who attempted suicide with a non‐violent method (P = 0.013) and those who never attempted suicide (P = 0.026). The genotypes containing the low activity “short” allele was significantly more frequent in violent suicide attempters (P = 0.007) than in non‐violent suicide attempters. No evidence was found for an association either with schizophrenia itself, when compared to gender and ethnically matched controls (n = 159) or with impulsivity, assessed using Barratt's Impulsivity Scale. Although replication studies are warranted, these results in schizophrenia further support the hypothesis that 5HTTLPR polymorphism is a risk factor for violent suicidal behavior. © 2003 Wiley‐Liss, Inc.
Genetic heterogeneity in a very large bipolar affective disorder pedigree from Quebec
Authors: Shink E. , Morissette J. , Barden N.
Published: April 2003

We previously reported a genome‐wide scan for bipolar affective disorder based on a multigenerational family sampled from a relatively homogeneous population derived from founding families that migrated to an isolated area of Quebec from the early 1830s onwards. For the genome scan, the pedigree was split into five branches to facilitate calculation and a second family was added to more specifically analyze chromosome 12 results. In the present study, we reanalyzed the undivided pedigree after genealogical links were reconstructed over ten generations to investigate a founder effect using an algorithm in the SIMWALK2 package. Our results do not lend support to the presence of a common haplotype shared among affected individuals. © 2003 Wiley‐Liss, Inc.
Severe myoclonus‐dystonia syndrome associated with a novel epsilon‐sarcoglycan gene truncating mutation
Authors: Maréchal Lucie , Raux Grégory , Dumanchin Cécile , Lefebvre Guillaume , Deslandre Emmanuelle , Girard Carole , Campion Dominique , Parain Dominique , Frebourg Thierry , Hannequin Didier
Published: April 2003

Myoclonus‐dystonia syndrome (MDS) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions, associated with psychiatric manifestations. MDS is usually considered as a benign disease. In most of the families, MDS is linked to chromosome 7q21 and mutations within epsilon‐sarcoglycan (SGCE) gene have been recently described. We report a MDS family with a severe and heterogeneous phenotype, including myoclonus with important functional impact and several psychiatric features, characterized by obsessive‐compulsive disorder, depression, and anxiety. This phenotype was shown to be associated with a novel truncating mutation located within exon 4 of SGCE. © 2003 Wiley‐Liss, Inc.
Genome scan of a second wave of NIMH genetics initiative bipolar pedigrees: chromosomes 2, 11, 13, 14, and X
Authors: Zandi Peter P. , Willour Virginia L. , Huo Yuqing , Chellis Jennifer , Potash James B. , MacKinnon Dean F. , Simpson Sylvia G. , McMahon Francis J. , Gershon Elliot , Reich Theodore , Foroud Tatiana , Nurnberger John , DePaulo J. Raymond , McInnis Melvin G.
Published: April 2003

As part of the on‐going NIMH Genetics Initiative on Bipolar Disorder, we have ascertained 153 multiplex bipolar pedigrees and genotyped them in two waves. We report here the genome scan results for chromosomes 2, 11, 13, 14, and X in the second wave of 56 families. A total of 354 individuals were genotyped and included in the current analyses, including 5 with schizoaffective/bipolar (SA/BP), 139 with bipolar I disorder (BPI), 41 with bipolar II disorder (BPII), and 43 with recurrent unipolar depression (RUP). Linkage analyses were carried out with multi‐point parametric and non‐parametric affected relative pair methods using three different definitions of the affected phenotype: (model 1) SA/BP and BPI; (model 2) SA/BP, BPI, and BPII; and (model 3) SA/BP, BPI, BPII, and RUP. The best findings were on 11p15.5 (NPL = 2.96, P = 0.002) and Xp11.3 (NPL = 2.19, P = 0.01). These findings did not reach conventional criteria for significance, but they were located near regions that have been identified in previous genetic studies of bipolar disorder. The relatively modest but consistent findings across studies may suggest that these loci harbor susceptibility genes of modest effect in a subset of families. Large samples such as that being collected by the NIMH Initiative will be necessary to examine the heterogeneity and identify these susceptibility genes. © 2003 Wiley‐Liss, Inc.
Depression in Alzheimer's disease: The effect of serotonin receptor gene variation
Authors: Holmes Clive , Arranz Maria , Collier David , Powell John , Lovestone Simon
Published: April 2003

This study investigated possible associations between selected polymorphisms in the serotonin receptor genes, 5‐HT2A and 5‐HT2C, with the presence of co‐morbid depressive illness at baseline in a community based cohort of 158 patients with late onset patients with Alzheimer's disease (AD). An association was found between the presence of major depressive illness at baseline and both the 5‐HT2A and 5‐HT2C polymorphisms. Specifically, homozygous carriers of the 5‐HT2A C102 allele were five times more likely to have major depressive illness than heterozygotes. In addition, homozygous or hemizygous carriers of the 5‐HT2C Ser allele were 12 times more likely to have major depressive illness than homozygous or hemizygous carriers of the 5‐HT2C Cys allele. © 2003 Wiley‐Liss, Inc.
Apolipoprotein E in schizophrenia: A French association study and meta‐analysis
Authors: Schürhoff Franck , Krebs Marie‐Odile , Szöke Andrei , Loze Jean‐Yves , Goldberger Céline , Quignon Valérie , Tignol Jean , Rouillon Frédéric , Laplanche Jean‐Louis , Leboyer Marion
Published: April 2003

Schizophrenic disorders are complex genetic disorders that may involve multiple genes of small effect. Apolipoprotein E (ApoE) gene variants are associated with alterations in brain function and an increased risk of Alzheimer's disease (AD). However, conflicting results have been reported in schizophrenia. We compared the ApoE genotypes of 114 French Caucasian schizophrenic patients and 91 normal controls. No differences in ApoE allele or genotype frequencies were observed between the two groups. However, we observed a possible association between male schizophrenic patients and the ApoE ε2ε3 genotype. In addition, a meta‐analysis of all published case‐control studies on ApoE and schizophrenia did not support a major role for ApoE gene variants in schizophrenia as a whole. However, ApoE may be associated with particular forms of schizophrenia. © 2003 Wiley‐Liss, Inc.
Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia
Authors: Mancama D. , Arranz MJ. , Landau S. , Kerwin R.
Published: April 2003

The involvement of specific pathways mediated through muscarinic receptor activity has been widely implicated in schizophrenia. Extensive pharmacological evidence supports the systems role in mediating antipsychotic drug efficacy, while mounting physiological evidence demonstrates the presence of significant alterations to normal muscarinic receptor integrity in the disorder. The mechanisms that facilitate the systems involvement and their magnitude, however, remain poorly understood. We have proposed that alterations to normal muscarinic receptor expression exist in schizophrenia, and that these significantly influence the physiological changes often reported for the system amongst patients. In this study, we investigate this potential, and have selected to examine the muscarinic 1 receptor, which constitutes a major target for antipsychotic action and plays a conspicuous role in those regions central to the disorders pathophysiology. Using relative gene quantification, we measured post‐mortem levels of steady‐state cortical muscarinic 1 receptor cDNA in patients (N = 20) and unaffected controls (N = 20), and examined group differences in expression levels. Commensurate with our hypothesis, we observed significant reductions in muscarinic 1 receptor cDNA in our patient sample (F(1,37) = 4.73, P = 0.036) and have estimated this to constitute a 28% decrease compared to the control subjects (95% CI from 2 to 47%). These results provide evidence in support of altered muscarinic 1 receptor expression in schizophrenia, though further work is needed to corroborate these findings. © 2003 Wiley‐Liss, Inc.
Nanotechnologie mit weichen Materialien
Authors: Hamley I. W.
Published: April 2003

Die Natur nutzt die Selbstorganisation weicher Materialien auf vielfache Weise, um Zellmembranen, Biopolymerfasern oder Viren aufzubauen. Auch der Mensch ist seit kurzem in der Lage, Materialien im Nanomaßstab zu entwickeln, entweder durch Steuerung auf atomarer oder molekularer Ebene (Top‐Down) oder durch Selbstorganisation (Bottom‐Up). Die Selbstorganisation weicher Materialien kann genutzt werden, um vielfältige Nanostrukturen für die verschiedensten Anwendungen herzustellen. Die Vielfalt der Strukturen erklärt sich aus den schwachen Ordnungen, die wiederum auf nichtkovalenten Wechselwirkungen beruhen. Damit kommt der thermischen Energie eine besondere Bedeutung zu, da sie Übergänge zwischen Phasen mit unterschiedlichen Ordnungen ermöglicht. Die Stärken der Selbstorganisation lassen sich für die Herstellung von Nanopartikeln und ‐strukturen, der Entwicklung von Nanomotoren, der Nutzung der Biomineralisation bis hin zur Entwicklung funktionalisierter Übertragungsvektoren nutzen.
A Comparison of Procedures for Adaptive Choice of Location Tests in Flexible Two‐Stage Designs
Authors: Friede Tim , Kieser Meinhard , Neuhäuser Markus , Büning Herbert
Published: April 2003

Although linear rank statistics for the two‐sample problem are distribution free tests, their power depends on the distribution of the data. In the planning phase of an experiment, researchers are often uncertain about the shape of this distribution and so the choice of test statistic for the analysis and the determination of the required sample size are based on vague information. Adaptive designs with interim analysis can potentially overcome both problems. And in particular, adaptive tests based on a selector statistic are a solution to the first. We investigate whether adaptive tests can be usefully implemented in flexible two‐stage designs to gain power. In a simulation study, we compare several methods for choosing a test statistic for the second stage of an adaptive design based on interim data with the procedure that applies adaptive tests in both stages. We find that the latter is a sensible approach that leads to the best results in most situations considered here. The different methods are illustrated using a clinical trial example.