bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Saitohin gene involved in neurodegenerative diseases?
Authors: Verpillat Patrice , Ricard Sylvain , Hannequin Didier , Dubois Bruno , Bou Jacqueline , Camuzat Agnès , Pradier Laurent , Frebourg Thierry , Brice Alexis , Clerget‐Darpoux Françoise , Deleuze Jean‐François , Campion Dominique
Published: December 2002

Recently, a single nucleotide polymorphism that results in an amino acid change (Q7R) was identified in a previously undescribed gene, named saitohin, nested within the tau gene. We analyzed the distribution of this polymorphism in 499 patients with Alzheimer's disease, 91 patients with frontotemporal dementia, and 402 controls. This polymorphism was in complete disequilibrium with the well‐defined extended tau haplotype. We failed to replicate the association between the RR genotype and late‐onset Alzheimer's disease, but we found a trend toward an association between the QQ genotype and frontotemporal dementia. Thus, the saitohin Q allele, which is a novel determinant of the tau H1 haplotypes, might represent a causative factor involved in the determinism of several tauopathies.
Rat forebrain neurogenesis and striatal neuron replacement after focal stroke
Authors: Parent Jack M. , Vexler Zinaida S. , Gong Chao , Derugin Nikita , Ferriero Donna M.
Published: December 2002

The persistence of neurogenesis in the forebrain subventricular zone (SVZ) of adult mammals suggests that the mature brain maintains the potential for neuronal replacement after injury. We examined whether focal ischemic injury in adult rat would increase SVZ neurogenesis and direct migration and neuronal differentiation of endogenous precursors in damaged regions. Focal stroke was induced in adult rats by 90‐minute right middle cerebral artery occlusion (tMCAO). Cell proliferation and neurogenesis were assessed with bromodeoxyuridine (BrdU) labeling and immunostaining for cell type‐specific markers. Brains examined 10–21 days after stroke showed markedly increased SVZ neurogenesis and chains of neuroblasts extending from the SVZ to the peri‐infarct striatum. Many BrdU‐labeled cells persisted in the striatum and cortex adjacent to infarcts, but at 35 days after tMCAO only BrdU‐labeled cells in the neostriatum expressed neuronal markers. Newly generated cells in the injured neostriatum expressed markers of medium spiny neurons, which characterize most neostriatal neurons lost after tMCAO. These findings indicate that focal ischemic injury increases SVZ neurogenesis and directs neuroblast migration to sites of damage. Moreover, neuroblasts in the injured neostriatum appear to differentiate into a region‐appropriate phenotype, which suggests that the mature brain is capable of replacing some neurons lost after ischemic injury.
Analysis of pathways mediating preserved vision after striate cortex lesions
Authors: Schoenfeld Mircea Ariel , Noesselt Toemme , Poggel Dorothe , Tempelmann Claus , Hopf Jens‐Max , Woldorff Martin G. , Heinze Hans‐Jochen , Hillyard Steven A.
Published: December 2002

This study investigated the neural substrates of preserved visual functioning in a patient with homonymous hemianopsia and Riddoch syndrome after a posterior cerebral artery stroke affecting the primary visual cortex (area V1). The limited visual abilities of this patient included above‐chance verbal reports of movement and color change as well as discrimination of movement direction in the hemianopic field. Functional magnetic resonance imaging showed that motion and color‐change stimuli presented to the hemianopic field produced activation in several extrastriate areas of the lesioned hemisphere that were defined using retinotopic mapping. Magnetoencephalographic recordings indicated that evoked activity occurred earlier in the higher‐tier visual areas V4/V8 and V5 than in the lower‐tier areas V2/V3 adjacent to the lesion. In addition, the functional magnetic resonance imaging analysis showed an increased functional connectivity between areas V4/V8 and V5 of the lesioned hemisphere in comparison with the same areas in the intact hemisphere during the presentation of color changes. These results suggest that visual perception after the V1 lesion in Riddoch syndrome is mediated by subcortical pathways that bypass V1 and project first to higher‐tier visual areas V5 and V4/V8 and subsequently to lower‐tier areas V2/V3.
Clinical and subclinical dopaminergic dysfunction in PARK6‐linked parkinsonism: An 18F‐dopa PET study
Authors: Khan Naheed L. , Valente Enza Maria , Bentivoglio Anna Rita , Wood Nicholas W. , Albanese Alberto , Brooks David J. , Piccini Paola
Published: December 2002

PARK6, a locus for early‐onset recessive parkinsonism, has been causally implicated in nine unrelated families from four different countries. The gene is still unidentified and hence the importance of PARK6 as a cause of Parkinson's disease is unknown. To date, no pathology or functional imaging studies are available on PARK6‐linked parkinsonism. We have used 18F‐dopa positron emission tomography to study four patients who are homozygous and three asymptomatic relatives who are heterozygous for PARK6. The clinically affected PARK6 subjects had a similar 85% reduction in posterior dorsal putamen 18F‐dopa uptake to a group of idiopathic Parkinson's disease patients matched for clinical disease severity and duration but showed significantly greater involvement of head of caudate and anterior putamen. The group of asymptomatic PARK6 carriers showed a significant mean 20 to 30% reduction in caudate and putamen 18F‐dopa uptake in comparison with controls, individual values falling toward the bottom of the normal range. Our results indicate that PARK6 pathology results in a more uniform loss of striatal dopamine terminal function than Parkinson's disease. The subclinical loss of striatal dopamine storage capacity found in the PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect.
Geophysical Prospection Survey of an Ancient Amphorae Workshop at Tsoukalia, Alonnisos (Greece)
Authors: Sarris A. , Athanassopoulou E. , Doulgeri‐Intzessiloglou A. , Skafida Eu. , Weymouth J.
Published: December 2002

At Tsoukalia, Alonnisos, there are substantial remains of a fourth century BC transport amphora production site, consisting of dense surface scatters of ceramics and kiln debris. Typological studies have shown that Tsoukalia, together with other major coastal amphora workshop centres in the area of Sporades islands, participated in a trade network extending up to the Black Sea. The archaeological investigations in the area of the workshop, initiated in 1999, included surface survey, ethnographical studies, topographic mapping, geomorphological studies and geophysical survey. Geophysical techniques included magnetic (both fluxgate gradiometer and caesium gradiometer) and electromagnetic techniques and the application of ground‐penetrating radar. Geophysical prospection was used to locate areas of specific archaeological interest and map the subsurface architectural remains of the site, enhancing the reconstruction of the diachronic land use of the site and the wider area of interest and contributing to the further understanding of the economic patterns of ancient Ikos. Copyright © 2002 John Wiley & Sons, Ltd.
A case study in the analysis of patterns of aerial reconnaissance in a lowland area of southwest Scotland
Authors: Cowley D. C.
Published: December 2002

Analysis of aspects of an ongoing programme of aerial reconnaissance, looking for archaeological sites revealed as cropmarks, in a lowland part of southwest Scotland has identified biases in the survey. Areas of known potential tend to be targeted at the expense of less rewarding ground, contributing to an imbalance in the known distributions of sites created by regional variations in land‐use patterns. A relationship between areas with a high density of sites, in a year of exceptional cropmark formation, and a high incidence of sites that have not been adequately recorded also can be identified. The ongoing assessment of survey data is a key factor in offsetting the impact of such biases in the longer term, recognizing the active role of survey methods in data creation and the importance of understanding the biases inherent in data. Copyright © Crown Copyright 2002. Recorded with the permission of the controller of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Perceived social support from significant others, family and friends and several socio‐demographic characteristics
Authors: Prezza Miretta , Giuseppina Pacilli Maria
Published: December 2002

The first aim was to explore the relationship between socio‐demographic characteristics and perceived support from significant others, family and friends. Zimet, Dahlem, Zimet, and Farley's Multidimensional Scale of Perceived Social Support (MSPSS) (Journal of Personality Assessment, 52, 1988, 30–41) was administered to 418 males and 623 females between 18 and 77 years of age. The results indicate that family support is higher in males, and the support of friends decreases with age as does the support of significant others. Significant interactions also emerged between gender and age and between gender and marital status. No differences were found for educational level. The second aim was to discover which persons are identified as ‘special persons’ on the items of the ‘Significant others’ sub‐scale of the MSPSS. Copyright © 2002 John Wiley & Sons, Ltd.
Reduction in vascular access site bleeding in sequential abciximab coronary intervention trials
Authors: Blankenship James C. , Balog Craig , Sapp Shelly K. , Califf Robert M. , Lincoff A. Michael , Tcheng James E. , Topol Eric J.
Published: December 2002

We analyzed vascular access site bleeding from the EPIC, EPILOG, and EPISTENT trials to quantify the decrease in vascular bleeding complications in these three trials, especially those attributable to abciximab. The incidence of combined major and minor vascular access site bleeding in nonabciximab (heparin plus placebo) patients progressively decreased from EPIC (8.2%) to EPILOG (2.9%) to EPISTENT (1.7%; P < 0.001). Combined major and minor vascular access site bleeding in abciximab (heparin plus abciximab) patients decreased from EPIC (20%) to EPILOG (5.8%) to EPISTENT (2.2%; P < 0.001). There were more major vascular access site bleeds with abciximab compared to placebo in EPIC (odds ration 3.2; P < 0.001) but not in EPILOG or EPISTENT. Modified abciximab and heparin dosing and improved vascular access site management strategies have decreased the risk of vascular access bleeding during coronary intervention and have essentially eliminated the excess access site bleeding associated with abciximab. Cathet Cardiovasc Intervent 2002;57:476–483. © 2002 Wiley‐Liss, Inc.
Delayed appearance of coronary artery perforation following cutting balloon angioplasty
Authors: Maruo Takeshi , Yasuda Satoshi , Miyazaki Shunichi
Published: December 2002

Coronary artery perforation is a potential complication of percutaneous coronary intervention (PCI). It usually develops immediately following PCI, particularly when an atheroablate device is used. We report a case in which coronary artery perforation developed 4 days after PCI with a nondebulking device, a cutting balloon catheter. Cathet Cardiovasc Intervent 2002;57:529–531. © 2002 Wiley‐Liss, Inc.
Identifying the course of an anomalous left coronary artery using contrast‐enhanced electron beam tomography and three‐dimensional reconstruction
Authors: Sevrukov Alexander , Aker Nidal , Sullivan Christopher , Jelnin Vladimir , Candipan Robert C.
Published: December 2002

Coronary anomalies are a rare but recognized cause of myocardial ischemia and sudden death. Until recently, invasive coronary arteriography was the diagnostic method of choice. However, contrast‐enhanced electron beam tomography has the advantage of three‐dimensional visualization of anomalous coronary arteries. We describe a case of anomalous origin of the left coronary artery. Cathet Cardiovasc Intervent 2002;57:532–536. © 2002 Wiley‐Liss, Inc.
Efficacy and feasibility of helixcision for debulking neointimal hyperplasia for in‐stent restenosis
Authors: Nakamura Mamoo , Fitzgerald Peter J. , Ikeno Fumiaki , Honda Yasuhiro , Sousa J. Eduardo , Abizaid Alexandre , de Brito Fábio S. , Tofte Arne , Grube Eberhard , Patterson Greg R. , Yock Paul G. , Yeung Alan C. , Carter Andrew J.
Published: December 2002

The Helixcision system is a novel 6 Fr–compatible catheter designed to debulk tissue for in‐stent restenosis lesions. The purpose of this study was to determine the efficacy and feasibility of this new system for removing neointimal hyperplasia. A total of 32 in‐stent restenosis lesions in 32 patients were treated with helixcision followed by balloon angioplasty. Debulking efficacy was assessed with serial baseline intravascular ultrasound (IVUS) in a subset of 18 lesions. To investigate longitudinal efficacy, 3D analysis was also performed in 12 lesions with automated pullback to calculate average cross‐sectional areas across the stent. Prior to procedure, the angiographic reference diameter was 2.60 ± 0.46 mm. Immediately after procedure, minimum lumen diameter improved from 0.84 ± 0.33 to 2.19 ± 0.41 mm (P < 0.0001). IVUS showed a significant reduction of intimal area (IA) after helixcision (from 4.95 ± 2.04 to 2.88 ± 1.48 mm2; P < 0.001). Adjunctive balloon angioplasty further improved lumen area (LA) mainly by stent expansion rather than IA reduction at the site of minimum lumen area. The degrees of IA reduction and LA improvement were closely similar in volumetric analysis. Thirty‐day and 6‐month clinical follow‐up were available in 97% (n = 31) and 72% (n = 23) of the enrolled patients, respectively. At 30‐day follow‐up, no major adverse cardiac event was reported except for periprocedural CK elevation in two patients (6%). Target legion revascularization within 6 months was performed in six patients (26%). Preliminary results of helixcision indicate that this system is safe and feasible for the treatment of in‐stent restenosis. The concordant results between 2D and 3D IVUS analyses suggest that this unique technology can achieve uniform longitudinal debulking throughout the stent. The long‐term outcomes appeared to be favorable, considering the relatively diffuse lesion morphology. Cathet Cardiovasc Intervent 2002;57:460–466. © 2002 Wiley‐Liss, Inc.
Closure of secundum atrial septal defects with the amplatzer septal occluder device: Techniques and problems
Authors: Harper Richard W. , Mottram Philip M. , McGaw David J.
Published: December 2002

Percutaneous transvenous closure of atrial septal defects (ASDs) has become feasible in recent years, as later‐generation devices have largely overcome initial difficulties in device deployment and complication rates. The Amplatzer septal occluder (ASO) is one such device that we have used extensively and is, in our opinion, the most versatile and practical to use. It is capable of closing defects up to 40 mm in diameter via a relatively low‐profile delivery sheath. More importantly, the ASO may be easily withdrawn into the sheath after deployment but prior to release, which is essential in safely closing difficult defects where successful positioning on the initial deployment is not guaranteed. In this article based on our experience, review of the literature, and communications with other operators, we describe the various problems encountered in closing atrial septal defects and make suggestions as to the best way of overcoming these difficulties. Cathet Cardiovasc Intervent 2002;57:508–524. © 2002 Wiley‐Liss, Inc.
Right coronary artery arising from the pulmonary trunk in a 63‐year‐old man
Authors: Vijitbenjaronk Prasert , Glancy D. Luke , Ferguson T. Bruce , Tan Chun W. , Helmcke Frederick R.
Published: December 2002

Unlike anomalous origin of the left coronary artery (CA) from the pulmonary trunk (PT), right CA from the PT, a rare congenital malformation, may present in adulthood. We herein describe a man with anomalous origin of the right CA from the PT who presented with angina and syncope at age 63. Cathet Cardiovasc Intervent 2002;57:545–547. © 2002 Wiley‐Liss, Inc.
Interventional treatment of giant pseudoaneurysm with subsequent decompression of internal mammaria bypass
Authors: Hinterseer Martin , Becker Alexander , Steinbigler Peter , Näbauer Michael , Boekstegers Peter
Published: December 2002

We present a case of a 38‐year‐old patient with angina after direct current (DC) cardioversion. The patient's medical history included documented coronary heart disease with interventional treatment of the LAD and RCA followed by emergency CABG 6 months ago. On recent admission, the coronary angiography revealed a giant pseudoaneurysm of the left descending coronary artery complicated by compression of LIMA. The pseudoaneurysm was successfully treated with three stent grafts. Cathet Cardiovasc Intervent 2002;57:525–528. © 2002 Wiley‐Liss, Inc.
Intracoronary verapamil for reversal of no‐reflow during coronary angioplasty for acute myocardial infarction
Authors: Werner Gerald S. , Lang Klaus , Kuehnert Helmuth , Figulla Hans R.
Published: December 2002

No‐reflow is a frequent observation during direct PTCA for acute myocardial infarction (AMI) and associated with a poor clinical outcome. This study assesses the value of verapamil for reversal of no‐reflow during PTCA for AMI. In a consecutive series of 212 direct or rescue PTCAs for AMI, a TIMI flow grade < 3 was observed in 23 patients (10.8%). Ten of these patients had received GP IIb/IIIa antagonists before PTCA. Seven patients with AMI and TIMI grade 3 flow served as controls. All lesions were treated by stents. In 18 patients with systolic blood pressure > 90 mm Hg, nitroglycerine (0.1 mg i.c.) was given. Verapamil (1 mg over 2 min) was given via an infusion catheter distal to the angioplasty site. Before and after nitroglycerine, after verapamil, and 15 min later coronary flow was assessed by the TIMI frame count method (TFC). Nitroglycerine had no effect on TFC. Verapamil reduced TFC from 56 ± 9 frames to 24 ± 4 (P < 0.001). In controls, TFC did not change significantly. The TIMI flow grade was restored to TIMI flow grade 3 in 65%. In two of seven right coronary and one of three circumflex arteries, intermittent AV block II occurred during verapamil injection, which disappeared after atropine. No‐reflow after PTCA for AMI can be reversed by intracoronary verapamil. This supports the hypothesis that no‐reflow is caused by acute microvascular dysfunction probably because of a disorder in calcium homeostasis or microvascular spasm. Cathet Cardiovasc Intervent 2002;57:444–451. © 2002 Wiley‐Liss, Inc.
Structural and functional asymmetry in the normal and epileptic rat dentate gyrus
Authors: Scharfman Helen E. , Sollas Anne L. , Smith Karen L. , Jackson Meyer B. , Goodman Jeffrey H.
Published: December 2002

The rat dentate gyrus is usually described as relatively homogeneous. Here, we present anatomic and physiological data which demonstrate that there are striking differences between the supra‐ and infrapyramidal blades after status epilepticus and recurrent seizures. These differences appear to be an accentuation of a subtle asymmetry present in normal rats. In both pilocarpine and kainic acid models, there was greater mossy fiber sprouting in the infrapyramidal blade. This occurred primarily in the middle third of the hippocampus. Asymmetric sprouting was evident both with Timm stain as well as antisera to brain‐derived neurotrophic factor (BDNF) or neuropeptide Y (NPY). In addition, surviving NPY‐immunoreactive hilar neurons were distributed preferentially in the suprapyramidal region of the hilus. Extracellular recordings from infrapyramidal sites in hippocampal slices of pilocarpine‐treated rats showed larger population spikes and weaker paired‐pulse inhibition in response to perforant path stimulation relative to suprapyramidal recordings. A single stimulus could evoke burst discharges in infrapyramidal granule cells but not suprapyramidal blade neurons. BDNF exposure led to spontaneous epileptiform discharges that were larger in amplitude and longer lasting in the infrapyramidal blade. Stimulation of the infrapyramidal molecular layer evoked larger responses in area CA3 than suprapyramidal stimulation. In slices from the temporal pole, in which anatomic evidence of asymmetry waned, there was little evidence of physiological asymmetry either. Of interest, some normal rats also showed signs of greater evoked responses in the infrapyramidal blade, and this could be detected with both microelectrode recording and optical imaging techniques. Although there were no signs of hyperexcitability in normal rats, the data suggest that there is some asymmetry in the normal dentate gyrus and this asymmetry is enhanced by seizures. Taken together, the results suggest that supra‐ and infrapyramidal blades of the dentate gyrus could have different circuit functions and that the infrapyramidal blade may play a greater role in activating the hippocampus. J. Comp. Neurol. 454:424–439, 2002. © 2002 Wiley‐Liss, Inc.
Neuroanatomy of the mormyrid electromotor control system
Authors: Carlson Bruce A.
Published: December 2002

Mormyrid fish produce a diverse range of electric signals that are under the control of a central electromotor network. The anatomical organization of this network was delineated by injecting biotinylated compounds into neurophysiologically identified nuclei. Previous work using retrograde labeling with horseradish peroxidase indicated that the medullary command nucleus (CN) receives inputs from the precommand nucleus (PCN) at the mesencephalic–diencephalic border and the ventroposterior nucleus (VP) in the torus semicircularis. This study confirms these projections and identifies the dorsal posterior nucleus (DP) in the thalamus as an additional input to CN. DP and PCN form a bilateral column of cells extending ventrolaterally and caudally from the dorsal thalamus. The primary input to DP/PCN is from VP, which is identified as having two distinct subdivisions. A small group of large, multipolar cells along the ventral edge projects to DP/PCN and to CN, whereas a dorsal group of small, ovoid cells projects to DP/PCN but not to CN. VP receives input from the tectum mesencephali and the mesencephalic command‐associated nucleus (MCA). As in all vertebrates, the tectum mesencephali receives input from several sources and likely provides multimodal sensory input to the electromotor system. MCA is part of the electromotor corollary discharge pathway, and its projection to VP suggests a feedback loop. These results, combined with recent physiological studies and comparisons with other taxa, suggest that modifiable feedback to DP/PCN plays a critical role in electromotor control and that the different inputs to CN may each be responsible for generating distinct electric signals. J. Comp. Neurol. 454:440–455, 2002. © 2002 Wiley‐Liss, Inc.
Endomorphin‐1 and ‐2 immunoreactive cells in the hypothalamus are labeled by fluoro‐gold injections to the ventral tegmental area
Authors: Greenwell Thomas N. , Zangen Abraham , Martin‐Schild Sheryl , Wise Roy A. , Zadina James E.
Published: December 2002

Endomorphin‐1 and ‐2 (EM1, EM2) are endogenous opioids with high affinity and selectivity for the mu‐opioid receptor. Cells expressing EM‐like immunoreactivity (EM‐LI) are present in the hypothalamus, and fibers containing EM‐LI project to many brain regions, including the ventral tegmental area (VTA). The VTA is one of the most sensitive brain regions for the rewarding and locomotor effects of opioids. It contains mu‐opioid receptors, which are thought to mediate γ‐aminobutyric acid–dependent disinhibition of dopamine transmission to the nucleus accumbens. We investigated whether hypothalamic EM‐LI cells project to the VTA, where they could play a natural role in this circuitry. The retrograde tracer Fluoro‐Gold (FG) was microinjected into the anterior or posterior VTA in rats. Nine days later, colchicine was injected, and 24 hours later, the animals were perfused and processed for fluorescence immunocytochemistry. Numerous FG‐labeled cells were detected in the hypothalamus. Both EM1‐LI and EM2‐LI cells were present in the periventricular nucleus, between the dorsomedial and ventromedial hypothalamus and between the ventromedial and arcuate nuclei. Subpopulations of EM1‐LI and EM2‐LI cells were labeled by FG. Injections of FG to the anterior and posterior VTA were both effective in producing double‐labeled cells, and an anterior–posterior topographical organization between the VTA and hypothalamus was observed. The results support the idea that some endomorphin‐containing neurons in the hypothalamus project to the VTA, where they may modulate reward and locomotor circuitry. J. Comp. Neurol. 454:320–328, 2002. © 2002 Wiley‐Liss, Inc.
Strategies of emotion regulation in adolescents and young adults with substance dependence or eating disorders
Authors: Pierrehumbert Blaise , Bader Michel , Miljkovitch Raphaële , Mazet Philippe , Amar Michel , Halfon Olivier
Published: December 2002

Some authors argue that both substance dependence and eating disorders should be considered as dependent behaviours. Similarities and differences between these disorders, however, remain unclear. This study compares processes of emotion regulation in adolescents and young adults (15 to 25 years old) with substance dependence (SD) or eating disorders (ED). One hundred and thirteen SD, 50 ED and 86 non‐clinical subjects (NC), recruited in four French and Swiss locations, completed a self‐report questionnaire of emotion regulation strategies. This questionnaire addresses the subjects' relationships, concerning past and present family, and refers to Main's (1990) concept of primary strategy (balanced activation and deactivation of attachment behaviours), and of secondary strategies (hyperactivation or excessive deactivation of the attachment system). Participants were also questioned in structured interviews, about life events and DSM‐IV classification criteria. SD reported more adverse events than ED and NC. SD and ED reported using fewer primary strategies than NC, and SD had secondary strategies that were different from those of ED. Patients with eating disorders reported more hyperactivation, and SD reported more deactivation of the attachment system. It is hypothesized that while subjects with SD and ED have in common poorly regulated strategies, they differ in the way they process emotion or relationship‐related information. Copyright © 2002 John Wiley & Sons, Ltd.
Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment
Authors: Green Jeremy
Published: December 2002

The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal‐type signaling and the intersection of VegT and β‐catenin intracellular gradients reveal detailed steps in early long‐range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin‐Xbra‐Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct long‐range action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed. © 2002 Wiley‐Liss, Inc.
KATP channel activity is required for hatching in Xenopus embryos
Authors: Cheng Shing‐Ming , Chen Ivy , Levin Michael
Published: December 2002

A growing body of work suggests that the activity of ion channels and pumps is an important regulatory factor in embryonic development. We are beginning to identify functional roles for proteins suggested by a survey of expression of ion channel and pump genes in Xenopus and chick embryos (Rutenberg et al. [2002] Dev Dyn 225, this issue). Here, we report that the ATP‐sensitive K+ channel protein is present in the hatching gland of Xenopus embryos; moreover, we show that its activity is necessary for hatching in Xenopus. Pharmacologic inhibition of KATP channels not only specifically prevents the hatching process but also greatly reduces the endogenous expression of Connexin‐30 in the hatching gland. Based on recent work which showed that gap‐junctional communication mediated by Cx30 in the hatching gland was required for secretion of the hatching enzyme, we propose that KATP channel activity is upstream of Cx30 expression and represents a necessary endogenous step in the hatching of the Xenopus embryo. © 2002 Wiley‐Liss, Inc.
Xenopus bagpipe‐related gene, koza, may play a role in regulation of cell proliferation
Authors: Newman Craig S. , Krieg Paul A.
Published: December 2002

The homeobox gene koza is a new member of the vertebrate bagpipe‐related gene family. Embryonic expression of koza is observed at highest levels in the muscle layer of the somites and, during later development, is restricted to the lateral somitic cells, which correspond to slow twitch muscle tissue. Expression of koza is also observed in the myocardial layer of the heart and in the cement gland. In each of these tissues, koza transcription commences only after the expression of terminal differentiation markers. By injection of synthetic mRNA, we show that overexpression of koza leads to an apparent decrease in the number of cells in the somites. No reduction in cell number is observed when koza is present in neural tissues, suggesting that koza exhibits some tissue specificity in regulation of cell proliferation. Embryonic manipulations show that restriction of koza expression to the slow twitch muscle layer is independent of axial structures but is, at least partly, regulated by signals arising in ectodermal tissue. Finally, in Drosophila, bagpipe expression is regulated by the hedgehog signaling pathway. By using ectopic expression, we show that koza transcription is positively regulated by banded hedgehog. This result indicates that regulation of bagpipe expression by hedgehog signaling is evolutionarily conserved. © 2002 Wiley‐Liss, Inc.
Xenopus tropicalis transgenic lines and their use in the study of embryonic induction
Authors: Hirsch Nicolas , Zimmerman Lyle B. , Gray Jessica , Chae Jeiwook , Curran Kristen L. , Fisher Marilyn , Ogino Hajime , Grainger Robert M.
Published: December 2002

For over a century, amphibian embryos have been a source of significant insight into developmental mechanisms, including fundamental discoveries about the process of induction. The recently developed transgenesis for Xenopus offers new approaches to these poorly understood processes, particularly when undertaken in the quickly maturing species Xenopus tropicalis, which greatly facilitates establishment of permanent transgenic lines. Several X. tropicalis transgenic lines have now been generated, and experiments demonstrating the value of these lines to study induction in embryonic tissue recombinants and explants are presented here. A revised protocol for transgenesis in X. tropicalis resulting in a significant increase in the percentage of transgenic animals that reach adulthood is presented, as well as improvements in tadpole and froglet husbandry, which have facilitated the raising of large numbers of adults. Working transgenic populations have been rapidly expanded, and some transgenes have been bred to homozygosity. Established lines include those bearing the promoter regions of Pax‐6, Otx‐2, Rx, and EF1α coupled to fluorescent reporter genes. Multireporter lines combining, in a single animal, up to three gene promoters coupled to different fluorescent reporters have also been established. The value of X. tropicalis transgenic lines for the study of induction is demonstrated by showing activation of Pax‐6 by noggin treatment of Pax‐6/GFP transgenic animal caps, illustrating how reporter lines allow a rapid, in vivo assay for an inductive response. An experiment showing lens induction in gamma‐crystallin/GFP transgenic lens ectoderm when it is recombined with mouse optic vesicle demonstrates conservation of inducing signals from amphibians and mammals. It also shows how the warmer culture temperatures tolerated by X. tropicalis embryos can be used in assays of factors produced by mammalian cells and tissues. The many applications of transgenic reporter lines and other lines designed to target gene expression in particular tissues promise to bring significant new insights to the classic issues first defined in amphibian systems. © 2002 Wiley‐Liss, Inc.
Isolation and characterization of Xenopus Hey‐1: A downstream mediator of Notch signaling
Authors: Rones M.S. , Woda J. , Mercola M. , McLaughlin K.A.
Published: December 2002

Regulation of Notch signaling likely occurs, at least in part, at the level of basic helix‐loop‐helix (bHLH) transcription factors that function downstream of Suppressor of Hairless (Su(H)) in the Notch pathway. To begin to characterize modulation of Notch signaling during organogenesis, we examined the bHLH transcription factor, XHey‐1 (hairy related‐1) in early Xenopus laevis embryos. XHey‐1 is expressed in numerous tissues during early development including the somites, head, embryonic kidneys, and heart. Importantly, the expression of XHey‐1 was significantly altered in response to perturbation of Notch signaling by means of inducible constructs that served to either activate or suppress Notch signaling through Su(H) in a temporally controlled manner. © 2002 Wiley‐Liss, Inc.
Expression patterns of focal adhesion associated proteins in the developing retina
Authors: Li Ming , Sakaguchi Donald S.
Published: December 2002

Adhesive interactions between integrin receptors and the extracellular matrix (ECM) are intimately involved in regulating development of a variety of tissues within the organism. In the present study, we have investigated the relationships between β1 integrin receptors and focal adhesion associated proteins during eye development. We used specific antibodies to examine the distribution of β1 integrin ECM receptors and the cytoplasmic focal adhesion associated proteins, talin, vinculin, and paxillin in the developing Xenopus retina. Immunoblot analysis confirmed antibody specificity and indicated that β1 integrins, talin, vinculin, and paxillin were expressed in developing retina and in the retinal‐derived Xenopus XR1 glial cell line. Triple‐labeling immunocytochemistry revealed that talin, vinculin, paxillin, and phosphotyrosine proteins colocalized with β1 integrins at focal adhesions located at the termini of F‐actin filaments in XR1 cells. In the retina, these focal adhesion proteins exhibited developmentally regulated expression patterns during eye morphogenesis. In the embryonic retina, immunoreactivities for focal adhesion proteins were expressed in neuroepithelial cells, and immunoreactivity was especially strong at the interface between the optic vesicle and overlying ectoderm. At later stages, these proteins were expressed throughout all retinal layers with higher levels of expression observed in the plexiform layers, optic fiber layer, and in the region of the inner and outer limiting membrane. Strong immunoreactivities for β1 integrin, paxillin, and phosphotyrosine were expressed in the radially oriented Müller glial cells at later stages of development. These results suggest that focal adhesion‐associated proteins are involved in integrin‐mediated adhesion and signaling and are likely to be essential in regulating retinal morphogenesis. © 2002 Wiley‐Liss, Inc.
Formation of a full complement of cranial proprioceptors requires multiple neurotrophins
Authors: Fan Guoping , Copray Sjef , Huang Eric J. , Jones Kevin , Yan Qiao , Walro Jon , Jaenisch Rudolf , Kucera Jan
Published: December 2002

The original article to which this Erratum refers was published in Developmental Dynamics 218:359–370 Developmental Dynamics(2000) 218(2) 359–370

The corresponding author of this article regrets that information regarding the grant sponsors was inadvertently left out of the sponsor citations. The author would like to acknowledge that the published research was carried out at the Veterans Affairs Boston Healthcare System, 150 South Huntington Ave., Boston, MA 02130, and was supported by a Merit Review Award from the VA Medical Research Service.
Geophysical indicators of culturally emplaced soils and sediments
Authors: Dalan Rinita A. , Bevan Bruce W.
Published: December 2002

Archaeologists dealing with earthen forms must distinguish those constructed by humans from those with a natural origin. Geophysical techniques can help identify culturally loaded soils and sediments. We suggest that intrinsic changes in geophysical properties, due to cultural loading, can serve as fingerprints in determining whether a mound or other earthen form is natural or culturally constructed. Culturally emplaced soils might be identified through anomalous values in geophysical properties or through unusual spatial or stratigraphic complexity. The identification of this “lumpiness” in geophysical properties may involve geophysical techniques quite different from those employed in traditional archaeogeophysical surveys. Experiments at three prehistoric mound sites (the Cahokia Mounds State Historic Site, Effigy Mounds National Monument, and the Hopeton Earthwork) illustrate a number of these techniques including studies of the anisotropy (directionality) of geophysical properties, seismic Rayleigh (surface) waves, and magnetic susceptibility. © 2002 Wiley Periodicals, Inc.
A Mössbauer study of the color of Roman pottery from the Leptiminus archaeological site, Tunisia
Authors: Sherriff Barbara L. , McCammon Catherine , Stirling Lea
Published: December 2002

Variations in the color of pottery, white coatings on amphora, and dark edges on coarseware were produced by Roman potters at Leptiminus, Tunisia. The oxidation state and coordination of iron in different colored regions of the pottery was determined using Mössbauer spectroscopy. The basic red color of most pottery is due to hematite produced under oxidizing conditions in the kilns. The white surficial coloration, enhanced by treating the clay with salt water, is caused by the incorporation of iron into clinopyroxene instead of iron oxides. Recent pottery from Moknine, Tunisia, which was formed with clay mixed with either fresh or salt water, illustrates the effect of NaCl in producing the white coating. Black edges on Roman coarseware relate to high content of maghemite, probably produced under reducing conditions in the kiln. © 2002 Wiley Periodicals, Inc.
Cost data for individual patients included in clinical studies: no amount of statistical analysis can compensate for inadequate costing methods
Authors: Graves Nicholas , Walker Damian , Raine Rosalind , Hutchings Andrew , Roberts Jennifer A.
Published: December 2002

This work examines the quality of the cost methods used to derive patient level costs in 45 economic evaluations conducted alongside randomised controlled trials. The perspective of the cost analysis, the methods used to determine quantities and values of resources and how the cost data were reported are examined. The reported costing methods were found to be of poor quality, highlighting the need for greater rigour. Researchers to date appear more concerned with whether cost data have been subjected to the appropriate statistical analysis. For the results of clinical studies to be valid both cost methods and the methods used for the statistical analysis of cost data should be of a high quality. Copyright © 2002 John Wiley & Sons, Ltd.
A theoretical model of adolescent suicide and some evidence from US data
Authors: Mathur Vijay K. , Freeman Donald G.
Published: December 2002

Suicide rates for adolescents have doubled since 1970 and tripled since 1960, even as rates for other age groups have declined. Using a Becker‐type model of household production and consumption, we demonstrate conditions under which utility maximizing parents allocate time away from time‐intensive commodities like children's well‐being, and towards market work and less time‐intensive consumption commodities. This reallocation of time towards market work has mixed effects on children' mental health: higher money income tends to improve family and children's well‐being, but the loss of parental time has an opposite effect on children's mental health and increases the risk of adolescent suicide. Empirical evidence using state panel regressions of adolescent suicide rates on economic, social and demographic variables is consistent with predictions based on our model; our results indicate that the favorable effect of higher incomes has more than offset the negative effect of lost parental time. Copyright © 2002 John Wiley & Sons, Ltd.
A phase II trial of cisplatin and vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Espinosa Enrique , Zamora Pilar , Millá Alfredo , Morales Serafin , Molina Raquel , Mira M. , González Barón Manuel
Published: December 2002

Objective.

We assessed the response rate and the toxicity of cisplatin plus vinorelbine in patients with this condition.

Patients and Method.

Forty‐two patients were included. Therapy consisted of cisplatin, 100 mg/m2 on day 1, and vinorelbine, 25 mg/m2 on days 1 and 8, given every 21 days. Therapy was continued up to six courses or progressive disease.

Results.

One hundred fifty‐nine courses were given (median, three per patient). Dose reduction was applied in 13% of courses and 43% of patients. Grade 3 to 4 neutropenia appeared in 11% of courses and 35% of the patients. One patient died of febrile neutropenia. Ten percent of patients attained a complete response, and 23% attained a partial response (overall 33%, 95%CI 19%–47%). The median duration of response and median survival were 6 months. Twenty‐four percent of patients remain alive at 1 year.

Conclusions.

The combination of cisplatin and vinorelbine is moderately active in patients with recurrent or metastatic carcinomas of the head and neck and avoids the inconvenience of prolonged infusions of 5‐fluorouracil. © 2002 Wiley Periodicals, Inc. Head Neck 24: 1054–1059, 2002
The effects of a sedative antihistamine, d‐chlorpheniramine, on visuomotor spatial discrimination and regional brain activity as measured by positron emission tomography (PET)
Authors: Mochizuki Hideki , Tashiro Manabu , Tagawa Masaaki , Kano Michiko , Itoh Masatoshi , Okamura Nobuyuki , Watanabe Takehiko , Yanai Kazuhiko
Published: December 2002

Although most people taking antihistamines have experienced sedation and impaired performance, the neural correlates of these sedative properties are not well understood in man. Brain imaging can be used to demonstrate how regional brain activities are altered during such sedative effects. The aim of this study was to visualize the brain mechanism of impaired visuomotor spatial cognition with orally administered d‐chlorpheniramine, a first‐generation sedative antihistamine, using H215O and positron emission tomography (PET). Normal subjects were randomly assigned to two groups (chlorpheniramine and placebo) and performed a spatial discrimination task after the oral administration of 6 mg d‐chlorpheniramine or a placebo. The administration of d‐chlorpheniramine impaired visuomotor spatial discrimination and altered cortical and subcortical activity. Decreased and increased activities were observed in the right parietal cortex (BA 40) which is related to visuomotor spatial cognition and the posterior cingulate cortex which constitutes the attention system of the brain, respectively. In particular, the brain activities of BA 40 were negatively and positively correlated to those of bilateral caudate nuclei and the dorsolateral prefrontal cortex, respectively. These findings clearly suggest that the alteration in the cortical and subcortical activity contributes to impaired spatial cognition caused by treatment with d‐chlorpheniramine. Copyright © 2002 John Wiley & Sons, Ltd.
Dextro‐amphetamine increases phosphoinositol cycle activity in volunteers: an MRS study
Authors: Silverstone Peter H. , O'Donnell Tina , Ulrich Michele , Asghar Sheila , Hanstock Christopher C.
Published: December 2002

Aims

To help determine the effects of dextro‐amphetamine on the phosphoinositol cycle (PI‐cycle) in humans, 1H and 31P magnetic resonance spectroscopy (MRS) was utilized in 17 healthy volunteers. This was an open‐label study carried out before and after administration of 20 mg oral dextro‐amphetamine. Subjects also rated the subjective effects of dextro‐amphetamine administration using visual analog scales (VAS).

Major findings

Following dextro‐amphetamine administration there was a significant increase in the concentrations of both myo‐inositol and phosphomonoesters.

Conclusions

These findings are in keeping with suggestions that dextro‐amphetamine administration increases the activity of the phosphoinositol cycle, probably via an indirect release of dopamine and noradrenaline. These results are the first time that this has been confirmed in humans. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacotherapy of anxious disorders
Authors: Bourin Michel , Lambert Olivier
Published: December 2002

The present paper is a review of the treatment of anxious disorders by the current pharmaceutical medications; a short epidemiological survey is given for anxious disorders including: general anxiety disorder, panic disorder, obsessive compulsive disorder, social anxiety and post‐traumatic stress disorder. For all these disorders there are proposals of treatment built on literature data mainly on meta‐analysis as well on personal experience. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacotherapy of bipolar disorder: the role of atypical antipsychotics and experimental strategies
Authors: Malhi Gin S. , Berk Michael
Published: December 2002

Bipolar disorder, despite being a common and debilitating illness, has remarkably few pharmacological therapeutic options, the majority of which, with the exception of lithium, have been borrowed from other medical indications. Furthermore the quantity and quality of controlled clinical data are considerably smaller than in conditions of comparable severity and frequency. Not surprisingly, the clinical outcome of bipolar disorder is frequently suboptimal.

Fortunately there are a growing number of novel therapeutic options for its treatment such as atypical antipsychotics, calcium channel blockers and omega‐3 fatty acids. This paper summarizes some of the data regarding these ‘experimental’ therapeutic options, focusing principally on atypical antipsychotics as these are now widely prescribed in the management of bipolar disorder. Copyright © 2002 John Wiley & Sons, Ltd.