bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal of the direction of internal carotid artery blood flow by occlusion of the common and external carotid arteries in a swine model
Authors: Bates Mark C. , Dorros Gerald , Parodi Juan , Ohki Takao
Published: September 2003

In a swine model, blood flow direction [antegrade (+) and retrograde (−)] and velocity were defined within the common (CCA), internal (ICA), and external (ECA) carotid arteries during CCA occlusion with and without ECA occlusion and blood aspiration. In seven anesthetized swine, Doppler recordings of blood flow direction and velocity were performed in the CCA, ICA, and ECA, before and after vessel(s) occlusion, and after passively and actively induced reversal of blood flow direction. Baseline ICA and ECA blood flow direction and velocities were 92 ± 4 and 90 ± 3 cm/sec; and, with CCA occlusion, the ICA velocity decreased to 30 ± 2 cm/sec (P < 0.001). No flow (zero velocity) occurred with CCA and ECA occlusion. An artificial femoral arteriovenous fistula's continuous gradient passively reversed ICA blood flow direction (−), with the recorded blood's velocity (−24 ± 4 cm/sec) increasing with continuous active aspiration to −90 ± 6 cm/sec. Occlusion of the CCA occlusion alone was unable completely to halt ICA antegrade blood flow direction, while CCA and ECA occlusion completely stopped ICA antegrade flow. CCA and ECA occlusion, when coupled with an arteriovenous fistula arteriovenous and/or aspiration, resulted in ICA blood flow direction reversal, whose velocity could be actively augmented.Catheter Cardiovasc Interv 2003;60:270–275. ©2003Wiley‐Liss,Inc.
Initial experience with a new 8 French‐compatible directional atherectomy catheter: Immediate and mid‐term results
Authors: Orlic Dejan , Reimers Bernhard , Stankovic Goran , Corvaja Nicola , Chieffo Alaide , Airoldi Flavio , Spanos Vassilis , Favero Luca , Di Mario Carlo , Colombo Antonio
Published: September 2003

The purpose of this study was to evaluate the safety and efficacy of the new Fox Hollow atherectomy device (FHT) designed for more efficient and easier plaque removal. The FHT has short rigid section and low‐profile cutter mounted on a monorail catheter. The FHT catheter was utilized in 77 patients with 98 lesions. Mean reference vessel diameter was 2.75 ± 0.51 mm. Successful atherectomy with tissue retrieval was performed in 94 lesions (96%). Following atherectomy, mean diameter stenosis was reduced from 71.1% to 31.9% and further to 10.4% following adjunctive treatment. Angiographic complications were one coronary perforation and one adventitial staining, both successfully treated with prolong balloon inflation and stent implantation. Nine patients (11.7%) had in‐hospital non‐Q‐wave myocardial infarction (MI). One patient died (1.3%) for noncardiac reasons and one had MI (1.3%) at 6‐month follow‐up. Target lesion revascularization was required in 13 (13.8%) lesions and target vessel revascularization in 15 (20.3%) patients. There was target vessel failure in 17 (23.0%) patients. Plaque debulking with the FHT catheter can be performed safely and effectively in relatively small vessels and complex lesions located in mid‐distal artery segments with 6‐month clinical outcome similar to prior atherectomy devices. Catheter Cardiovasc Interv 2003;60:159–166. © 2003 Wiley‐Liss, Inc.
Sequential endovascular coil embolization for a traumatic cervical vertebral AV fistula
Authors: Hung Chung‐Lieh , Wu Yih‐Jer , Lin Chung‐Shu , Hou Charles Jia‐Yin
Published: September 2003

An arteriovenous (AV) fistula involving the cervical vertebral artery is rare. Iatrogenic injury from percutaneous puncture and penetrating wounds are the most common causes. Symptoms include tinnitus and the presence of a pulsatile mass with a thrill. Conservative treatment with coil embolization and preservation of the vertebral artery is an alternative to surgical intervention. We report a patient who developed an AV fistula involving the vertebral artery and internal jugular vein following surgical repair of a stab wound to the neck. The sequential endovascular coil embolism was performed with subsequent successful occlusion of fistula. No neurological deficit developed during or after intervention. This approach appears to be a safe method in the treatment of vertebral AV fistula.Catheter Cardiovasc Interv 2003;60:267–269. ©2003 Wiley‐Liss, Inc.
Arterial thrombosis for the interventional cardiologist: From adhesion molecules and coagulation factors to clinical therapeutics
Authors: Conde Ian D. , Kleiman Neal S.
Published: September 2003

Arterial thrombosis is the result of a complex and well‐orchestrated set of events where interactions between platelets and leukocytes are intertwined with enzymatic reactions of the coagulation system. Here, we present a contemporary panorama of arterial thrombosis and provide a framework the interventionalist can use to understand the current antithrombotic pharmacotherapies and recognize the role of therapies that have yet to be developed. We analyze thrombosis in the context of plaque rupture and vascular injury and describe the interactions between platelets and the subendothelium. We then discuss platelet‐leukocyte interactions, emphasizing the inflammatory nature of thrombosis and how this relates to vessel restenosis following angioplasty. The different reactions of the coagulation system are described not from an isolated perspective, but are integrated into the sequence of cell‐cell interactions that parallel them. Finally, we describe the mechanisms that terminate the thrombotic response. Catheter Cadiovasc Interv 2003;60:236–246. © 2003 Wiley‐Liss, Inc.
Study of antirestenosis with the BiodivYsio dexamethasone‐eluting stent (STRIDE): A first‐in‐human multicenter pilot trial
Authors: Liu Xiaoshun , Huang Yanming , Hanet Claude , Vandormael Michel , Legrand Victor , Dens Joseph , Vandenbossche Jean Luc , Missault Luc , Vrints Christiaan , De Scheerder Ivan
Published: September 2003

The aim of this multicenter pilot study was to evaluate the acute safety and efficacy of the dexamethasone‐eluting stent (0.5 μg/mm2 of stent) implanted in patients with de novo single‐vessel disease. This study included 71 patients, 42% of whom had unstable angina pectoris. An appropriately sized BiodivYsio Matrix Lo stent loaded with a total dexamethasone dose of 0.5 μg/mm2 of stent was used. Technical device success rate was 95%. Six‐month MACE occurred in two patients (3.3%). Binary restenosis rate was 13.3%. Late loss was 0.45. Late loss and percent diameter stenosis were lower in the unstable angina pectoris patients compared to the stable patients (0.32 ± 0.39 vs. 0.60 ± 0.55 mm, P < 0.07, and 26.86 ± 14 vs. 38.40 ± 16%, P < 0.02). This study demonstrated the feasibility and safety of the implantation of a dexamethasone‐eluting stent and its effect on in‐stent neointimal hyperplasia. Catheter Cardiovasc Interv 2003;60:172–178. © 2003 Wiley‐Liss, Inc.
Pacman sign during device closure of the patent foramen ovale
Authors: Meier Bernhard
Published: September 2003

The Pacman Sign during devise closure of the patent foramen ovale refers to the aspect of the device on fluoroscopy that should be achieved before release. In an orthograde view, the cranial halves of the left and right atrial disks should appear like open jaws biting into the thick septum secundum reminding of arcade game figure Pacman about to gobble up a dot. Catheter Cardiovasc Interv 2003;60:221–223. © 2003 Wiley‐Liss, Inc.
Distal protection in native coronary arteries during primary angioplasty in acute myocardial infarction: Single‐center experience
Authors: Orrego Pedro Silva , Delgado Anabella , Piccalò Giacomo , Salvadè Paolo , Bonacina Edgardo , Klugmann Silvio
Published: September 2003

Distal embolization of plaque or thrombotic debris is one of the mechanisms involved in the ischemia/reperfusion injury during primary percutaneous intervention for acute occlusion of a native coronary artery. We tested the clinical application of maximal antiplatelet therapy with abciximab combined with one of two different systems of mechanical distal protection: balloon occlusion and aspiration (PercuSurge) in 24 cases and a distal filter (FilterWire Ex) in 10 cases. Feasibility, technical limitations, and pitfalls are described. Catheter Cardiovasc Interv 2003;60:152–158. © 2003 Wiley‐Liss, Inc.
High‐speed rotational atherectomy and coronary stenting: QCA and QCU analysis
Authors: Whitbourn Robert J. , Sethi Rajiv , Pomerantsev Eugene V. , Fitzgerald Peter J.
Published: September 2003

To evaluate the acute effect of pretreatment with high‐speed rotational atherectomy (HSRA) on stent deployment (rotastenting), we studied 33 patients with rotastenting of 40 segments, 34 patients with 40 coronary segments treated with Palmaz‐Schatz stenting alone, and 34 patients with 40 segments treated with HSRA. The HSRA‐ and stent‐alone patient groups were selected retrospectively by matching the quantitative coronary angiography (QCA) reference diameter (D ref). QCA revealed similar baseline percent of stenosis (85.3% ± 12.4%), minimal luminal diameter (MLD), and D ref. The percent area expansion was calculated as a ratio between the minimal intrastent area and the reference area measured by intracoronary ultrasound. The rotastent group was characterized by more frequent calcification compared to HSRA and stent groups (67.5% vs. 20% and 12.5%; P < 0.01). Lesion length determined by QCA was longer both in the HSRA and the rotastent groups vs. the stent‐alone group (21.1 ± 12.3 and 20.9 ± 4.3 vs. 17.0 ± 7.7 mm; P < 0.05). In this small study, there was no difference demonstrated between final MLD in the rotastent and stent‐alone groups. However, a smaller MLD was achieved in the HSRA group (3.0 ± 0.7 vs. 3.1 ± 0.5 vs. 2.5 ± 0.7 mm, respectively; P < 0.01). The degree of stent expansion was higher in the rotastent group compared to the stent‐alone group (91.9% ± 4.4% vs. 79.7% ± 3.4%; P < 0.03) and the % residual area of plaque was less for the rotastent group than for the stent‐alone group (12.1% ± 13.2% vs. 21.1% ± 17.5%; P = 0.03). These data suggest that antecedent HSRA atheroma debulking using HSRA results in improved intravascular stent expansion and reduction in residual plaque, facilitating optimal stent deployment. Catheter Cardiovasc Interv 2003;60:167–171. © 2003 Wiley‐Liss, Inc.
Updated review of the global carotid artery stent registry
Authors: Wholey Michael H. , Al‐Mubarek Nadim , Wholey Mark H.
Published: September 2003

The purpose of this article was to review and update the current status of carotid artery stent placement in the world. Surveys of major interventional centers in Europe, North and South America, and Asia were initially completed in June 1997. Subsequent updates from these 24 centers in addition to 29 new centers have been obtained to bring up to date the information. The survey asked the various questions regarding the patients enrolled, procedure techniques, and results of carotid stenting, including complications and restenosis. The total number of endovascular carotid stent procedures that have been performed worldwide to date included 12,392 procedures involving 11,243 patients. There was a technical success of 98.9% with 12,254 carotid arteries treated. Complications that occurred during the carotid stent placement or within a 30‐day period following placement were recorded. Overall, there was transient ischemic attack rate of 3.07%, minor strokes of 2.14%, major strokes of 1.20%, and procedure‐related deaths of 0.64%. The combined minor and major strokes and procedure‐related death rate was 3.98% based on procedure number. With nonprocedure‐related death rate of 0.77%, the total stroke and death rate was 4.75%. Subsets of questions were directed at the new use of distal embolic protection devices; there were 6,753 cases done without protection and which incurred a 5.29% rate of strokes and procedure‐related deaths. In the 4,221 cases with cerebral protection, there was a 2.23% rate of strokes and procedure‐related deaths. Restenosis rates of carotid stenting have been 2.7%, 2.6%, and 2.4% at 1, 2, and 3 years, respectively. The rate of neurologic events after stent placement has been 1.2%, 1.3%, and 1.7% at 1, 2, and 3 years, respectively. Endovascular stent treatment of carotid artery atherosclerotic disease is growing as an alternative for vascular surgery, especially for patients who are high risk for standard carotid endarterectomy. The periprocedure risks for major and minor strokes and death are generally acceptable at this early stage of development and have shown an improvement with technological developments, including distal embolic protection. Catheter Cardiovasc Interv 2003;60:259‐266
Broad scaling region in a spatial ecological system
Authors: Roy Manojit , Pascual Mercedes , Franc Alain
Published: September 2003

The ubiquity of scale‐free patterns in ecological systems has raised the possibility that these systems operate near criticality. Critical phenomena (CP) require the tuning of parameters and typically exhibit a narrow scaling region in which power laws hold. Here we show that an individual‐based predator‐prey model exhibits scaling properties similar to CP, generated by a percolation‐like transition but with a broader scaling region. There are no drastic changes in ecological quantities across this critical point and species coexist broadly in parameter space. The implications of these findings for the stability of ecological systems “near” criticality is discussed. © 2003 Wiley Periodicals, Inc.
Collective stochastic versions of playable games as metaphors for complex biosystems: Team connect four
Authors: Safro Il'Ya , Segel Lee
Published: September 2003

In an effort to better understand complex biological systems, the game “Connect Four” is generalized to be a stochastic contest between two teams. Members of each team typically possess “sensors” that provide some information on the nearby deployment of the pieces. Sensing something interesting increases the probability that a given team member will move. Simulations show the relative strengths of various sensor weightings and thereby cast some light on the use of sensors in more general complex autonomous systems. © 2003 Wiley Periodicals, Inc.
A hierarchy machine: Learning to optimize from nature and humans
Authors: Pelikan Martin , Goldberg David E.
Published: September 2003

This article proposes a competent hierarchical optimization method called the hierarchical Bayesian optimization algorithm (hBOA). hBOA extends the Bayesian optimization algorithm (BOA) by incorporating three important features for robust and scalable optimization of hierarchical problems: proper decomposition, chunking, and preservation of alternative solutions. Additionally, the article proposes a class of difficult hierarchical problems called hierarchical traps. hBOA is shown to provide a scalable solution to the class of hierarchically decomposable problems and anything easier. Specifically, hBOA can solve hierarchical traps and other nearly decomposable problems in approximately O(n1.55 log n) to O(n2) function evaluations, where n is the number of decision variables in the problem. © 2003 Wiley Periodicals, Inc.
The scale of perceived interpersonal closeness (PICS)
Authors: Popovic M. , Milne D. , Barrett P.
Published: September 2003

The development and piloting of a new scale entitled the Perceived Interpersonal Closeness Scale (PICS) is described. The format of the PICS requires an individual to position other individuals within a circular ‘closeness’ space in which the distance between these others can be mapped as an ordinal distance rating. By removing the reliance on verbal ratings, the PICS is designed to be easily understood by respondents. The PICS is specifically designed to measure individual perception of interpersonal (socio‐emotional) closeness and captures both the individual's actual and ideal sense of perceived closeness and social support. The results illustrate that the scale has satisfactory psychometric properties, including short‐term test–retest reliability (median value rs = 0.77), and acceptable face, concurrent and discriminant validity. It is proposed that this instrument is a pan‐theoretical and psychometrically sound assessment tool that can be clinically useful, regardless of therapeutic orientation. Copyright © 2003 John Wiley & Sons, Ltd.
People with delusions jump to conclusions: a theoretical account of research findings on the reasoning of people with delusions
Authors: Dudley R. E. J. , Over D. E.
Published: September 2003

Recent multifactorial models of psychotic symptoms such as delusions emphasize a role for reasoning biases in the maintenance of delusional beliefs. Specifically, people with delusions are seen to jump to conclusions. This well‐replicated experimental finding has received little in the way of theoretical explanation. In this paper we review this and other research findings examining reasoning of people with delusions and account for these findings by drawing on a model of reasoning. This theoretical integration helps understand the tendency of people with delusions to exhibit this reasoning style. Specifically, we propose that people without delusions demonstrate a normal tendency to confirm danger‐related conditional statements and that people with delusions perceive danger and threat where others do not. Hence, this normal reasoning style is extended to non‐threatening situations. The theoretical and clinical implications are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
What makes psychotherapy sessions productive? a new approach to bridging the gap between process research and practice
Authors: Smith Emma C. , Grawe Klaus
Published: September 2003

This paper proposes a new strategy for bridging the gap between psychotherapy process research and practice. Constructs covering the full spectrum of potential change mechanisms are derived from a general theory of human functioning (Grawe's Consistency Theory) and operationalized by Therapy Spectrum Analysis (TSA), a measure of the realization of therapeutic change mechanisms within individual therapy sessions. Using the data generated by TSA, we conducted an exploratory search for meaningful patterns of process and session‐outcome variables using Answer Tree as a context‐sensitive method of data analysis. Results show that process‐activated resources of the patients, in particular their responsiveness to interventions and motivation are especially predictive of the session productivity experienced. Further analyses were conducted to uncover how the patients' participation can be promoted and results translate into guidelines for the session‐to‐session decisions by clinicians. Copyright © 2003 John Wiley & Sons, Ltd.
Epicardium is required for the full rate of myocyte proliferation and levels of expression of myocyte mitogenic factors FGF2 and its receptor, FGFR‐1, but not for transmural myocardial patterning in the embryonic chick heart
Authors: Pennisi David J. , Ballard Victoria L.T. , Mikawa Takashi
Published: September 2003

Proper heart development requires patterning across the myocardial wall. Early myocardial patterning is characterized by a transmural subdivision of the myocardium into an outer, highly mitotic, compact zone and an inner, trabecular zone with lower mitotic activity. We have shown previously that fibroblast growth factor receptor (FGFR) ‐mediated signaling is central to myocyte proliferation in the developing heart. Consistent with this, FGFR‐1 and FGF2 are more highly expressed in myocytes of the compact zone. However, the mechanism that regulates the transmural pattern of myocyte proliferation and expression of these mitogenic factors is unknown. The present study examined whether this transmural patterning occurs in a myocardium‐autonomous manner or by signals from the epicardium. Microsurgical inhibition of epicardium formation in the embryonic chick gives rise to a decrease in myocyte proliferation, accounting for a thinner compact myocardium. We show that the transmural pattern of myocyte mitotic activity is maintained in these hearts. Consistent with this, the expression patterns of FGF1, FGF2, and FGFR‐1 across the myocardium persist in the absence of the epicardium. However, FGF2 and FGFR‐1 mRNA levels are reduced in proportion to the depletion of epicardium. The results suggest that epicardium‐derived signals are essential for maintenance of the correct amount of myocyte proliferation in the compact myocardium, by means of levels of mitogen expression in the myocardium. However, initiation and maintenance of transmural patterning of the myocardium occurs largely independently of the epicardium. Developmental Dynamics 228:161–172, 2003. © 2003 Wiley‐Liss, Inc.
Expression of mouse fibroblast growth factor and fibroblast growth factor receptor genes during early inner ear development
Authors: Wright Tracy J. , Hatch Ekaterina P. , Karabagli Hakan , Karabagli Pinar , Schoenwolf Gary C. , Mansour Suzanne L.
Published: September 2003

The inner ear, which mediates hearing and equilibrium, develops from an ectodermal placode located adjacent to the developing hindbrain. Induction of the placode and its subsequent morphogenesis and differentiation into the inner ear epithelium and its sensory neurons, involves signalling interactions within and between otic and non‐otic tissues. Several members of the fibroblast growth factor (FGF) family play important roles at various stages of otic development; however, there are additional family members that have not been evaluated. In this study, we surveyed the expression patterns of 18 mouse Fgf and 3 Fgf receptor (Fgfr) genes during early otic development. Two members of the Fgf family, Fgf4 and Fgf16, and all three tested members of the Fgfr family, Fgfr2c, Fgfr3c, and Fgfr4, were expressed in tissues relevant to inner ear development. Fgf4 transcripts were expressed in the preplacodal and placodal ectoderm, suggesting potential roles in placode induction and/or maintenance. Fgf16 was expressed in the posterior otic cup and vesicle, suggesting roles in otic cell fate decisions and/or axis formation. Development Dynamics 228:267–272, 2003. © 2003 Wiley‐Liss, Inc.
Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract
Authors: Yelbuz T. Mesud , Waldo Karen L. , Zhang Xiaowei , Zdanowicz Marzena , Parker Jeremy , Creazzo Tony L. , Johnson G. Allan , Kirby Margaret L.
Published: September 2003

Cardiac neural crest ablation results in primary myocardial dysfunction and failure of the secondary heart field to add the definitive myocardium to the cardiac outflow tract. The current study was undertaken to understand the changes in myocardial characteristics in the heart tube, including volume, proliferation, and cell size when the myocardium from the secondary heart field fails to be added to the primary heart tube. We used magnetic resonance and confocal microscopy to determine that the volume of myocardium in the looped heart was dramatically reduced and the compact layer of myocardium was thinner after neural crest ablation, especially in the outflow tract and ventricular regions. Proliferation measured by 5‐bromo‐2′‐deoxyuridine incorporation was elevated at only one stage during looping, cell death was normal and myocardial cell size was increased. Taken together, these results indicate that there are fewer myocytes in the heart. By incubation day 8 when the heart would have normally completed septation, the anterior (ventral) wall of the right ventricle and right ventricular outflow tract was significantly thinner in the neural crest‐ablated embryos than normal, but the thickness of the compact myocardium was normal in all other regions of the heart. The decreased volume and number of myocardial cells in the heart tube after neural crest ablation most likely reflects the amount of myocardium added by the secondary heart field. Development Dynamics 228:152–160, 2003. © 2003 Wiley‐Liss, Inc.
Identification and regulation of tissue‐specific cis‐acting elements associated with the human AP‐2α gene
Authors: Zhang J. , Williams T.
Published: September 2003

Mice lacking transcription factor AP‐2α exhibit defects in the formation of the head, body wall, heart, neural tube, eye, and limbs, reflecting important sites of AP‐2α expression in the developing embryo. AP‐2α is also expressed in the postnatal mammary gland and has been linked to tumor progression and defects in growth regulation in the breast. We have used a transgenic mouse approach to identify tissue‐specific cis‐acting sequences associated with expression of the human AP‐2α gene. Our analysis indicates that multiple elements located throughout the gene contribute to expression in the trigeminal ganglia, spinal cord, mammary gland, and epidermis. A discrete cis‐element located within the fifth intron is required for expression in the face and limbs, and we have derived a permanent line of AP‐2α::lacZ transgenic mice to assess expression of this latter enhancer throughout morphogenesis. We also introduced this transgene into an AP‐2α–null mouse background and detected subtle alterations of its expression within the progress zone and apical ectodermal ridge of the forelimbs. Similar changes in lacZ expression were observed within the zeugopod, and these correlated with defects in radius condensation in AP‐2α–knockout mice. Taken together, these findings indicate that cell:cell communication within the forelimb is altered in the absence of AP‐2α and reveal novel regulatory potential for AP‐2α in limb development. Developmental Dynamics 228:194–207, 2003. © 2003 Wiley‐Liss, Inc.
Expression of murine ELL‐associated factor 2 (Eaf2) is developmentally regulated
Authors: Li Min , Wu Xiangbing , Zhuang Fengfeng , Jiang Shaoyun , Jiang Meisheng , Liu Yi‐Hsin
Published: September 2003

Eaf2, ELL‐associated factor 2, encodes a protein that is homologous to the human EAF1, which was shown to interact with the transcriptional elongation factor MEN/ELL. During mouse embryogenesis, Eaf2 is preferentially expressed in the central nervous system and in sensory and neuroendocrine organs, including the brain, spinal cord, cranial and spinal ganglia, developing otocyst, the retina, and the pituitary. Eaf2 transcripts were also found in sites where active epithelium–mesenchymal interactions are occurring. These included the invaginating tooth buds, mammary gland anlage, submandibular glands, the lung, the pancreas, and the kidney. Other sites of expression included bladder and intestine. In the developing lens, Eaf2 transcripts were absent in the proliferating anterior lens epithelial cells but were present in the terminally differentiated primary lens fiber cells and also in nonproliferating lens fiber cells in the equatorial zone where lens epithelial cells withdraw from cell cycle and terminally differentiate into secondary lens fiber cells. This spatially restricted pattern of Eaf2 expression in the developing lens suggests that Eaf2 may play an important role in regulating lens maturation. Developmental Dynamics 228:273–280, 2003. © 2003 Wiley‐Liss, Inc.
Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells
Authors: Hart Alan , Papadopoulou Stella , Edlund Helena
Published: September 2003

The pancreas is an endodermally derived organ that initially appears as a dorsal and ventral protrusion of the primitive gut epithelium. The pancreatic progenitor cells present in these early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The fibroblast growth factor receptor (FGFR) 2b high‐affinity ligand FGF10 has been linked to pancreatic epithelial cell proliferation, and we have shown previously that Notch signalling controls pancreatic cell differentiation by means of lateral inhibition. In the developing pancreas, activated intracellular Notch appears to be required for maintaining cells in the progenitor state, in part by blocking the expression of the pro‐endocrine gene neurogenin 3 (ngn3), and hence endocrine cell differentiation. Here, we show that persistent expression of Fgf10 in the embryonic pancreas of transgenic mice also inhibits pancreatic cell differentiation, while stimulating pancreatic epithelial cell proliferation. We provide evidence that one of the effects of the persistent expression of Fgf10 in the developing pancreas is maintained Notch activation, which results in impaired expression of ngn3 within the pancreatic epithelium. Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch‐mediated lateral inhibition pathway. Developmental Dynamics 228:185–193, 2003. © 2003 Wiley‐Liss, Inc.
Growth/differentiation factor 5 enhances chondrocyte maturation
Authors: Coleman Cynthia M. , Tuan Rocky S.
Published: September 2003

Growth/differentiation factor 5 (GDF5) is required for limb mesenchymal cell condensation and joint formation during skeletogenesis. Here, we use a model consisting of long‐term, high‐density cultures of chick embryonic limb mesenchymal cells, which undergo the entire life history of chondrocyte development, to examine the effects of GDF5 overexpression on chondrocyte maturation. Exposure to GDF5 significantly enhanced chondrocyte hypertrophy and maturation, as determined by the presence of alkaline phosphatase activity, collagen type X protein production, and the presence of a sulfated proteoglycan‐rich extracellular matrix. Histologic analysis also revealed an increase in cell volume and cellular encasement in larger lacunae in GDF5‐treated cultures. Taken together, these results support a role for GDF5 in influencing chondrocyte maturation and the induction of hypertrophy in the late stages of embryonic cartilage development, and provide additional mechanistic insights into the role of GDF5 in skeletal development. Development Dynamics 228:208–217, 2003. Published 2003 Wiley‐Liss, Inc.
lunatic fringe regulates delta‐notch induction of hypochord in zebrafish
Authors: Appel Bruce , Marasco Paul , McClung Laura E. , Latimer Andrew J.
Published: September 2003

Cells that occupy the midline of vertebrate embryos arise from a common population of precursors. Several lines of evidence indicate that Delta‐Notch signaling regulates specification of midline precursors for different fates. We show that zebrafish midline precursors transiently express lunatic fringe, which encodes a glycosyltransferase that modifies Notch activity in response to its ligands, and that lunatic fringe function is required for Delta‐Notch–mediated induction of hypochord cells at the lateral borders of the midline precursor domain. Development Dynamics 228:281–286, 2003. © 2003 Wiley‐Liss, Inc.
Major role of BAX in apoptosis during retinal development and in establishment of a functional postnatal retina
Authors: Péquignot M.O. , Provost A.C. , Sallé S. , Taupin P. , Sainton K.M. , Marchant D. , Martinou J.C. , Ameisen J.C. , Jais J.‐P. , Abitbol M.
Published: September 2003

Apoptosis plays a major role in the development of the central nervous system. Previous studies of apoptosis induction during retinal development are difficult to interpret, however, because they explored different mouse strains, different developmental periods, and used different assays. Here, we first established a comprehensive sequential pattern of cell death during the whole development of the C57BL/6J mouse retina, from E10.5 to postnatal day (P) 21 by using the terminal deoxynucleotidyl transferase (TdT) ‐mediated deoxyuridine triphosphate (dUTP)–biotinylated nick end labeling (TUNEL) assay. We confirmed the existence of three previously described apoptotic peaks and identified another, later peak at P15, in both the outer nuclear layer, in which the photoreceptors differentiate, and the ganglion cell layer. Comparison of wild‐type C57BL/6 mice, gld mice, defective in the death ligand fasL, and bax‐/‐ mice, defective in the pro‐apoptotic BAX protein, revealed a minor role for FAS ligand but a crucial role for BAX in both apoptosis and normal retinal development. The lack of BAX resulted in thicker than normal inner neuroblastic and ganglion cell layers in adults, with larger numbers of cells and an impaired electroretinogram response related to a decreased number of responsive cells. Our findings indicate that cell death during normal retinal development is important for the modeling of a functional vision organ and showed that the pro‐apoptotic BAX protein plays a crucial role in this process. Developmental Dynamics 228:231–238, 2003. © 2003 Wiley‐Liss, Inc.
Involvement of hepatocyte growth factor in branching morphogenesis of murine salivary gland
Authors: Ikari Tatsuya , Hiraki Akimitsu , Seki Katsuhiro , Sugiura Tsuyoshi , Matsumoto Kunio , Shirasuna Kanemitsu
Published: September 2003

We investigated the involvement of hepatocyte growth factor (HGF) in salivary gland (SG) branching morphogenesis. The mouse submandibular gland (SMG) starts to develop at embryonic day 11.5–12 (E11.5–E12), and branching morphogenesis occurs in the area between the mandibular bone and tongue between E14 and E16.5. Real‐time reverse transcriptase‐polymerase chain reaction showed that the expression of the c‐met/HGF receptor gene in SMG increased and peaked between E14 and E16.5, concomitant with epithelial branching, and high levels of HGF mRNA were detected in the surrounding mesenchyme at E14–E15.5. Although strong expression of the HGF and c‐met transcripts was observed in the tongue muscles, this expression was limited at E13.5–E14.5. Serum‐free organ cultures were established, in which SG rudiments that contained SMG and sublingual gland (SLG) primordia (explant 1) and SMG/SLG rudiments with peripheral tissue that included part of the tongue muscle (explant 2) were isolated from E13.5 or E14 embryos. Mesenchyme‐free SMG epithelium was obtained by the removal of mesenchymal tissue from explant 1. In the explant 1 and 2 organ cultures, SMG/SLG rudiments showed growth and branching morphogenesis, while mesenchyme‐free epithelium failed to grow. When E13.5 or E14 mesenchyme‐free epithelium and a recombinant human HGF (rh‐HGF) ‐soaked bead were placed on Matrigel, the epithelium migrated toward the bead and formed branches, while the E13 epithelium failed to branch. The exogenous application of rh‐HGF and anti‐HGF antibody to the SMG/SLG rudiment cultures resulted in stimulation and inhibition, respectively, of branching morphogenesis. However, the response of E13.5 SMG to rh‐HGF was very weak, while the branching of E14 SMG was enhanced strongly by rh‐HGF. The branching morphogenesis of SMG was also inhibited by the addition of either antisense HGF or c‐met oligodeoxynucleotides to the cultures. The development of SMG in explant 2, which was significantly better than in explant 1, was comparable to that seen in vivo. Moreover, the expression of both HGF and c‐Met in the SMG of explant 2 was higher than in the SMG of explant 1. These findings provide the first demonstration that the branching morphogenesis of SMG is regulated by interactions with the surrounding mesenchyme‐derived HGF and c‐met expression in SMG, which occur concomitant with epithelial branching. The present data also suggest that the HGF that is released transiently from tongue muscles may contribute to the rapid development of SMG at the branching stage. Developmental Dynamics 228:173–184, 2003. © 2003 Wiley‐Liss, Inc.
Abundant and dynamic expression of G protein‐coupled P2Y receptors in mammalian development
Authors: Cheung Kwok‐Kuen , Ryten Mina , Burnstock Geoffrey
Published: September 2003

Extracellular ATP mediates diverse biological effects by activating two families of receptors, the P2X and P2Y receptors. There is growing evidence to show that activation of G protein‐coupled P2Y receptors can produce trophic effects in many cell types. Yet the expression and function of the P2Y receptors in development has rarely been studied and has never been investigated in mammalian development. This study used the reverse transcription‐polymerase chain reaction and immunohistochemistry to demonstrate the abundant and dynamic expression of P2Y receptors in rat development. These receptors were expressed in a wide range of embryonic structures, notably somites, skeletal muscle, the central and peripheral nervous system, the heart, lung, and liver. All the P2Y receptors studied were expressed as early as embryonic day 11, when most embryonic organs were far from being functional and still in the process of being formed. P2Y receptor proteins were strongly expressed in temporary, developmental structures that do not have a correlate in the adult animal, including the somites (P2Y1, P2Y2, and P2Y4) and the floor plate of the neural tube (P2Y1). P2Y receptors were also dynamically expressed, with receptor mRNA and protein being both up‐ and down‐regulated at different developmental stages. The down‐regulation of the P2Y1, 2, and 4 receptor proteins in skeletal muscle and heart, and the disappearance of the P2Y4 receptor from the brainstem and ventral white matter of the spinal cord postnatally, demonstrated that many P2Y receptors were likely to be involved in functions specific to embryonic life. Thus, these findings strongly suggest that P2Y receptors play an important role in the development of many tissues, and pioneer further studies into the role of purinergic signalling in development. Developmental Dynamics 228:254–266, 2003. © 2003 Wiley‐Liss, Inc.
Regionally distinct potencies of mouse XY genital ridge to initiate testis differentiation dependent on anteroposterior axis
Authors: Hiramatsu Ryuji , Kanai Yoshiakira , Mizukami Takuo , Ishii Maki , Matoba Shogo , Kanai‐Azuma Masami , Kurohmaru Masamichi , Kawakami Hayato , Hayashi Yoshihiro
Published: September 2003

In mouse gonadal differentiation, the center‐to‐pole Sry expression pattern suggests the regionally distinct potencies of the genital ridge, which induce testis differentiation. In this study, we examined the anteroposterior axis‐dependent differences in testis‐differentiation potencies by using cultures of anterior, middle, and posterior segments of the XY genital ridge. The inducible pattern of Sertoli cell differentiation showed a center‐to‐pole wave similar to the initial Sry expression pattern. In contrast, the ability to induce Leydig cell differentiation emanated from the anterior segment and then spread to the posterior side. These findings suggest the presence of two distinct dynamic waves in the capacity of the genital ridge to induce Sertoli or Leydig cell differentiation at early phases of testis differentiation. Developmental Dynamics 228:247–253, 2003. © 2003 Wiley‐Liss, Inc.
Patterning of the hyoid cartilage depends upon signals arising from the ventral foregut endoderm
Authors: Ruhin Blandine , Creuzet Sophie , Vincent Christine , Benouaiche Laurence , Le Douarin Nicole M. , Couly Gérard
Published: September 2003

Hyoid bone is a part of the visceral skeleton which arises from both Hox‐expressing (Hox+) and Hox‐nonexpressing (Hox‐) cephalic neural crest cells. In a previous work, we have demonstrated that the Hox‐ neural crest domain behaves as a naïve entity to which the ventral foregut endoderm confers patterning cues to specify the shape and orientation of the nasal and mandibular skeleton. By using ablation and grafting approaches, we have extended our study to the formation of the hyoid bone and tested the patterning ability of more caudal levels of the lateroventral foregut endoderm in the chick embryo at the early neurula stage. In this study, endodermal stripes have first been delineated according to the projection of mid‐ and posterior rhombencephalic structures. The extirpation of endodermal transverse stripes along the anteroposterior axis selectively hampers the formation of the ceratobranchials and epibranchials. Thus defined, the patterning ability of the endodermal stripes was further explored in their medial and lateral parts. When homotopically engrafted on the migration pathway of cephalic neural crest cells, ventromedial zones of endoderm lead to the formation of supernumerary basihyal and basibranchial, while lateral zones generate additional cartilaginous pieces recognizable as ceratobranchial and epibranchial. Taken together, our data demonstrate that, early in development, the ventral foregut endoderm exerts a regionalized patterning activity on the cephalic neural crest to build up the primary facial and visceral skeleton in jaws and neck and enable a map of the endodermal skeletogenic areas to be drawn. This map reveals that a cryptic metamerization of the anterior foregut endoderm precedes the formation of the branchial arches. Developmental Dynamics 228:239–246, 2003. © 2003 Wiley‐Liss, Inc.
Molecular mechanisms of early gut organogenesis: A primer on development of the digestive tract
Authors: Kiefer Julie C.
Published: September 2003

Creating an organ poses unique challenges in embryogenesis, including establishing an organ primordium and coordinating development of different tissues in the organ. The digestive tract (gut) is a complex organ system, posing the interesting question of how the development of a series of organs is coordinated to establish an organ system with a common function. Although gut development has been the focus of much research, the molecular mechanisms that regulate these events are just beginning to be understood. This primer will first outline the basic anatomy of the digestive tract and then focus on molecular mechanisms that drive vertebrate gut organogenesis. Deciphering mechanisms underlying gut organogenesis also provides insights into understanding the development of other organs. Developmental Dynamics 228:287–291, 2003. © 2003 Wiley‐Liss, Inc.
Effects of antisense misexpression of CFC on downstream flectin protein expression during heart looping
Authors: Linask Kersti K. , Han Ming‐Da , Linask Kaari L. , Schlange Thomas , Brand Thomas
Published: September 2003

Dextral looping of the heart is regulated on multiple levels. In humans, mutations of the genes CFC and Pitx2/RIEG result in laterality‐associated cardiac anomalies. In animal models, a common read‐out after the misexpression of laterality genes is heart looping direction. Missing in these studies is how laterality genes impact on downstream morphogenetic processes to coordinate heart looping. Previously, we showed that Pitx2 indirectly regulates flectin protein by regulating the timing of flectin expression in one heart field versus the other (Linask et al. [2002] Dev. Biol. 246:407–417). To address this question further we used a reported loss‐of‐function approach to interfere with chick CFC expression (Schlange et al. [2001] Dev. Biol. 234:376–389) and assaying for flectin expression during looping. Antisense CFC treatment results in abnormal heart looping or no looping. Our results show that regardless of the sidedness of downstream Pitx2 expression, it is the sidedness of predominant flectin protein expression in the extracellular matrix of the dorsal mesocardial folds and splanchnic mesoderm apposed to the foregut wall that is associated directly with looping direction. Thus, Pitx2 can be experimentally uncoupled from heart looping. The flectin asymmetry continues to be maintained in the secondary heart field during looping. Developmental Dynamics 228:217–230, 2003. © 2003 Wiley‐Liss, Inc.
Zwei neue fossile Hölzer der Morphogattung GinkgoxylonSaporta emend. Süss aus tertiären Schichten der Insel Lesbos, Griechenland, mit einer Übersicht über Fossilien mit ginkgoaler Holzstruktur
Authors: Süss H.
Published: September 2003

Die Geschichte der Morphogattung Ginkgoxylon Saporta wird diskutiert, ihre Diagnose verändert und aus dem Versteinerten Wald von Lesbos, Griechenland, werden zwei neue untermiozäne Ginkgoxyla als Ginkgoxylon lesboense sp. nova und G. diversicellulatum sp. nova beschrieben. In einer Übersicht sind die bisher bekannten Fossilien mit ginkgoaler Holzstruktur zusammengestellt. Außerdem werden die Ursachen, die zu schiefgestellten Holzstrahlen führen, diskutiert.
What is Sium frigidumHand.‐Mazz. (Umbelliferae)?
Authors: Pimenov M. G. , Kljuykov E. V.
Published: September 2003

A rare and enigmatic Chinese species, known as Apium ventricosum H. Boissieu and Sium frigidum Hand.‐Mazz. (the latter name is only used in current floristic literature), has been shown to be closer related to Sinocarum H. Wolff ex Shan RenHwa & Pu FaTing. This affinity, indicated recently by ITS sequence investigation, was confirmed by morphological analysis. Attribution of the species to Apium, Sium, or Chamaesium, was not confirmed by molecular and morphological data either. A new combination, Sinocarum ventricosum (H. Boissieu) Pimenov & Kljuykov, has been proposed. The isolated position of S. ventricosum within the genus Sinocarum is emphazised by separation of a new monotypic section, Sinocarum sect. Apiopsis Pimenov & Kljuykov.
Contribution to the knowledge of the Flora of the Mongolian Altai
Authors: Neuffer B. , Oyuntsetseg B. , Schamsran Z. , Friesen N. , Hurka H.
Published: September 2003

During a German‐Mongolian expedition to the Mongolian Altai in July/August 2000, 404 specimens of vascular plants were collected. They are deposited in the Herbarium of the University of Osnabrück (OSBU). 381 specimens could be determined conclusively. The collected material comprises 300 species, 156 genera, and 44 families. Six of these species were first records for Mongolia, six species had not been recorded so far for the region Mongolian Altai, five are new for the region Khobdo, and 19 species new records for both regions, Mongolian Altai and Khobdo, Western Mongolia. A list of the collected plants with accession numbers and provenances is presented.
Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer
Authors: Dabrosin Charlotta , Margetts Peter J. , Gauldie Jack
Published: September 2003

Angiogenesis is essential for tumor growth and metastasis and an important prognostic factor in breast cancer. VEGF, a key factor for angiogenesis, has been correlated with tumor vessel density in breast cancer. Estrogen, another crucial factor in breast cancer, stimulates VEGF; and an ERE in the VEGF gene has been defined. VEGF is bioactive in the extracellular fluid, where it becomes available to endothelial cells. Whether E2 affects VEGF levels in the extracellular fluid is not known. We show, using intratumoral microdialysis in vivo, that E2 treatment increased tumor extracellular levels of VEGF in an estrogen‐dependent breast cancer model. Moreover, extracellular levels of VEGF in the tumor showed a strong correlation with total tumor VEGF, contrary to plasma levels of VEGF. Ninety‐three percent of measured VEGF in the extracellular fluid in the tumor was tumor‐derived, while only 45% of VEGF in circulating plasma originated from the tumor. We conclude that E2 increases extracellular VEGF and that microdialysis is a sensitive method for measurement of local VEGF production in vivo. Our results have potential application to the assessment of tumor characteristics in vivo in human tumors for individualized cancer therapy. © 2003 Wiley‐Liss, Inc.