bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing fibroblast migration on discrete collagen threads for applications in tissue regeneration
Authors: Cornwell Kevin G. , Downing Brett R. , Pins George D.
Published: August 2004

Collagen threads with mechanical properties and fibrillar substructure similar to native tissue have been synthesized for the repair of injured tendon and ligament. While these scaffolding materials have demonstrated the potential for inducing tissue regeneration, one limitation has been an insufficient rate of tissue ingrowth for complete regeneration. We hypothesize that the structural hierarchy and biochemical cues on the surfaces of these threads will enhance the rate of cell migration and ultimately the rate of new tissue ingrowth. We developed an in vitro assay to measure the effects of various collagen sources and crosslinking on the rate of fibroblast migration on the surfaces of collagen threads. Threads were suspended from elevated platforms and seeded with fibroblast‐populated collagen lattices. Cell migration rates ranging from 0.75 to 1.25 mm/day were measured as the fibroblasts left the lattices and migrated onto various thread types. Threads self‐assembled from type I collagen were found to have migration rates similar to native tendon threads while crosslinking by severe dehydration decreased the rate. This novel in vitro model system allows examination of cell migration from a wound margin onto biomaterials to determine the effects of various cell types, matrix materials, and surface biochemistries on cell–matrix interactions. Ultimately, this assay will allow us to identify design parameters that will be most effective for enhancing the rate of tissue ingrowth on fiber‐based collagen scaffolds for soft tissue regeneration. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 55–62, 2004
Penetration depth into dental casting alloys by Nd:YAG laser
Authors: Baba N. , Watanabe I.
Published: August 2004

This study investigated the effect of laser‐beam welding conditions [voltage (V) and spot diameter (mm)] on the penetration depth into dental casting alloys. Castings (3.0 mm × 8.0 mm × 50 mm) were prepared from the metals used in this study: commercially pure titanium (CP Ti), Ti‐6Al‐4V, Ti‐6Al‐7Nb, cobalt–chromium alloy (Co–Cr) and Type IV gold alloy. Two cast blocks of each metal were butted against one another at the 8.0 × 50‐mm surfaces. They were then welded at their interface under the following conditions: voltage of 160–340 V, spot diameter of 0.4–1.6 mm, and pulse duration of 10 ms. After laser welding, the blocks were separated, and the penetration depth into each alloy was measured. The data were analyzed with the use of ANOVA at the p < 0.05 level of significance. The penetration depths were as follows: CP Ti (0.29–6.45 mm), Ti‐6Al‐4V (0.32–5.24 mm), Ti‐6Al‐7Nb (0.34–5.65 mm), Co–Cr (0.24–6.15 mm), and Type IV gold alloy (0.12–5.22 mm). The voltage and spot diameter affected the penetration depth into the metals tested. When the voltage increased and the spot diameter decreased, the penetration depth increased for each metal. Selecting suitable conditions for laser welding to obtain sufficient penetration depth for the optimal thickness of the metal is important when welding prostheses. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 64–68, 2005
Proinflammatory mediator expression in a novel murine model of titanium‐particle–induced intramedullary inflammation
Authors: Warme Bryan A. , Epstein Noah J. , Trindade Michael C. D. , Miyanishi Keita , Ma Ting , Saket Ramin R. , Regula Donald , Goodman Stuart B. , Smith R. Lane
Published: August 2004

Wear debris from total joint replacement prostheses is implicated in periprosthetic osteolysis and implant loosening. The pathophysiology of this biological process remains unclear. Animal models of particle‐induced osteolysis have proven useful in the study of specific tissue responses to wear debris. However, existing in vivo murine models of particle‐mediated inflammation do not permit analysis of cortical bone degradation. This study describes a murine model of particle disease using an intramedullary rod in the mouse femur to parallel the clinical situation. The model consists of placing a 10‐mm‐long Kirschner wire retrograde in both femurs of C57b1/6 male mice via a medial parapatellar arthrotomy. Phagocytosable titanium particles were also implanted unilaterally to replicate generation of wear debris. Mice were sacrificed at 2, 10, and 26 weeks and whole femurs were cultured for 72 h. Levels of interleukin‐6, monocyte chemotactic protein‐1, and macrophage colony stimulating factor were assayed by ELISA. Transverse histological sections, at the level of the implant, were taken and stained with hematoxylin and eosin (H&E). Results demonstrated increased expression of proinflammatory mediators at 2 weeks in femora with rod and particles compared to femora with rods alone. Destruction of the endosteum was evident at 2, 10, and 26 weeks in the femora with titanium. This novel murine model of particle‐induced intramedullary inflammation may facilitate cost‐effective genetic studies and offers investigators a simple, clinically relevant intramedullary model to readily examine the pathogenesis of particle‐mediated periprosthetic osteolysis. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 71B: 360–366, 2004
Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis
Authors: Lee Nikki P.Y. , Cheng C. Yan
Published: August 2004

Earlier studies in multiple epithelia have shown that cell–cell actin‐based adherens junction (AJ) dynamics are regulated, at least in part, by the interplay of kinases and phosphatases that determines the intracellular phosphoprotein content. Yet it is virtually unknown regarding the role of protein kinases in Sertoli–germ cell AJ dynamics in the seminiferous epithelium of the testis. To address this issue, an in vitro coculture system utilizing Sertoli and germ cells was used to study the regulation of several protein kinases, including c‐Src (the cellular form of the v‐src transforming gene of Rous Sarcoma virus, RSV), carboxyl‐terminal Src kinase (Csk), and casein kinase 2 (CK2), during AJ assembly. Both Sertoli and germ cells were shown to express c‐Src, Csk, and CK2 with a relative Sertoli:germ cell ratio of ∼1:1, suggesting both cell types contributed equally to the pool of these kinases in the epithelium. c‐Src and Csk were shown to be stage‐specific proteins during the epithelial cycle, being highest at stages VII–VIII. Studies using immunoprecipitation have illustrated that these kinases were structurally associated with the N‐cadherin/β‐catenin, but not the nectin/afadin, protein complex, implicating that the cadherin/catenin protein complex is their likely putative substrate. An induction in c‐Src, Csk, and CK2 were detected during Sertoli–germ cell AJ assembly in vitro but not when Sertoli cells were cultured alone. When adult rats were treated with 1‐(2,4‐dichlorobenzyl)‐indazole‐3‐carbohydrazide (AF‐2364), a compound known to induce germ cell loss from the seminiferous epithelium, in particular elongating/elongate and round spermatids, by disrupting Sertoli–germ cell AJs, an induction of c‐Src and Csk, but not CK2, was detected. Furthermore, a transient increase in the intrinsic kinase activities of c‐Src, but not CK2, was also detected. This event was also associated with a loss of protein–protein association of N‐cadherin and β‐catenin from the cadherin/catenin/c‐Src/Csk/CK2 protein complex. Administration of PP1, a c‐Src inhibitor, into adult rats via the jugular vein could induce the loss of spermatocytes and round spermatids, but not elongating/elongate spermatids, from the seminiferous epithelium. This result thus implicates the importance of c‐Src in maintaining the integrity of AJs and possibly desmosome‐like junctions between Sertoli cells and spermatocytes/round spermatids. In short, the data reported herein have shown that c‐Src, Csk, and CK2 are novel protein kinases in AJ dynamics in the testis. © 2004 Wiley‐Liss, Inc.
Alpha‐interferon and its effects on signal transduction pathways
Authors: Caraglia Michele , Marra Monica , Pelaia Girolamo , Maselli Rosario , Caputi Mario , Marsico Serafino A. , Abbruzzese Alberto
Published: August 2004

Interferon‐α (IFNα) is a recombinant protein widely used in the therapy of several neoplasms such as myeloma, renal cell carcinoma, epidermoid cervical and head and neck tumors, and melanoma. IFNα, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of cancer cell growth and differentiation, affecting cellular communication and signal transduction pathways. However, the way by which tumor cell growth is directly suppressed by IFNα is not well known. Wide evidence exists on the possibility that cancer cells undergo apoptosis after the exposure to the cytokine. Here we will review the consolidate signal transducer and activator of transcription (STAT)‐dependent mechanism of action of IFNα. We will discuss data obtained by us and others on the triggering of the stress‐dependent kinase pathway induced by IFNα and its correlations with the apoptotic process. The regulation of the expression of proteins involved in apoptosis occurrence will be also described. In this regard, IFNα is emerging as a post‐translational controller of the intracellular levels of the apoptosis‐related protein tissue transglutaminase (tTG). This new way of regulation of tTG occurs through the modulation of their proteasome‐dependent degradation induced by the cytokine. Until today, inconsistent data have been obtained regarding the clinical effectiveness of IFNα in the therapy of solid tumors. In fact, the benefit of IFNα treatment is limited to some neoplasms while others are completely or partially resistant. The mechanisms of tumor resistance to IFNα have been studied in vitro. The alteration of JAK‐STAT components of the IFNα‐induced signaling, can be indeed a mechanism of resistance to IFN. However, we have recently described a reactive mechanism of protection of tumor cells from the apoptosis induced by IFNα dependent on the epidermal growth factor (EGF)‐mediated Ras/extracellular signal regulated kinase (Erk) signaling. The involvement of the Ras→Erk pathway in the protection of tumor cells from the apoptosis induced by IFNα is further demonstrated by both Ras inactivation by RASN17 transfection and mitogen extracellular signal regulated kinase 1 (Mek‐1) inhibition by exposure to PD098059. These data strongly suggest that the specific disruption of the latter could be a useful approach to potentiate the antitumour activity of IFNα against human tumors based on the new mechanistic insights achieved in the last years. © 2004 Wiley‐Liss, Inc.
Neurogenesis in the subventricular zone following transcranial magnetic field stimulation and nigrostriatal lesions
Authors: Arias‐Carrión O. , Verdugo‐Díaz L. , Feria‐Velasco A. , Millán‐Aldaco D. , Gutiérrez A.A. , Hernández‐Cruz A. , Drucker‐Colín R.
Published: August 2004

Neurogenesis continues at least in two regions of the mammalian adult brain, the subventricular zone (SVZ) and the subgranular zone in hippocampal dentate gyrus. Neurogenesis in these regions is subjected to physiological regulation and can be modified by pharmacological and pathological events. Here we report the induction of neurogenesis in the SVZ and the differentiation after nigrostriatal pathway lesion along with transcranial magnetic field stimulation (TMFS) in adult rats. Significant numbers of proliferating cells demonstrated by bromodeoxyuridine‐positive reaction colocalized with the neuronal marker NeuN were detected bilaterally in the SVZ, and several of these cells also expressed tyrosine hydroxylase. Transplanted chromaffin cells into lesioned animals also induced bilateral appearance of subependymal cells. These results show for the first time that unilateral lesion, transplant, and/or TMFS induce neurogenesis in the SVZ of rats and also that TMFS prevents the motor alterations induced by the lesion. © 2004 Wiley‐Liss, Inc.
Thermally Produced Biodegradable Scaffolds for Cartilage Tissue Engineering
Authors: Lee Soo‐Hong , Kim Byung‐Soo , Kim Soo Hyun , Kang Sun Woong , Kim Young Ha
Published: August 2004

Summary: A novel process was developed to fabricate biodegradable polymer scaffolds for tissue engineering applications, without using organic solvents. Solvent residues in scaffolds fabricated by processes involving organic solvents may damage cells transplanted onto the scaffolds or tissue near the transplantation site. Poly(L‐lactic acid) (PLLA) powder and NaCl particles in a mold were compressed and subsequently heated at 180 °C (near the PLLA melting temperature) for 3 min. The heat treatment caused the polymer particles to fuse and form a continuous matrix containing entrapped NaCl particles. After dissolving the NaCl salts, which served as a porogen, porous biodegradable PLLA scaffolds were formed. The scaffold porosity and pore size were controlled by adjusting the NaCl/PLLA weight ratio and the NaCl particle size. The characteristics of the scaffolds were compared to those of scaffolds fabricated using a conventional solvent casting/particulate leaching (SC/PL) process, in terms of pore structure, pore‐size distribution, and mechanical properties. A scanning electron microscopic examination showed highly interconnected and open pore structures in the scaffolds fabricated using the thermal process, whereas the SC/PL process yielded scaffolds with less interconnected and closed pore structures. Mercury intrusion porosimetry revealed that the thermally produced scaffolds had a much more uniform distribution of pore sizes than the SC/PL process. The utility of the thermally produced scaffolds was demonstrated by engineering cartilaginous tissues in vivo. In summary, the thermal process developed in this study yields tissue‐engineering scaffolds with more favorable characteristics, with respect to, freedom from organic solvents, pore structure, and size distribution than the SC/PL process. Moreover, the thermal process could also be used to fabricate scaffolds from polymers that are insoluble in organic solvents, such as poly(glycolic acid).

Cartilage tissue regenerated from thermally produced PLLA scaffold.

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Cartilage tissue regenerated from thermally produced PLLA scaffold.
The Development of Stereoerrors During the Homo‐ and Copolymerization of Propylene Using C2‐Symmetric Metallocene Catalysts – A Cautionary Note
Authors: van Reenen Albert J. , Lutz Marietjie
Published: August 2004

Summary: A recent paper described the development of atactic sequences during the copolymerization of propylene and 1‐pentene using the C2‐symmetric metallocene catalyst rac‐dimethylsilyl‐bis(2‐methylbenz(e)indenyl) zirconium dichloride. We have found similar stereoerrors, and showed that atactic material could in fact be extracted from the material, indicating that the catalyst in question had probably isomerized in solution, leading to a mixture of isotactic and atactic polymers.

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Phase Composition and Molecular Mobility in Nylon 6 Fibers as Studied by Proton NMR Transverse Magnetization Relaxation
Authors: Litvinov Victor M. , Penning Jan Paul
Published: August 2004

Summary: The phase composition and molecular mobility of Nylon 6 fibers has been studied using 1H solid‐state NMR transverse magnetization relaxation (T2 relaxation) spectroscopy. One of the objectives of this work is to determine the usefulness of the NMR relaxation method to accurately determine the crystallinity of Nylon 6 fibers. The NMR relaxation results have been interpreted using a three‐phase model, which is proposed on the basis of distinct differences in chain mobility in the crystalline phase, the semi‐rigid crystal‐amorphous interface, and the soft amorphous phase. In order to obtain accurate data on the phase composition, the effects of absorbed water and annealing of fibers at elevated temperatures were studied in detail. It was shown that water mainly plasticizes the soft fraction of the amorphous phase. Changes in the phase composition and molecular mobility caused by fiber annealing at elevated temperatures were studied with real‐time NMR T2 relaxation experiments. The most pronounced annealing effects (changes in the phase composition) were observed for undrawn fibers with low molecular orientation. Annealing slows down for fibers produced at larger winding speed and especially those with a high draw ratio. Fiber processing conditions, i.e., winding speed and draw ratio, are found to affect the phase composition and molecular mobility in different phases. It was shown that the present NMR relaxation method provides a fast and accurate technique to analyze the phase composition of Nylon 6 fibers. The amount of rigid phase determined from NMR is in good agreement with the crystallinity of the fiber obtained using the traditional method for Nylon 6 fibers, which involves a combination of density measurement, wide‐angle X‐ray diffraction and 13C NMR spectroscopy. Hence, the present NMR relaxation method greatly simplifies measurement of crystallinity in Nylon 6 fibers.

The effect of draw ratio on the phase composition in Nylon 6 fibers as studied by NMR and the traditional method.

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The effect of draw ratio on the phase composition in Nylon 6 fibers as studied by NMR and the traditional method.
Diblock Copolymers Based on 1,4‐Dioxan‐2‐one and ε‐Caprolactone: Characterization and Thermal Properties
Authors: Raquez Jean‐Marie , Degée Philippe , Narayan Ramani , Dubois Philippe
Published: August 2004

Summary: Various poly(ε‐caprolactone‐block‐1,4‐dioxan‐2‐one) (P(CL‐block‐PDX)) block copolymers were prepared according to the living/controlled ring‐opening polymerization (ROP) of 1,4‐dioxan‐2‐one (PDX) as initiated by in situ generated ω‐aluminium alkoxides poly(ε‐caprolactone) (PCL) chains in toluene at 25 °C.1 1H NMR, PCS and TEM measurements have attested for the formation of colloids attributed to a growing PPDX core surrounded by a solvating PCL shell during the polymerization of PDX promoted by ω‐Al alkoxide PCL chains in toluene. The thermal behavior of the P(CL‐block‐PDX) copolymers was studied by DSC; showing two distinct melting temperatures (as well as two glass transition temperatures) similar to those of the respective homopolyesters. Finally, the thermal degradation of the P(CL‐block‐PDX) block copolymers was investigated by TGA simultaneously coupled to a FT‐IR spectrometer and a mass spectrometer for evolved gas analysis (EGA). The degradation occurred in two consecutive steps involving a first unzipping depolymerization of the PPDX blocks followed by the degradation of the PCL blocks via both ester pyrolysis and unzipping reactions.

TEM observation of P(CL‐block‐PDX) block copolyesters ($\overline M _{{\rm nPCL}}$ = 11 600 and $\overline M _{{\rm nPPDX}}$ = 22 100) as formed by vaporization starting from a diluted suspension in toluene/TCE mixture solvent (50/50 v/v).

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TEM observation of P(CL‐block‐PDX) block copolyesters ($\overline M _{{\rm nPCL}}$ = 11 600 and $\overline M _{{\rm nPPDX}}$ = 22 100) as formed by vaporization starting from a diluted suspension in toluene/TCE mixture solvent (50/50 v/v).
Synthesis and Characterization of Polymer Brushes on Micromechanical Cantilevers
Authors: Bumbu Gina‐Gabriela , Kircher Gunnar , Wolkenhauer Markus , Berger Rüdiger , Gutmann Jochen S.
Published: August 2004

Summary: A technique to cover microelectromechanical systems (MEMS), such as micromechanical cantilever (MC) sensors, with a covalently bound brush layer has been developed. The polymer layer was grown using a “grafting‐from” synthesis of polymer brushes under mild conditions, by surface‐initiated atom transfer radical polymerization. Atomic force microscopy (AFM) and ellipsometry have revealed a uniform thickness of about 12 nm from which a grafting density of polymer brushes of 0.19 chains · nm−2 was estimated. The coating with polymer brushes can be realized on a selected surface. It was shown that a single‐sided brush layer swells reversibly in toluene, resulting in a bending of the micromechanical cantilever.

Schematic representation of the PMMA brush synthesis on the MC surface, by surface‐initiated ATRP.

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Schematic representation of the PMMA brush synthesis on the MC surface, by surface‐initiated ATRP.
Cover Picture: Macromol. Chem. Phys. 12/2004
Authors: Kitano Hiromi , Hirabayashi Tadashi , Gemmei‐Ide Makoto , Kyogoku Mayumi
Published: August 2004

Front Cover: The picture on the cover shows the coil‐globule transition of the graft polymer with increasing temperature, and the change of lower critical solution temperature (LCST) upon the formation of polypseudorotaxane of grafted poly(ethylene glycol) with sulfonated calixarene. It can be understood well from this graphics that the LCST of the graft polymer significantly changes due to the formation of polypseudorotaxane (blue broken line: graft polymer solution, wine red broken line: graft polymer‐calixarene mixture).

Further details can be found in the Full Paper by H. Kitano,* T. Hirabayashi, M. Gemmei‐Ide, and M. Kyogoku on page 1651.
Gelation Studies: Comparison of the Critical Exponents Obtained by Dynamic Light Scattering and Rheology, 2
Authors: Richter Sven , Boyko Volodymyr , Matzker Rolf , Schröter Klaus
Published: August 2004

Summary:The sol–gel transition of two thermoreversible gelling mixtures made of xanthan gum and locust‐bean gum has been studied by using in situ, time‐resolved dynamic light scattering (DLS) and in situ rheology. A critical dynamical behavior was observed near the sol–gel transition, which was characterized by the presence of power‐law spectra over three and four decades in the time‐intensity correlation functiong2(t) − 1 ∼ t−μand over four and three decades in the oscillatory shear experimentG′(ω) ∼ G″(ω) ∼ ωn. A comparison of the critical exponents obtained (μ1 ≈ 0.36, μ2 ≈ 0.32 andn1 ≈ 0.62,n2 ≈ 0.67) was made as a function of the dependence of the two mixing ratios according to the theory by Doi and Onuki. New experiments were also performed to compare the critical exponents on such a thermoreversible system.

Double‐logarithmic plot of the time‐intensity correlation functionsg2(t) − 1 versus the delay time,t, at a 90° scattering angle and at several temperatures of the mixture 1.

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Double‐logarithmic plot of the time‐intensity correlation functionsg2(t) − 1 versus the delay time,t, at a 90° scattering angle and at several temperatures of the mixture 1.
Accurate mass measurements by Fourier transform mass spectrometry
Authors: Zhang Li‐Kang , Rempel Don , Pramanik Birendra N. , Gross Michael L.
Published: August 2004

The capability for accurate mass measurements is an important attribute of Fourier transform mass spectrometry (FTMS). Unlike other instrumental methods in mass spectrometry, FTMS still offers significant opportunities to improve mass measurement accuracy (MMA), making it an area of research. This review covers the published literature in FTMS from the late 1970s to the present. We discuss the development and evolution of mass calibration that give accuracies in the low ppm range. We sketch the derivation and show the common foundation of these mass calibration procedures. We also describe the relation of mass calibration and the fundamentals of ion motion and space‐charge effects, and we review efforts to improve the basic calibration procedure particularly those that correct for effects of space charge. The advent of matrix‐assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) have opened the door for FTMS to be used for analyzing at high performance biopolymers, including proteins, oligodeoxynucleotides (ODNs), oligosaccharides, and synthetic polymers. We also discuss the utility of FTMS for accurate mass measurement in these areas and some practical ways to improve MMA. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:286–309, 2005
A novel family with an unusual early‐onset generalized dystonia
Authors: Fabbrini Giovanni , Brancati Francesco , Vacca Laura , Valente Enza Maria , Nemeth Andrea , Meesaq Angela , Sykes Nuala , Dallapiccola Bruno , Berardelli Alfredo
Published: August 2004

We report on an Italian family in which three brothers and their maternal grandfather had a generalized early‐onset dystonia with mild parkinsonian signs. Genetic testing excluded the rapid‐onset dystonia‐parkinsonism locus (DYT12; OMIM*128235), autosomal recessive Parkin locus (PARK2; OMIM *602544), and DYT1 dystonia. Three affected siblings were found to share an identical haplotype at the X‐linked dystonia–parkinsonism locus (XDP; Lubag; OMIM*314250). This haplotype differed from the haplotype observed in Filipino patients, ruling out the hypothesis of a common underlying mutation. In addition, direct sequencing analysis of the putative disease causing changes observed in Filipino patients were not found in the Italian patients. The condition we describe could be a newly recognized dystonia syndrome with parkinsonism. © 2004 Movement Disorder Society
Cannabis sativa and dystonia secondary to Wilson's disease
Authors: Uribe Roca M. Claudia , Micheli Federico , Viotti Ricardo
Published: August 2004

A patient with generalized dystonia due to Wilson's disease obtained marked improvement in response to smoking cannabis. © 2004 Movement Disorder Society
Chewing pattern in patients with Meige's syndrome
Authors: Mascia Marcello M. , Valls‐Solé Josep , Martí Maria J. , Sanz Sergio
Published: August 2004

Meige's syndrome presents with a combination of upper and lower facial motor dysfunction, including eye closing spasms and oromandibular dystonia. While the pathophysiology of eye closing spasms has been extensively studied using the blink reflex and other trigeminofacial reflexes, very few studies have been carried out with regard to the abnormal perioral movements. We hypothesized that action‐related dystonic features could be revealed by the analysis of the semiautomatic rhythmic movements required for chewing and swallowing. A total of 7 patients with Meige's syndrome that complained of chewing problems and 7 age‐matched healthy volunteers were studied. Subjects were instructed to munch and swallow a small muffin while surface electromyographic (EMG) activity of masseter (MAS) and orbicularis oris (OOr) of the dominant side was recorded. In healthy subjects, MAS and OOr showed a rhythmic alternating phasic EMG pattern during chewing, which changed to a tonic cocontraction of both muscles during swallowing. Mean duration of MAS and OOr EMG bursts was, respectively, 297 ± 28 msec and 328 ± 29 msec. Patients exhibited the following alterations: excess duration of muscle activity, frequent cocontraction, loss of rhythmicity during chewing, and abnormalities in the chewing to swallowing transition phase. These abnormalities, similar in type to those encountered in other forms of focal dystonia, may be the expression of an abnormal motor control of basal ganglia over mastication‐related movement pattern generators of the brainstem. © 2004 Movement Disorder Society
Left hemibody myoclonus due to anomalous right vertebral artery
Authors: Coelho Miguel , Marti Maria J. , Valls‐Solé Josep , Pujol Teresa , Tolosa Eduardo
Published: August 2004

A 43‐year‐old man presented with sporadic, sudden, brief, and involuntary jerks of his left limbs and trunk muscles. The electromyographic recordings showed short‐lasting highly synchronized bursts, compatible with myoclonus limited to the left hemibody. Blink reflex, masseter silent period, cortical and spinal magnetic stimulation, somatosensory cortical evoked potentials, and electroencephalogram (EEG) were normal; the EEG back‐averaging showed no spikes preceding the myoclonus. Magnetic resonance imaging and magnetic resonance angiography showed the presence of an anomalous nonectasic right vertebral artery compressing the right side of ventral medulla oblongata. We hypothesize that the aberrant right vertebral artery induced abnormal activation of descending motor tracts responsible for the myoclonus. © 2004 Movement Disorder Society
Dyskinesias due to intravenous apomorphine abuse in a patient without basal ganglia disorder
Authors: Happe Svenja , Sommer Martin , Meller Johannes , Trenkwalder Claudia , Paulus Walter
Published: August 2004

Dyskinesias are known to occur in many patients with Parkinson's disease treated with dopaminergic drugs but to date, drug‐induced dyskinesias have not been observed in humans with no underlying basal ganglia disorder. We describe a patient with psychogenic parkinsonism and intravenous apomorphine abuse leading to subsequent choreatiform dyskinesias. © 2004 Movement Disorder Society
13C and 1H nuclear magnetic resonance of methyl‐substituted acetophenones and methyl benzoates: steric hindrance and inhibited conjugation
Authors: Buděšínský Miloš , Kulhánek Jiří , Böhm Stanislav , Cigler Petr , Exner Otto
Published: August 2004

The 1H and 13C NMR spectra of 14 methyl‐substituted acetophenones and 14 methyl‐substituted methyl benzoates were assigned and interpreted with respect to the conformation of the Car—C(O) bond. The substituent effects are proportional in the two series and can be divided into polar and steric: each has different effects on the 13C SCS of the individual atoms. In the case of C atoms C(O), C(1) and CH3(CO), the steric effects were quantitatively separated by comparing SCS in the ortho and para positions. The steric effects are proportional for the individual C atoms and also to steric effects estimated from other physical quantities. However, they do not depend simply on the angle of torsion ϕ of the functional group as anticipated hitherto. A better description distinguishes two classes of compounds: sterically not hindered or slightly hindered planar molecules and strongly sterically hindered, markedly non‐planar. In order to confirm this reasoning without empirical correlations, the J(C,C) coupling constants were measured for three acetophenone derivatives labeled with 13C in the acetyl methyl group. The constants confirm unambiguously the conformation of 2‐methylacetophenone; their zero values are in accord with the conformation of 2,6‐dimethylacetophenone. The zero values in the unsubstituted acetophenone are at variance with previous erroneous report but all J(C,C) values are in accord with calculations at the B3LYP/6‐311++G(2d,2p)//B3LYP/6–311+G(d,p) level. Copyright © 2004 John Wiley & Sons, Ltd.
An experimental and theoretical study of the Cp2VO2CO: use of 13CO32− for structure investigation of d1‐metallocene complexes
Authors: Vinklárek Jaromír , Honzíček Jan , Holubová Jana
Published: August 2004

EPR study has shown that the anticancer agent vanadocene dichloride (Cp2VCl2) interacts with carbonate contained in physiological solutions. Chelate complex Cp2VO2CO (|Aiso(51V)| = 175.1 MHz, giso = 1.9861) is the only paramagnetic species formed in the range about the physiological pH (5.5–11.0). The super‐hyperfine coupling (|aiso(13C)| = 24.1 MHz) was evidenced at measurements using 13C labelled carbonate. The structure of carbonate complex was validated by comparison of observed and theoretical calculated HFC tensors (at the density functional level of theory). Copyright © 2004 John Wiley & Sons, Ltd.
Electron spin resonance study of phosphorus‐nitroxides from 1,3‐additions of silicon‐phosphorus reagents to nitrones
Authors: Haire D. Lawrence , Janzen Edward G. , Robinson Valerie J. , Hrvoic Ivan
Published: August 2004

This article explores a new, convenient route to β‐phosphorus nitroxides. Specifically, the reaction sequence involves the novel 1,3‐addition of trimethylsilyl phosphites (e.g. diethyl) or trimethylsilyl phosphines (e.g. diphenyl) to aldo‐nitrones [e.g. α‐phenyl‐N‐tert‐butylnitrone (PBN) or 5,5‐dimethyl‐l‐pyrroline‐N‐oxide (DMPO)] or keto‐nitrones [e.g. 2‐ethyl‐5,5‐dimethyl‐1 pyrroline‐N‐oxide (2‐Et‐DMPO) or 2‐phenyl‐5,5‐dimethyl‐l‐pyrroline‐N‐oxide (2‐Ph‐DMPO)] to form α‐phosphityl‐ or α‐phosphinyl‐O‐silylhydroxylamines. Acidic hydrolysis provides the corresponding hydroxylamines that are easily oxidized to the title β‐phosphorus‐nitroxides. ESR spectroscopic analysis revealed some very large β‐phosphorus hyperfine splittings (i.e. in excess of 5 mT). For this reason and their remarkable stability (persistence) some of these nitroxides show promise as integral components in new, improved weak‐field dynamic nuclear polarization (DNP) magnetometers. Copyright © 2004 John Wiley & Sons, Ltd.
Conformational evaluation and detailed 1H and 13C NMR assignments of eremophilanolides
Authors: Burgueño‐Tapia Eleuterio , Hernández Luis R. , Reséndiz‐Villalobos Adriana Y. , Joseph‐Nathan Pedro
Published: August 2004

Extensive application of 1D and 2D NMR methodology, combined with molecular modeling, allowed the complete 1H and 13C NMR assignments of eremophilanolides from Senecio toluccanus. Comparison of the experimental 1H, 1H coupling constant values with those generated employing a generalized Karplus‐type relationship, using dihedral angles extracted from MMX and DFT calculations, revealed that the epoxidized eremophilanolides 1 and 2 show conformational rigidity at room temperature, whereas molecules 3–6, containing an isolated double bond, are conformationally mobile. Copyright © 2004 John Wiley & Sons, Ltd.
13C CP/MAS NMR studies of vitamin E model compounds
Authors: Witkowski Stanislaw , Paradowska Katarzyna , Wawer Iwona
Published: August 2004

13C cross‐polarization magic angle spinning (CP/MAS) NMR data for 2,2,5,7,8‐pentamethylchroman‐6‐ol (2), 6‐hydroxy‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid (Trolox c) (3) and its acetate (4), 2‐methoxy‐2,2,5,7,8‐pentamethylchroman‐6‐ol (5), 2‐hydroxy‐2,2,5,7,8‐pentamethylchroman‐6‐ol (6) and 2,2,5,7,8‐pentamethylchroman (7) are reported. A deshielding of 7.7 ppm for the carboxylic carbon was observed in solid Trolox due to formation of intermolecular hydrogen bonds within cyclic dimers. Such crystal packing permits effective cross‐polarization and fast relaxation (short T1ρH). The impact of the proton concentration on the CP dynamics is reflected by the longer TCP and T1ρH for Trolox‐d2 (deuterated at mobile proton sites). The calculated GIAO RHF shielding constants are sensitive to intramolecular effects: rotation around the C‐6O bond (changes of σ up to 8 ppm) and conformation at C‐2. Copyright © 2004 John Wiley & Sons, Ltd.
Exact likelihood inference for the exponential distribution under generalized Type‐I and Type‐II hybrid censoring
Authors: Chandrasekar B. , Childs A. , Balakrishnan N.
Published: August 2004

Chen and Bhattacharyya [Exact confidence bounds for an exponential parameter under hybrid censoring, Commun Statist Theory Methods 17 (1988), 1857–1870] considered a hybrid censoring scheme and obtained the exact distribution of the maximum likelihood estimator of the mean of an exponential distribution along with an exact lower confidence bound. Childs et al. [Exact likelihood inference based on Type‐I and Type‐II hybrid censored samples from the exponential distribution, Ann Inst Statist Math 55 (2003), 319–330] recently derived an alternative simpler expression for the distribution of the MLE. These authors also proposed a new hybrid censoring scheme and derived similar results for the exponential model. In this paper, we propose two generalized hybrid censoring schemes which have some advantages over the hybrid censoring schemes already discussed in the literature. We then derive the exact distribution of the maximum likelihood estimator as well as exact confidence intervals for the mean of the exponential distribution under these generalized hybrid censoring schemes. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004
Trade‐offs on the location of the core node in a network
Authors: Macq Jean‐François , Goemans Michel X.
Published: August 2004

We consider the problem of selecting a core node in a network under two potentially competing criteria, one being the sum of the distances to a set of terminals, the other being the cost of connecting this core node and the terminals with a Steiner tree. We characterize the worst‐case trade‐off between approximation ratios for the two objectives. Our results, for example, show the existence of a core node in which both objectives are simultaneously within 1.37 times their optimum value (if we were to disregard the other objective). We also consider the problem of minimizing a weighted sum of the two criteria and perform a worst‐case analysis of a simple and fast heuristic, which does not need to enumerate possible core locations. This study was motivated by multimedia applications such as videoconferences or multiplayer games in which user‐dependent information has to be sent from the users to a core node to be chosen (at a cost proportional to the sum of the distances from the core node), and then global information has to be multicast back from the core node to all users (at a cost proportional to the Steiner tree cost). © 2004 Wiley Periodicals, Inc. NETWORKS, Vol. 44(3), 179–186 2004
The ring grooming problem
Authors: Chow Timothy Y. , Lin Philip J.
Published: August 2004

The problem of minimizing the number of bidirectional SONET rings required to support a given traffic demand has been studied by several researchers. Here we study the relatedring‐groomingproblem of minimizing the number of add/drop locations instead of the number of rings; in a number of situations this is a better approximation to the true equipment cost. Our main result is a new lower bound for the case of uniform traffic. This allows us to prove that a certain simple algorithm for uniform traffic is, in fact, a constant‐factor approximation algorithm, and it also demonstrates that known lower bounds for the general problem—in particular, the linear programming relaxation—are not within a constant factor of the optimum. We also show that our results for uniform traffic extend readily to the more practically important case of quasi‐uniform traffic. Finally, we show that if the number of nodes on the ring is fixed, then ring grooming is solvable in polynomial time; however, whether ring grooming is fixed‐parameter tractable is still an open question. © 2004 Wiley Periodicals, Inc. NETWORKS, Vol. 44(3), 194–202 2004
Paired synovium and lymph nodes from rheumatoid arthritis patients differ in dendritic cell and chemokine expression
Authors: Page Guillaume , Miossec Pierre
Published: August 2004

The aim of this study was to compare the cellular composition and organization of rheumatoid (RA) synovium, which has several of the characteristics of lymphoid organs, with lymph nodes. To clarify further whether RA synovium can be classified as an ectopic lymphoid organ, paired RA synovium and lymph node (LN) tissues from 11 patients were compared in terms of T‐cell–B‐cell and germinal centre (GC) organization, dendritic cell (DC) subsets, and chemokine expression. Tonsil, a normal secondary lymphoid organ, was used as a tissue control. In paired RA LN and synovium, more follicular DC‐positive GCs were observed in LN, but when observed in synovium, they shared the same T‐cell–B‐cell organization and mean GC size. In LN, a predominance of mature DC‐LAMP‐positive DCs of myeloid (CD11c‐positive) or lymphoid (CD123‐positive) origin was observed, whereas paired RA synovium was characterized by the relative accumulation of immature CD1a‐positive DCs. In the same way, CCL19–CCL21/CCR7, a chemokine/chemokine receptor complex involved in mature DC migration, was more frequently seen in LN than in paired RA synovium. In synovium, such expression was associated with lymphoid follicle formation, with or without a GC. Conversely, CCL20, a chemokine involved in immature DC migration, was expressed in RA synovium and tonsils but not in paired LNs. In conclusion, although similarities were observed, this study, using paired samples, indicates that the RA synovium lacks some of the features that are characteristic of a lymphoid organ. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc
Authors: Le Maitre Christine Lyn , Freemont Anthony J , Hoyland Judith Alison
Published: August 2004

The histological and biochemical changes that occur in the extracellular matrix of the intervertebral disc (IVD) during ageing and degeneration have been investigated extensively. However, the mechanisms behind these changes are not fully understood. A number of studies have suggested the involvement of matrix metalloproteinases (MMPs) and ADAMTS in IVD degeneration, but few have localized the site of production of these enzymes to the cells of the degenerate disc. This study uses immunohistochemical techniques to localize and quantify the production of degrading enzymes (MMPs 1, 3, and 13, and ADAMTS 4) and their inhibitors (TIMPS 1, 2, and 3) within non‐degenerate and degenerate discs of varying severity of degeneration. In all discs investigated, the cells that produced the enzymes and their inhibitors were the chondrocyte‐like cells of the nucleus pulposus and inner annulus fibrosus (AF), with little immunopositivity in the outer AF. Non‐degenerate discs showed low numbers of cells expressing the degradative enzymes MMP 1 and ADAMTS 4, suggesting a role for these enzymes in normal homeostasis. No MMP 3 or MMP 13 immunopositivity was observed in non‐degenerate discs. In degenerate discs, the number of cells immunopositive for MMPs 1, 3, 13 and ADAMTS 4 increased with the severity of degeneration. This increase in degrading enzymes was also accompanied by increases in the number of cells immunopositive for TIMPs 1 and 2 but not TIMP 3. This study highlights that although the expression of a number of MMPs increases with degeneration, this is accompanied by an increase in their inhibitors. However, the increase in the number of cells immunoreactive for ADAMTS 4 with increasing degeneration was not paralleled by a rise in its inhibitor TIMP 3. This finding indicates that the aggrecanases, rather then the MMPs, are a possible therapeutic target for the inhibition of disc degeneration. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Altered cell kinetics in cultured placental villous explants in pregnancies complicated by pre‐eclampsia and intrauterine growth restriction
Authors: Crocker Ian P , Tansinda Dympna M , Baker Philip N
Published: August 2004

Placentae in pre‐eclampsia (PE) and intrauterine growth restriction (IUGR) are characterized by morphological variations, apoptosis, and syncytial shedding, features that are linked to inappropriate oxygen and inflammatory cytokines. Cell turnover within the placenta is dynamic. In this study, these cellular events have been investigated longitudinally using a placental explant model. Intrinsic variations between normal (n = 14), PE (n = 16) and IUGR pregnancies (n = 11), and their responses to oxygen (3% and 17%) and exogenous tumour necrosis alpha (TNFα), were recorded. Placental explants were assessed for apoptotic morphology, immunolocalization of MIB‐1 (a proliferation marker), lactate dehydrogenase (a necrosis marker), and human chorionic gonadotrophin (hCG, a marker of cytotrophoblast differentiation). Explants under TNFα and 17% O2 revealed progressive degeneration of syncytiotrophoblast (ST) followed by restoration of hCG, localized to newly differentiated cytotrophoblasts. This differentiation was significantly enhanced in PE and IUGR. Responses to 3% O2 were similar between groups: a sharp decline in hCG and failure to recover thereafter. Exaggerated cell death was recorded in PE and IUGR explants exposed to TNFα and 3% O2. All significant changes in apoptosis were confined to ST and stromal compartments. Enhanced cell death was predominantly apoptotic in PE and necrotic in IUGR. 3% O2 promoted cell proliferation in normal placentae but this response was not reciprocated in PE and IUGR. Elevated hCG in PE and IUGR explants may represent a placental predisposition to differentiation in vivo. In addition, the increased susceptibility of villous components to cell death, in the absence of stimulated proliferation, may provide a powerful mechanism for aberrant or adaptive placental cell turnover in utero. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome
Authors: Panigrahi AR , Pinder SE , Chan SY , Paish EC , Robertson JFR , Ellis IO
Published: August 2004

PTEN is a novel tumour suppressor gene located on chromosome 10. PTEN mutations are believed to exert their effects through the putative PI3K–AKT–mTOR signalling pathway. Specifically, loss of PTEN leads to activation of AKT, which in turn promotes anti‐apoptotic and pro‐cell cycle entry pathways believed to be essential in tumourigenesis. Whilst PTEN mutations are frequent in a variety of sporadic cancers and inherited cancer syndromes, it is not clear how frequently PTEN mutations and immunohistochemical loss of PTEN expression occur in sporadic breast cancer. This study used tissue microarrays (TMAs) to assess wild‐type PTEN and pAKT immunohistochemical staining in 670 and 691 cases, respectively, of primary operable breast cancer. Scores of 0, 1, and 2 were given for negative, weakly positive, and strongly positive degrees of immunoreactivity, respectively. In addition, immunohistochemical assessment of epidermal growth factor receptor (EGFR), Her2, and proliferation by MIB1 expression was performed on the same TMAs and the scores were compared with those of PTEN and pAKT. Eight per cent of cases did not express wild‐type PTEN. No correlation was observed between patient, tumour and outcome variables and PTEN. pAKT expression correlated inversely with adverse tumour variables such as tumour grade (p < 0.001) and correlated positively with ER status (p < 0.001). No correlation was seen between either PTEN or AKT and EGFR, Her2 or MIB1. No association of PTEN or pAKT was seen in Kaplan–Meier or multivariate analysis for overall survival. The results indicate that loss of PTEN expression is infrequent in breast cancer. PTEN and AKT do not appear to be prognostic markers. The study argues against the current model of a simple linear tumourigenic PTEN–PI3K–AKT–mTOR pathway in breast cancer. It also suggests that, in this group of breast cancers, the most common upstream regulator of AKT may be ER rather than PTEN, EGFR or Her2. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.