bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon
Authors: Chen Weisan , Masterman Kelly‐Anne , Basta Sameh , Mansour Haeryfar S. M. , Dimopoulos Nektaria , Knowles Barbara , Bennink Jack R. , Yewdell Jonathan W.
Published: February 2004

"Cross‐priming" refers to the activation of naive CD8+ T cells by antigen‐presenting cells that have acquired nominal antigens from another cell. The biological relevance of cross‐priming of CD8+ T cells has recently been challenged (Zinkernagel, R. M., Eur. J. Immunol. 2002. 32: 2385–2392), on the basis that responses are weak or poorly quantitated, and the determinants recognized are undefined. Here we show that cross‐priming is a robust process that elicits vigorous primary responses to multiple peptides in two well‐defined systems. Our findings support the relevance of cross‐priming in CD8+ T cell responses to viruses and tumor cells, and demonstrate that cross‐priming elicits CD8+ T cells to determinants generated by the endogenous processing pathway.
Arginase induction promotes Trypanosoma cruzi intracellular replication in Cruzipain‐treated J774 cells through the activation of multiple signaling pathways
Authors: Stempin Cinthia C. , Tanos Tamara B. , Coso Omar A. , Cerbán Fabio M.
Published: February 2004

Given that arginase activation may effectively influence nitric oxide (NO) production in macrophages, we have investigated the intracellular signals that regulate L‐arginine metabolism and its influence on Trypanosoma cruzi growth. We demonstrate that cruzipain (Cz), a parasite antigen, induces arginase I expression in J774 cells, and the pretreatment of Cz‐treated cells with N‐omega‐hydroxy‐L‐arginine (arginase inhibitor) leads to a dramatic decrease in amastigote growth. The study of intracellular signals shows that genistein [tyrosine kinase (TK) inhibitor], KT5720 [protein kinase (PK) A inhibitor] and SB203580 [p38 mitogen‐activated protein kinase (MAPK) inhibitor] significantly decrease Cz‐induced arginase activation. However, calphostin C (PKCinhibitor) and PD98059 [p44/p42 MAPK kinase (MEK) inhibitor] did not cause a significant change. To determine if signaling pathways triggered by Cz were involved in the T. cruzi growth, westudied the effect of those inhibitors. In Cz‐treated cells – pre‐incubated with TK, PKA or p38 MAPK inhibitors – the balance of NO/urea was biased towards NO, and the amastigote growth was diminished. Besides, genistein and mainly KT5720 induced down‐regulation of arginase I expression in Cz‐treated cells. Thus, activation of TK, PKA and p38 MAPK by Cz induces an increase of arginase activity in macrophages and the subsequent T. cruzi growth.
Drug‐induced autoantibody formation in mice: triggering by primed CD4+CD25– T cells, prevention by primed CD4+CD25+ T cells
Authors: Layland Laura E. , Wulferink Marty , Dierkes Sabine , Gleichmann Ernst
Published: February 2004

Although the ability of CD4+CD25+ T suppressor (Ts) cells to prevent experimental autoimmune diseases has been described, nothing is known concerning their role and mechanismof action in xenobiotic‐induced autoimmunity. Procainamide, mercuric chloride, and gold(I) are three xenobiotics that can induce autoimmune reactions in humans and rodents. After the induction of IgG1 antinuclear autoantibodies (ANA) in mice treated with either of the above xenobiotics, adoptive transfer of their CD4+CD25+ T cells completely prevented ANA formation in recipients treated with the same xenobiotic; transfer of CD8+ T cells was ineffective. Furthermore, xenobiotic‐primed CD4+CD25+ T cells could also partially prevent ANA formation in recipients treated with a different xenobiotic. CD4+CD25– T cells from xenobiotic‐treated donors failed to suppress, but induced de novo IgG1 ANA formation in untreated recipients. Our findings suggest that during xenobiotic treatment T cell reactivity may spread from xenobiotic‐induced, nucleoprotein‐related neoantigens to peptides of the unaltered nucleoproteins.
Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens
Authors: Nielsen Claus Henrik , Hegedüs Laszlo , Leslie Robert Graham Quinton
Published: February 2004

B cells are centrally involved as antigen‐presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self‐antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self‐antigen, sera from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture of IgG and C3 fragments. Furthermore, the binding of Tg to B cells in preparations of normal blood cells was higher in HT serum than in serum from controls and correlated positively with the serum anti‐Tg activity, as did the B and CD4+ T cell proliferation. Disruption of the three‐dimensional structure of Tg by boiling reduced the proliferative responses. The dataindicate that anti‐Tg antibodies associated with AITD facilitate the formation of complement‐activating Tg/anti‐Tg complexes, binding of IC to B cells, and the subsequent proliferation of B and T cell subsets. This represents a novel mechanism for the maintenance of autoimmune processes in AITD and links autoreactive T cell responses with the presence of autoantibodies.
Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells
Authors: Mariani Margherita , Lang Rosmarie , Binda Elisa , Panina‐Bordignon Paola , D'Ambrosio Daniele
Published: February 2004

Chemokines and their receptors play a pivotal role in controlling T cell trafficking in immunity and inflammation. Two chemokines, CCL17 and CCL22, activate the chemokine receptor CCR4, expressed on functionally distinct subsets of T cells: cutaneous leukocyte‐associated antigen (CLA)+ skin‐homing, T helper (Th) 2, and CD25+ T suppressor cells. Here, we compared the ability of CCL17 and CCL22 to promote CCR4 internalization as a mechanism of regulation of receptor function on human Th2 cells. We report that CCL22 is a potent and rapid inducer of CCR4 internalization, while CCL17 is not. CCR4 internalization does not require G protein coupling, while being dependent on lipid rafts integrity and clathrin‐coated pits functionality. Cell surface disappearance ofCCR4 is rapidly reversed upon removal of exogenous ligand by virtue of receptor recycling. CCR4 internalization leads to a loss of functional responsiveness, while recovery of surface expression leads to re‐acquisition of chemotactic sensitivity of Th2 cells. The differential CCR4 desensitization and internalization reported here and the distinct expression patterns of CCL17 and CCL22 observed in vivo suggest that while CCL17 may act first on CCR4 at the endothelial surface to promote vascular recognition, CCL22 could subsequently engage the receptor within the tissue microenvironmentto guide cellular localization.
Developmental status of CD4–CD8+ and CD4+CD8– thymocytes with medium expression of CD3
Authors: Sheard Michael A. , Liu Cunlan , Takahama Yousuke
Published: February 2004

In normal mice, more than 10% of thymocytes in the CD4+CD8– and CD4–CD8+ single‐positive (SP) subsets express a medium level of CD3 on the cell surface. However, the fate of CD3medium cells is unclear. The CD3medium SP subpopulations might contain (i) cells in an immature stage of the pathways leading to CD3high cells, (ii) cells in developmental pathways that do not lead to CD3high cells, or (iii) cells that have been negatively selected. We found that sorted CD3medium CD4+CD8– thymocytes from adult mice up‐regulated CD3 to high levels in reaggregation thymus organ culture. Unlike their CD3high counterparts, CD3medium CD4+CD8– thymocytes wereunable to undergo chemotaxis towards the chemokines CCL19 and CCL21. CD3medium thymocytes of both CD4+CD8– and CD4–CD8+ subsets were also considerably more responsive than CD3high SP cells to apoptotic signals induced in vitro by ligation of CD95 (Fas/APO‐1) or by dexamethasone. In both SP subsets, a higher frequency of thymocytes expressing forbidden Vβ+ T cell receptors reactive with endogenous mammary tumor virus superantigens was found in CD3medium subpopulations than in CD3high subpopulations.These findings argue that the CD3medium SP thymocyte subpopulations contain apoptosis‐susceptible precursor cells of CD3high SP cells and are subject to negatively selecting pressures.
Interleukin 10 regulates cell surface and soluble LIR‐2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro
Authors: Beinhauer Brigitte G. , McBride Jacqueline M. , Graf Philipp , Pursch Edith , Bongers Monique , Rogy Michael , Korthauer Ulf , de Vries Jan E. , Aversa Gregorio , Jung Thomas
Published: February 2004

Dendritic cells (DC) are unique in their ability to stimulate naive T cells to proliferate and to differentiate into effector T cells. DC, however, can also inhibit T cell activation and play a role in central and peripheral tolerance. IL‐10 has been shown to render DC tolerogenic by unknown mechanisms. Using a combined monoclonal antibody/retroviral expression cloning approach, we show here that the inhibitory receptor LIR‐2 (leukocyte immunoglobulin‐like receptor‐2, CD85d) is specifically up‐regulated by IL‐10 on maturing human DC. LPS‐stimulated, LIR‐2‐transfected DC inhibited the proliferation of T cells in autologous, as well as allogeneic culture systems in vitro. In addition, overexpression of LIR‐2 on resting T cells, which lack LIR‐2 expression, inhibited T cell proliferation induced by TCR activation. A novel soluble form of LIR‐2 was detected in culture supernatants of maturing DC. IL‐10 treatment of DC potently inhibited the production of soluble LIR‐2. Recombinant soluble LIR‐2 was able to completely restore the proliferation of T cells activated with LPS‐plus IL‐10‐treated DC. Thus, IL‐10 renders DC hypostimulatory by up‐regulating cell surface LIR‐2 and by inhibiting soluble LIR‐2 in vitro.
Dendritic cells generated in the presence of GM‐CSF plus IL‐15 prime potent CD8+ Tc1 responses in vivo
Authors: Pulendran Bali , Dillon Stephanie , Joseph Chryshanthi , Curiel Tyler , Banchereau Jacques , Mohamadzadeh Mansour
Published: February 2004

Dendritic cells (DC) comprise a system of professional antigen‐presenting cells, which induce the stimulation of very rare antigen‐specific naive T cells. DC progenitors can be stimulated to differentiate into immature DC by various growth factors, including GM‐CSF and IL‐4. Here we show that IL‐15, in combination with GM‐CSF, is a growth factor for murine DC. Murine bone marrow cells, depleted of T cells, B cells, I‐A+ cells and Gr‐1+ granulocytes, and cultured in the presence of GM‐CSF plus IL‐15 (IL‐15 DC), yielded DC expressing high levels of CD11c and MHC class II molecules, as well as CD11b. These cells expressed significant levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells efficiently. Interestingly, IL‐15 DC were farsuperior to DC generated with GM‐CSF plus IL‐4 in stimulating allogeneic CD8+ T cells in vitro. Consistent with this, IL‐15 DC induced much more potent antigen‐specific CD8+ T cell responses with high levels of Th1 cytokines in vivo, compared to DC generated with GM‐CSF plus IL‐4, or with GM‐CSF plus TGF‐β, or with GM‐CSF alone. Together, these data suggest that IL‐15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo. This suggests potential roles for these IL‐15 DC cells in the immunotherapy of tumors and infectious diseases.
Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II‐transgenic mice
Authors: Mangalam Ashutosh K. , Khare Meenakshi , Krco Christopher , Rodriguez Moses , David Chella
Published: February 2004

Multiple sclerosis (MS) is an immune‐mediated demyelinating disease of the CNS that is associated with HLA class II molecules HLA‐DR2, ‐DR3 and ‐DR4. Previously, it has been difficult to analyze the role of individual HLA molecules in disease pathogenesis due to heterogeneity of MHC genes, linkage disequilibrium, influence of non‐MHC genes and contribution of environment. To overcome some of these problems, we have generated HLA‐transgenic (tg) mice to investigate function and interaction of these molecules in disease pathogenesis. To investigate the role of individual HLA class IIgenes in immune responses to human proteolipid protein (PLP), a candidate autoantigen in MS, mice expressing HLA genes DR2, DR3, DR4 (DRB1*;0401 and DRB1*;0402), DQ6 and DQ8, lacking endogenous class II molecules were immunized with overlapping peptides of PLP. In all tg mice, the majority of the dominant T cell epitopes were clustered mainly to three region; amino acids 31–70, 91–120 and 178–228, of the PLP molecules. We also identified an encephalitogenic epitope PLP91–110 that induced clinical EAE in HLA‐DR3 tg mice. These tg mice had inflammatory infiltrates classically associated with EAE and showed a Th1 cytokine profile. This humanized mouse model of MS will be valuable in deciphering the role of HLA molecules and autoantigens in MS.
The neuronal protein Kidins220 localizes in a raft compartment at the leading edge of motile immature dendritic cells
Authors: Riol‐Blanco Lorena , Iglesias Teresa , Sánchez‐Sánchez Noelia , de la Rosa Gonzalo , Sánchez‐Ruiloba Lucía , Cabrera‐Poch Noemi , Torres Ana , Longo Isabel , García‐Bordas Julio , Longo Natividad , Tejedor Alberto , Sánchez‐Mateos Paloma , Rodríguez‐Fernández José Luis
Published: February 2004

Kidins220, a protein predominantly expressed in neural tissues, is the first physiological substrate for protein kinase D (PKD). We show that Kidins220 is expressed in monocyte‐derived and in peripheral blood immature dendritic cells (im DC). Immature DC (im DC) migrate onto extracellular matrices changing cyclically from a highly polarized morphology (monopolar (MP) stage) to a morphologically symmetrical shape (bipolar (BP) stage). Kidins220 was localized on membrane protrusions at the leading edge or on both poles in MP and BP cells, respectively. CD43, CD44, ICAM‐3 and DC‐SIGN,and signaling molecules PKD, Arp2/3 were found at the leading edge in MP or on both edges in BP cells, showing an intriguing parallelism between morphology and localization of molecular components on the poles of the motile DC. F‐actin co‐localized and it was necessary for Kidins220 localization on the membrane in MP and BP cells. Kidins220 was also found in a raft compartment. Disruption of rafts with methyl‐β‐cyclodextrin induced rounding of the cells, inhibition of motility and lost of Kidins220 polarization. Our results describe for the first time the molecular components of the polesof motile im DC and indicate that a novel neuronal protein may be an important component among these molecules.
Commentary: C‐type lectins on the macrophage cell surface – recent findings
Authors: Marshall Andrew S. J. , Gordon Siamon
Published: February 2004

Interest in the C‐type lectin family as a fundamental mediator of diverse immune interactions has grown exponentially in recent years, especially concerning members expressed on NK cells and their roles in anti‐viral and anti‐tumor immunity. For macrophages, however, collating the roles of the broad range of C‐type lectins expressed may be a more complex task. Analysis of the configuration of the C‐type lectin(‐like) domains among any other conserved modules reveals subfamilies of highly divergent structures. The identified ligands are likewise highly varied; however, most in vivo ligands are unknown and the significance of any recognized interactions is not well understood. In this commentary we review key features of C‐type lectin and lectin‐like receptor expression on macrophages and discuss recent data that sheds light on their varied functions. We aim to highlight the considerable body of novel/uncharacterized members of this receptor family and to place in context the initial description of CLECSF8, which is reported in this issue of the journal.

See accompanying article http://dx.doi.org/10.1002/eji.200324230
The mitochondrial phase of the glucocorticoid‐induced apoptotic response in thymocytes comprises sequential activation of adenine nucleotide transporter (ANT)‐independent and ANT‐dependent events
Authors: Sade Hadassah , Khandre Nagamani S. , Mathew M. K. , Sarin Apurva
Published: February 2004

In thymocytes, dexamethasone initiates cytochrome c‐dependent processing of caspase‐9 and the activation of caspase‐3 to trigger apoptotic damage. Using murine thymocytes or a thymocyte cell line WEHI 7.1, we show that this pathway is inhibited by dominant‐negative caspase‐9, the anti‐apoptotic protein Bcl‐2, or by blocking components of the mitochondrial permeability transition pore complex (PTPC). We use DIDS (dithiocyanatostilbene‐2,2‐disulfonic acid), a pharmacological modifier of VDAC (voltage‐dependent anion channel) function or ectopic expression of hexokinase‐II, to examinethe role of the VDAC – a mitochondrial outer membrane protein – in this apoptotic pathway. This approach implicated the VDAC in dexamethasone‐mediated cytochrome c release, processing of caspase‐9 and caspase‐3, the loss of mitochondrial transmembrane potential (Δ ψm), nuclear damage and cell lysis. Inhibiting the adenine nucleotide transporter (ANT), a protein on the mitochondrial inner membrane, also blocks dexamethasone‐induced apoptosis, but the ANT regulates caspase‐3 processing and nuclear damage but not the mitochondrial efflux of cytochrome c. Collectively, the data identifytwo separable, but connected events in dexamethasone‐induced mitochondrial damage in thymocytes. The first event is an increase in permeability of the mitochondrial outer membrane leading to VDAC‐regulated efflux of cytochrome c and initial processing of caspase‐9 followed by ANT‐dependent caspase‐3 processing and apoptotic damage to cells.
Mini‐review: Defense strategies and immunity‐related genes
Authors: Trowsdale John , Parham Peter
Published: February 2004

The immune system is of crucial importance in defense against infection. It has to cope with a large number of different pathogens that relentlessly develop new ways to avoid recognition or elimination. Yet most infections are cleared. Immune‐system genes must evolve to keep pace with increasingly sophisticated evasion by pathogens. In this article we examine features of human defense genes that reflect the demands imposed by such intense selection. Key examples are MHC and KIR genes, where features such as polygeny and polymorphism facilitate the comprehensive logistics needed to counteract infection.
Kinetics of Epoxy–Amine Curing Accompanied by the Formation of Liquid Crystalline Structure
Authors: Vyazovkin Sergey , Mititelu Alice , Sbirrazzuoli Nicolas
Published: February 2004

The curing of a mesomorphic epoxy has been studied by polarized light microscopy (PLM) and differential scanning calorimetry. PLM in combination with wide‐angle X‐ray diffraction proves the formation of a liquid crystalline (LC) structure. An advanced isoconversional method reveals that the formation of the LC structure is accompanied by a dramatic decrease in the effective activation from ∼60 to ∼10 kJ · mol−1. A kinetic model of the phenomenon has been discussed.

The dependence of the activation energy on the extent of conversion for isothermal curing of the diglycidyl ether of 4,4′‐dihydroxybiphenyl/2,6‐diaminopyridine (diamonds) and DGEBA/2,6‐diaminopyridine (circles) systems.

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The dependence of the activation energy on the extent of conversion for isothermal curing of the diglycidyl ether of 4,4′‐dihydroxybiphenyl/2,6‐diaminopyridine (diamonds) and DGEBA/2,6‐diaminopyridine (circles) systems.
Initiator‐Grafted Silica Particles for Controlled Free Radical Polymerization: Influence of the Initiator Structure on the Grafting Density
Authors: Parvole Julien , Laruelle Gaël , Guimon Claude , Francois Jeanne , Billon Laurent
Published: February 2004

A series of organic‐inorganic hybrid particles were synthesized by a self‐assembled layer of different initiators, immobilized on silica particles and used for controlled radical polymerization. We use three different initiator systems for atom‐transfer radical polymerization (ATRP), unimolecular nitroxide mediated polymerization (NMP), and bimolecular NMP, for the development of the hybrid inorganic/organic particles. After preliminary qualitative characterization by X‐ray spectroscopy (XPS) and Fourier‐transformed infrared (FT‐IR) measurements, the hybrid nanoparticles were studied by thermogravimetric analysis (TGA) to determine and discuss the initiator graft density in terms of steric hindrance.

The coupling agents employed for the various approaches used here: a) NMP1‐bimolecular system, b) NMP2‐unimolecular system, and c) ATRP.

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The coupling agents employed for the various approaches used here: a) NMP1‐bimolecular system, b) NMP2‐unimolecular system, and c) ATRP.
Polystyrene‐Clay Nanocomposites Prepared with Polymerizable Imidazolium Surfactants
Authors: Bottino Francesco A. , Fabbri Elena , Fragalà Ignazio L. , Malandrino Graziella , Orestano Alice , Pilati Francesco , Pollicino Antonino
Published: February 2004

Polystyrene/montmorillonite nanocomposites were prepared via in situ bulk polymerization. New imidazolium salts were used to modify montmorillonite obtaining an improvement in thermal stability in comparison with a montmorillonite modified with a standard alkylammonium cation. The synthesized cations facilitate the formation of partially exfoliated structures because of the presence in their structure of a polymerizable group. The polystyrene/montmorillonite nanocomposites were characterized by X‐ray diffraction, thermogravimetric analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

The new thermally stable, reactive surfactant imidazolium salts (C12, C16 and C18) used to organically modify montmorillonite in this study.

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The new thermally stable, reactive surfactant imidazolium salts (C12, C16 and C18) used to organically modify montmorillonite in this study.
Synthesis of Well‐Defined Telechelic Aromatic Polyamides by Chain‐Growth Polycondensation: Application to the Synthesis of Block Copolymers of Polyamide and Poly(tetrahydrofuran)
Authors: Sugi Ryuji , Yokoyama Akihiro , Yokozawa Tsutomu
Published: February 2004

Well‐defined telechelic‐type aromatic polyamides having a secondary amino group and a phenyl ester moiety at each chain end were prepared by the chain‐growth polycondensation of phenyl 4‐(octylamino)benzoate (1) with initiator 2 (N‐tert‐butoxycarbonylated 1), followed by deprotection of the N‐protecting group of the initiator unit. This polycondensation was applied to the synthesis of well‐defined di‐ and triblock copolymers of aromatic polyamides and poly(tetrahydrofuran) (poly(THF)) by the reaction of the terminal secondary amino group of the polyamide with the living cationic propagating group of poly(THF).

Block copolymers of polyamide and poly(tetrahydrofuran).

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Block copolymers of polyamide and poly(tetrahydrofuran).
Synthesis of Polymer Brushes Using Atom Transfer Radical Polymerization
Authors: Pyun Jeffrey , Kowalewski Tomasz , Matyjaszewski Krzysztof
Published: February 2004

Atom transfer radical polymerization (ATRP) is a robust method for the preparation of well‐defined (co)polymers. This process has also enabled the preparation of a wide range of polymer brushes where (co)polymers are covalently attached to either curved or flat surfaces. In this review, the general methodology for the synthesis of polymer brushes from flat surfaces, polymers and colloids is summarized focusing on reports using ATRP. Additionally, the morphology of ultrathin films from polymer brushes is discussed using atomic force microscopy (AFM) and other techniques to confirm the formation of nanoscale structure and organization.

Formation of polymer brushes by ATRP.

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Formation of polymer brushes by ATRP.
Synthesis and Characterization of Novel Biodegradable Copolymers of 5‐Benzyloxy‐1,3‐dioxan‐2‐one and Glycolide
Authors: Cheng Si‐Xue , Miao Zhi‐Mei , Wang Lian‐Sheng , Zhuo Ren‐Xi
Published: February 2004

A series of novel biodegradable random copolymers of 5‐benzyloxy‐1,3‐dioxan‐2‐one (5‐benzyloxy‐trimethylene carbonate, BTMC) and glycolide were synthesized by ring‐opening polymerization. The copolymers were characterized by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The incorporation of BTMC units into the copolymer chains results in good solubility of the polymers in common solvents. The in vitro degradation rate can be tailored by adjusting the composition of the copolymers.

The in vitro degradation of the homopolymers and poly(BTMC‐co‐GA) copolymers.

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The in vitro degradation of the homopolymers and poly(BTMC‐co‐GA) copolymers.
Exercise‐induced dystonia as a preceding symptom of familial Parkinson's disease
Authors: Bruno Michiko K. , Ravina Bernard , Garraux Gaetan , Hallett Mark , Ptacek Louis , Singleton Amanda , Johnson Janel , Singleton Andrew , Hanson Melissa , Considine Elaine , Gwinn‐Hardy Katrina
Published: February 2004

Paroxysmal exercise‐induced dystonia can occur with Parkinson's disease (PD), and in rare cases, this can also be the presenting symptom. We report on 2 second cousins (no known consanguinity) who presented with paroxysmal exercise‐induced dystonia who later developed clinical features of PD. Although autosomal recessive inheritance was suggested, and the dystonic features further suggest parkin as a possible cause, ssequencing for parkin mutations was negative and this family may represent a genetic variant of PD. Further genotype–phenotype studies in this and similar families may give clues to pre‐symptomatic symptoms in PD and may reflect a particular phenotype of interest for genetics studies in the future. © 2003 Movement Disorder Society
Parkinson's disease patients with bilateral subthalamic deep brain stimulation gain weight
Authors: Macia Frédéric , Perlemoine Caroline , Coman Irène , Guehl Dominique , Burbaud Pierre , Cuny Emmanuel , Gin Henri , Rigalleau Vincent , Tison François
Published: February 2004

Weight, body mass index (BMI) and energy expenditure/energy intake (EE/EI) was studied in 19 Parkinson's disease (PD) patients after subthalamic deep brain stimulation (STN‐DBS) versus 14 nonoperated ones. Operated patients had a significant weight gain (WG, + 9.7 ± 7 kg) and BMI increase (+ 4.7 kg/m2). The fat mass was higher after STN‐DBS. Resting EE (REE; offdrug/ON stimulation) was significantly decreased in STN‐DBS patients, while their daily energy expenditure (DEI) was not significantly different. A significant correlation was found among WG, BMI increase, and pre‐operative levodopa‐equivalent daily dose, their reduction after STN‐DBS, and the differential REE related to stimulation and the REE in the offdrug/OFF stimulation condition. In conclusion, STN‐DBS in PD induces a significant WG associated with a reduction in REE without DEI adjustment. © 2003 Movement Disorder Society
Normal dopaminergic and serotonergic metabolites in cerebrospinal fluid and blood of restless legs syndrome patients
Authors: Stiasny‐Kolster Karin , Möller J. Carsten , Zschocke Johannes , Bandmann Oliver , Cassel Werner , Oertel Wolfgang H. , Hoffmann Georg F.
Published: February 2004

Cerebrospinal fluid (CSF) and blood obtained from 22 untreated or scarcely treated patients with moderate to severe restless legs syndrome (RLS; mean age, 58.6 ± 13 years) and 11 control subjects (mean age, 56.6 ± 12.9 years) were investigated for biogenic amines between 6:00 and 8:00 PM. We did not find any significant differences in the CSF concentrations of homovanillic acid, 3‐ortho‐ methyl‐dopa, levodopa, 5‐hydroxytryptophan, 5‐hydroxyindoleacetic acid, tetrahydrobiopterin, dihydrobiopterin, 5‐methyltetrahydrofolate, and neopterin. In addition, serotonin in whole blood and plasma activity of aromatic amino acid decarboxylase were all normal. Our results suggest that dopaminergic and serotonergic release is not substantially affected in RLS. © 2003 Movement Disorder Society
Phenotypic characterization of DYT13 primary torsion dystonia
Authors: Bentivoglio Anna Rita , Ialongo Tamara , Contarino M. Fiorella , Valente Enza M. , Albanese Alberto
Published: February 2004

We describe the phenotype of DYT13 primary torsion dystonia (PTD) in a family first examined in 1994. A complete neurological evaluation was performed on all available family members: 8 individuals were definitely affected by dystonia. The family was re‐evaluated in March 2000: at that time, 3 more individuals had developed symptoms of dystonia. Inheritance of PTD was autosomal dominant, with affected individuals spanning three consecutive generations and male‐to‐male transmission. Age at onset ranged from 5 to 43 years. Onset occurred either in the craniocervical region or in upper limbs. Progression was mild, and the disease course was benign in most affected individuals; generalization occurred only in 2 cases. We did not find anticipation of age at onset or of disease severity through generations. Most subjects presented with jerky, myoclonic‐like dystonic movements of the neck or shoulders. DYT13‐PTD is an autosomal dominant disease, with incomplete penetrance (58%). Clinical presentation and age at onset were more variable than in DYT1‐PTD, and the neck was involved in most of those affected. Moreover, the individuals with generalised dystonia were not severely disabled and were able to lead independent lives. To date, this is the only family with DYT13‐PTD. © 2003 Movement Disorder Society
Clinical and genetic features of myoclonus–dystonia in 3 cases: A video presentation
Authors: Kock Norman , Kasten Meike , Schüle Birgitt , Hedrich Katja , Wiegers Karin , Kabakci Kemal , Hagenah Johann , Pramstaller Peter P. , Nitschke Matthias F. , Münchau Alexander , Sperner Jürgen , Klein Christine
Published: February 2004

Many cases of myoclonus–dystonia (M‐D) are caused by mutations in the ϵ‐sarcoglycan (SGCE) gene. We describe 3 children with a similar clinical picture of autosomal dominant M‐D and an SGCE mutation in only one of them, suggesting that M‐D is genetically heterogeneous. © 2003 Movement Disorder Society
Cerebrospinal fluid analysis for Whipple's disease in patients with progressive supranuclear palsy
Authors: Pezzella Francesca Romana , Paglia Maria Grazia , Colosimo Carlo
Published: February 2004

The clinical picture of neurological involvement in Whipple's disease (WD) may resemble progressive supranuclear palsy (PSP). We looked for WD pathogen DNA in the cerebrospinal fluid of 9 patients with a clinical diagnosis of PSP. The analysis was negative for all samples, showing that WD is not commonly involved in the aetiopathogenesis of PSP. © 2003 Movement Disorder Society
Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus
Authors: Hjort Niels , Østergaard Karen , Dupont Erik
Published: February 2004

Most Parkinson's patients complain about sleep problems. The subjective effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on nocturnal disabilities and sleep quality was elucidated by the recently established Parkinson's disease sleep scale (PDSS). The DBS‐treated group obtained significant improvement of motor function assessed by the Unified Parkinson's Disease Rating Scale. The mean total PDSS improved significantly after surgery whereas no change was found for the control group. Significant improvements of individual questions were obtained for overall sleep quality and motor symptoms whereas nocturia and daytime sleepiness did not change despite significant reduction of parkinsonian medication. © 2003 Movement Disorder Society
Diagnostic considerations in juvenile parkinsonism
Authors: Paviour Dominic C. , Surtees Robert A.H. , Lees Andrew J.
Published: February 2004

Juvenile parkinsonism (JP) describes patients in whom the clinical features of parkinsonism manifest before 21 years of age. Many reported cases that had a good response to levodopa have proved to have autosomal recessive juvenile parkinsonism (AR‐JP) due to mutations in the parkin gene. With the exception of parkin mutations and dopa‐responsive dystonia, most causes are associated with the presence of additional neurological signs, resulting from additional lesions outside of the basal ganglia. Lewy body pathology has only been reported in one case, suggesting that a juvenile form of idiopathic Parkinson's disease may be extremely rare. © 2003 Movement Disorder Society
Late‐life action tremor in a southern sea otter (enhydris lutris nereis)
Authors: Louis Elan D. , Murray Michael J. , Miller Melissa A. , Pullman Seth L. , Vonsattel Jean Paul G.
Published: February 2004

Although tremor is highly prevalent in human beings, there are few reports of tremor occurring in other mammals. Such tremor can further our insight into the mechanisms and anatomical basis of human tremor disorders. We report on a southern sea otter with a slowly progressive 6.5 to 8.5 Hz action tremor of late life that shared several clinical characteristics with essential tremor. The main pathological finding was in the cerebellum, where there was extensive vacuolation of Purkinje cells. © 2003 Movement Disorder Society
Complete mitochondrial DNA sequence analysis in a family with early‐onset dystonia and optic atrophy
Authors: Brown Michael D. , Hosseini Seyed , Steiner Israel , Wallace Douglas C. , Korn‐Lubetzki Isabelle
Published: February 2004

The combination of optic atrophy and dystonia has been etiologically associated with mitochondrial DNA (mtDNA) mutations. We report here on the complete mtDNA sequence from the proband of a consanguineous family exhibiting “mitochondrial‐like” optic atrophy and dystonia. A candidate tRNAGly mutation was identified that was unique to the family. However, the mutation was homoplasmic in both affected and unaffected family members and we were unable to demonstrate a biochemical defect in patient mitochondria. Hence, it is unlikely that a mtDNA mutation accounts for the phenotype in this family. © 2003 Movement Disorder Society
Inter‐rater reliability of the International Cooperative Ataxia Rating Scale (ICARS)
Authors: Storey Elsdon , Tuck Kate , Hester Robert , Hughes Andrew , Churchyard Andrew
Published: February 2004

We assessed the inter‐rater reliability of the 100‐point International Cooperative Ataxia Rating Scale (ICARS). Three neurologists independently rated videotaped ICARS examinations of 22 subjects with genetically determined ataxias (spinocerebellar ataxia [SCA] Type 1 in 11; SCA Type 2 in 1; Friedreich's ataxia in 10) and 4 controls. Scores on live ICARS assessment had ranged from 0 to 7 for controls and 11 to 74 for ataxic subjects (clinically very mildly affected to wheelchair‐bound). Inter‐rater correlation was very high for the total score (Kendall's ω 0.994, 95% confidence interval, 0.988–0.997), and high to very high for each component subscore (0.791 for speech to 0.994 for posture/gait). All correlations were significant at P < 0.00001. The ICARS exhibits very high inter‐rater reliability even without prior observer standardisation and is sensitive to a range of ataxia severities from very mild to severe. © 2003 Movement Disorder Society
Familial cortical tremor with epilepsy and cerebellar pathological findings
Authors: van Rootselaar Anne‐Fleur , Aronica Eleonora , Jansen Steur Ernst N.H. , Rozemuller‐Kwakkel Johanna M. , de Vos Rob A.I. , Tijssen Marina A.J.
Published: February 2004

The clinical and neuropathological findings in a patient with familial cortical tremor with epilepsy (FCTE) are described. Clinically, the patient showed cortical myoclonus, tremor, and generalized seizures. Pathological investigation showed cerebellar degeneration and somal sprouting and loss of dendritic tree in Purkinje cells. Striking similarities were found in diseases caused by channelopathies such as spinocerebellar ataxia subtype 6. © 2003 Movement Disorder Society
Development of quality of care indicators for Parkinson's disease
Authors: Cheng Eric M. , Siderowf Andrew , Swarztrauber Kari , Eisa Mahmood , Lee Martin , Vickrey Barbara G.
Published: February 2004

Parkinson's disease (PD) is a major cause of disability. To date, there have been no large‐scale efforts to measure the quality of PD care because of a lack of quality indicators for conducting an explicit review of PD care processes. We present a set of quality indicators for PD care. Based on a structured review of the medical literature, 79 potential indicators were drafted. Through a two‐round modified Delphi process, an expert panel of seven movement disorders specialists rated each indicator on criteria of validity, feasibility, impact on outcomes, room for improvement, and overall utility. Seventy‐one quality indicators met validity and feasibility thresholds. Applying thresholds for impact on outcomes, room for improvement, and overall utility, a subset of 29 indicators was identified, spanning dopaminergic therapy, assessment of functional status, assessment and treatment of depression, coordination of care, and medication use. Multivariable analysis showed that overall utility ratings were driven by validity and impact on outcomes (P < 0.01). An expert panel can reach consensus on a set of highly rated quality indicators for PD care, which can be used to assess quality of PD care and guide the design of quality improvement projects. © 2003 Movement Disorder Society
Quantification of focal dystonia in pianists using scale analysis
Authors: Jabusch Hans‐Christian , Vauth Henning , Altenmüller Eckart
Published: February 2004

Focal dystonia in pianists is a task‐specific movement disorder that causes loss of pianistic skills and provokes irregularities in playing. So far, no method has been available for objective quantification of the disorder. Eight professional pianists with focal dystonia and eight healthy professional pianists matched by age, gender, and handedness were examined, using a newly developed MIDI‐based Scale Analysis as well as the Arm Dystonia Disability Scale (ADDS). Key velocities and timing parameters were analyzed. In 5 pianists with dystonia, follow‐up examinations were carried out after treatment with botulinum toxin‐A. In affected hands, significantly higher mean standard deviations of timing parameters were seen compared with healthy reference hands. After treatment with botulinum toxin‐A, significant improvements in performance parameters were monitored by Scale Analysis. Mean standard deviations of inter‐onset intervals correlated with ADDS scores. We conclude that Scale Analysis is an effective and precise tool for quantification of focal dystonia in pianists and provides fine resolution. It is independent of rating methods and allows reliable follow‐up examinations during treatment. © 2003 Movement Disorder Society
Accuracy of clinical diagnosis of progressive supranuclear palsy
Authors: Osaki Y. , Ben‐Shlomo Y. , Lees A. J. , Daniel S. E. , Colosimo C. , Wenning G. , Quinn N.
Published: February 2004

We assessed the accuracy of clinical diagnosis of progressive supranuclear palsy (PSP, Steele‐Richardson‐Olszewski disease) and the validity of existing sets of clinical diagnostic criteria for PSP (see Appendix) using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Diagnosis of PSP was made by 40 different physicians, and 60 cases clinically diagnosed as PSP when last assessed in life were studied. In 47 cases (78%), the diagnosis of PSP was confirmed pathologically. False‐positive diagnoses included Parkinson's disease with significant additional cortical Lewy body (n = 3) or Alzheimer (n = 1) pathology, multiple system atrophy (n = 4), and corticobasal degeneration, Pick's disease, motor neurone disease, cerebrovascular disease, and a sporadic case of frontotemporal dementia and parkinsonism linked to chromosome 17 (1 case each). Most cases of PSP were diagnosed accurately by neurologists at the final assessment. Although application of National Institute of Neurological Disorders and the Society for PSP possible category marginally improved the accuracy of initial clinical diagnosis, none of the existing operational criteria could significantly improve accuracy of the final clinical diagnosis. © 2003 Movement Disorder Society
Alteration in α‐synuclein mRNA expression in Parkinson's disease
Authors: Kingsbury Ann E. , Daniel Susan E. , Sangha Hardev , Eisen Sarah , Lees Andrew J. , Foster Oliver J.F.
Published: February 2004

The presynaptic protein α‐synuclein is considered to play an important role in the pathophysiology of Parkinson's disease (PD). Point mutations in the α‐synuclein gene have been demonstrated in familial PD and α‐synuclein is a major component of Lewy bodies, the pathological hallmark of the sporadic disease. It is not clear whether abnormal accumulation of α‐synuclein is the result of abnormal levels of expression of the gene in neurodegenerative conditions. Expression of α‐synuclein mRNA was therefore studied in control and PD brain using semiquantitative in situ hybridization. α‐synuclein was expressed widely and hybridization signal was seen in most cortical regions, hippocampus, cerebellum, and brain stem. There was little mRNA in the striatum and no hybridization signal was detected in glia. High levels of α‐synuclein mRNA expression in neurons did not seem to be a marker for Lewy body formation. Abundant signal was seen both in regions in which Lewy body deposition occurs commonly in idiopathic PD (PD), such as substantia nigra and frontal and temporal cortex, as well as in less susceptible regions, e.g. visual cortex. Quantitative comparison of mRNA expression in regions of predilection for Lewy body formation showed that mRNA expression was reduced significantly in melanized substantia nigra neurons and frontal cortex neurons in Parkinson's disease. In substantia nigra neurons there seemed to be a negative correlation between cellular mRNA expression and disease duration. These findings are in broad agreement with other studies of the expression of α‐synuclein mRNA in human brain and suggest that Lewy body formation is unlikely to be the result of overexpression of α‐synuclein. © 2003 Movement Disorder Society
Utilization and perceived effectiveness of complementary and alternative medicine in patients with dystonia
Authors: Junker J. , Oberwittler C. , Jackson D. , Berger Klaus
Published: February 2004

The use of complementary and alternative medicine (CAM) is increasing worldwide, especially by patients with chronic diseases. To date, no data are available about utilization and perceived effectiveness of CAM in patients with dystonia. A questionnaire survey on utilization and costs of CAM was completed by 180 members of the German Dystonia Society, a patient advocate group. In total, 131 dystonia patients (73%) were current or former users of CAM, 55 patients used CAM in addition to botulinum toxin A injections, and 86 patients had experience with three or more CAM methods. The options used most widely were acupuncture (56%), relaxation techniques (44%), homeopathy (27%), and massages (26%). Among users of specific CAM methods, breathing therapy, Feldenkrais, massages, and relaxation techniques were perceived as most effective. On average, patients spent
€1,513 on CAM without reimbursement. There was no correlation between costs and perceived effectiveness of different methods. In line with other studies on chronically ill patients, our results show that dystonia patients frequently utilize CAM methods, often in addition to conventional treatment. There is a growing need to evaluate scientifically the effect of CAM methods on symptom severity and quality of life in dystonia, to prevent utilization of costly and ineffective CAM treatments. © 2003 Movement Disorder Society
Anomalies of asymmetry of clinical signs in parkinsonism
Authors: Toth Cory , Rajput Michelle , Rajput Ali H.
Published: February 2004

Parkinson's disease (PD) is characterized by a minimum of two of three features: tremor, rigidity, and bradykinesia. Asymmetry of these features is often considered to support a diagnosis of PD in contrast to other parkinsonian syndromes. All major manifestations of PD are often more pronounced on the side first manifesting features of PD. Significant dissociation of features on the contralateral side, along with other variants of presentation involving the contralateral side, are rarely observed. To determine the frequency and significance of unusual asymmetry in parkinsonism, we retrospectively examined 613 patients clinically diagnosed as idiopathic PD for presence of unusual asymmetries of clinical features. Three groups of patients with unusual asymmetrical clinical findings were identified. Group 1 comprised 10 patients followed for an average of 6 years presenting with rest tremor most prominent in one lower limb and contralateral upper limb. Group 2 comprised 24 patients followed for an average of 5.5 years with action tremor most prominent on the side contralateral to the side of most prominent rest tremor. Group 3 comprised 33 patients followed for an average of 10 years who had parkinsonian signs of greatest severity on one side but subsequently, over an average of 5.4 years, became gradually more prominent on the opposite side. In Group 3, 15 of 33 patients (45%) demonstrated evolution to a rigid form of parkinsonism with disappearance of rest tremor over an average of 7.1 years after presentation. A small percentage (11%) of Parkinson's patients in our clinic demonstrated anomalous asymmetrical clinical findings, which indicates that (1) the disease process may begin in different topographic sites on each side; (2) rest tremor and action tremor may have different anatomical bases; (3) the disease process may progress at different rates on different sides; and (4) tremor becomes less pronounced with progression of disease in some patients with Parkinsonism. © 2003 Movement Disorder Society
An immersed finite element space and its approximation capability
Authors: Li Z. , Lin T. , Lin Y. , Rogers R. C.
Published: February 2004

This article discusses an immersed finite element (IFE) space introduced for solving a second‐order elliptic boundary value problem with discontinuous coefficients (interface problem). The IFE space is nonconforming and its partition can be independent of the interface. The error estimates for the interpolation of a function in the usual Sobolev space indicate that this IFE space has an approximation capability similar to that of the standard conforming linear finite element space based on body‐fit partitions. Numerical examples of the related finite element method based on this IFE space are provided. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 20: 338–367, 2004
Application of a Mickens finite‐difference scheme to the cylindrical Bratu‐Gelfand problem
Authors: Buckmire Ron
Published: February 2004

The boundary value problem Δu + λeu = 0 where u = 0 on the boundary is often referred to as “the Bratu problem.” The Bratu problem with cylindrical radial operators, also known as the cylindrical Bratu‐Gelfand problem, is considered here. It is a nonlinear eigenvalue problem with two known bifurcated solutions for λ < λc, no solutions for λ > λc and a unique solution when λ = λc. Numerical solutions to the Bratu‐Gelfand problem at the critical value of λc = 2 are computed using nonstandard finite‐difference schemes known as Mickens finite differences. Comparison of numerical results obtained by solving the Bratu‐Gelfand problem using a Mickens discretization with results obtained using standard finite differences for λ < 2 are given, which illustrate the superiority of the nonstandard scheme. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 20: 327–337, 2004