bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen‐specific production of interleukin (IL)‐13 and IL‐5 cooperate to mediate IL‐4Rα‐independent airway hyperreactivity
Authors: Webb Dianne C. , Mahalingam Surendran , Cai Yeping , Matthaei Klaus I. , Donaldson Debra D. , Foster Paul S.
Published: November 2003

The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL‐13. Analyses of the receptor components employed by IL‐13 have shown that delivery of this cytokine to the airways of naive IL‐4Rα gene targeted (IL‐4Rα–/–) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL‐13‐mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin‐sensitized IL‐4Rα–/– mice and that these responses can be inhibited by the IL‐13 antagonist sIL‐13Rα2Fc. Therefore, antigen stimulation induces an IL‐13‐regulated response that is independent of IL‐4Rα. To determine the role of IL‐5 and eosinophils in the development of disease in antigen‐exposed IL‐4Rα–/– mice, pulmonary allergy was examined in mice deficient in both factors. IL‐4Rα/IL‐5–/– mice were significantly defective in their ability to produce IL‐13 and failed to develop AHR, suggesting that IL‐5 indirectly regulates AHR in allergic IL‐4Rα–/– mice by an IL‐13‐dependent mechanism. Collectively, these results demonstrate that IL‐13‐dependent processes regulating the development of AHR and T helper bias persist in the inthe lungs of allergic IL‐4Rα–/– mice.
B cell defects in SLP65/BLNK‐deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling
Authors: Gerlach Judith , Ghosh Snigdha , Jumaa Hassan , Reth Michael , Wienands Jürgen , Chan Andrew C. , Nitschke Lars
Published: November 2003

CD22 is an inhibitory coreceptor for B cell receptor (BCR) signaling. The inhibition is most likely mediated by activation of SHP‐1. We found that SLP65/BLNK reaches maximal tyrosine‐phosphorylation at earlier time points in CD22–/– than in wild type B cells upon BCR cross‐linking, suggesting that SLP65/BLNK is a substrate of SHP‐1. However, in contrast to the defective Ca2+ mobilization of SLP65/BLNK–/– B cells, there was a clear Ca2+ response in SLP65/BLNK×CD22 double‐deficient B cells. This implies that SLP65/BLNK is not the sole target of SHP‐1 in the regulation of the Ca2+ signaling strength. While SLP65–/– mice show several blocks of B cell differentiation, in SLP65/BLNK×CD22 double‐deficient mice the maturationblock of B cells in the spleen was partially rescued. However, the proliferative responses of B cells from both SLP65/BLNK–/– and double‐deficient mice were defective after IgM‐ or CD40‐stimulation. These results show that SLP65/BLNK is not absolutely essential for Ca2+ induction in B cells, because the deficiency of this adapter can be by‐passed by the additional deletion of an inhibitory receptor. Furthermore, these experiments suggest that B cell maturation in the spleen is directly dependent on the strength of BCR‐derived Ca2+ signals.
Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes
Authors: Leslie Robert Graham Quinton , Prodinger Wolfgang Maria , Nielsen Claus Henrik
Published: November 2003

The C3b‐binding receptor, CR1/CD35, supports CR2/CD21‐mediated activation of complement by human B lymphocytes, possibly by associating with CR2 to promote or stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP convertase, C3i‐Bb. To evaluate this hypothesis, we examined the uptake kinetics and binding equilibria for C3i dimer interaction with human blood cells in the absence and presence of CR1‐ and CR2‐blocking mAb. C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2. The forward rate constants (k1) for CR1 and CR2, operating independently, differed ca. 9‐fold (k1=193±9.4 and 22.2±6.0×103 M–1s–1, respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13‐fold over the C3i concentration range examined. The maximum association constant (Ka, max=109±27.2×107 l/mole) was ca. 9‐ and 6‐fold greater, respectively, than those for CR1 or CR2 acting alone (Ka=13.2±5.3 and 18.5±3.5×107 l/mole). The high avidity of the CR1‐CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2, respectively.
Efficient generation and expansion of antigen‐specific CD4+ T cells by recombinant influenza viruses
Authors: Nimmerjahn Falk , Kobelt Dieter , Steinkasserer Alexander , Menke Annette , Hobom Gerd , Behrends Uta , Bornkamm Georg W. , Mautner Josef
Published: November 2003

Adoptive transfer of in vitro generated antigen‐specific T cells has been successfully used to treat viral infections in immunodeficient patients. Therefore, methods for the rapid in vitro expansion of antigen‐specific T cells are needed. Influenza virus efficiently infects dendritic cells, and peptides derived from viral proteins are processed and presented to CD8+ cytotoxic T cells. However, both, CD4+ and CD8+ T cells are necessary for the efficient control of viral infections, and it is becoming increasingly clear that a T helper cell response is very important for the maintenance and strength of the immune response. Here we show that recombinant influenza virus efficiently infects a wide range of professional antigen‐presenting cells and does not interfere with antigen presentation pathways. Using T cell clones for three different MHC class II‐restricted antigens we demonstrate that peptides derived from these antigens are efficiently presented on MHC class II molecules. Importantly, it was possible to generate and expand antigen‐specific CD4+ T cells following in vitro infection of professional antigen‐presenting cells with recombinant influenza virus. These findings support the notion that recombinant influenza virus is a valuable tool for the expansion of antigen‐specific CD4+ T cells in vitro.
Diabetogenic T cells are primed both in pancreatic and gut‐associated lymph nodes in NOD mice
Authors: Jaakkola Ilkka , Jalkanen Sirpa , Hänninen Arno
Published: November 2003

Activation of an islet‐specific immune response is an early yet essential step in autoimmune diabetes. The immune cells and antigen(s) involved in this early step and its anatomical site remain incompletely understood. To directly evaluate the site where islet‐specific and diabetogenic lymphocytes are activated, we isolated lymphocytes from spleen and from pancreas‐draining, gut‐associated and subcutaneous lymph nodes of diabetic NOD mice and of young NOD mice, and transferred these into NOD scid/scid recipients devoid of endogenous islet‐specific immune responses themselves. Although spleen lymphocytes from diabetic NOD mice induced diabetes more rapidly than lymphocytes from any other lymphoid tissue, spleen lymphocytes from young NOD donors were not superior to other lymphocytes from the same donors. At a donor‐age of 6 weeks, the most‐diabetogenic lymphocytes were found in pancreas‐draining lymph node whereas gut‐associated lymph nodes and the spleen were sources of intermediate diabetogenic activity. Lymphocytes from peripheral lymph nodes were only weakly diabetogenic at this age, and also remained the least efficient later. Surprisingly, lymphocytes isolatedeven from 3‐week‐old NOD mice had diabetogenic potential. However, such cells were almost exclusively found in gut‐associated lymph nodes. This suggests that initial priming of diabetogenic cells takes place in the gut whereas pancreas‐draining lymph nodes may serve as the site of amplification of the autoimmune response.
Dendritic cell‐derived IL‐15 controls the induction of CD8 T cell immune responses
Authors: Rückert René , Brandt Katja , Bulanova Elena , Mirghomizadeh Farhad , Paus Ralf , Bulfone‐Paus Silvia
Published: November 2003

The development and the differentiation of CD8+ T cells are dependent on IL‐15. Here, we have studied the source and mechanism of how IL‐15 modulates CD8+ T cell‐mediated Th1immune responses by employing two delayed‐type hypersensitivity (DTH) models. IL‐15‐deficient (IL‐15–/–) mice or mice treated with soluble IL‐15Rα as an IL‐15 antagonist showed significantly reduced CD8+ T cell‐dependent DTH responses, while activation of CD4+ T cell and B cell functions remained unaffected. Injection of antigen‐labeled dendritic cells (DC) fromIL‐15+/+, IL‐15–/– or IL‐15Rα–/– mice revealed that DC‐derived IL‐15 is an absolute requirement for the initiation of DTH response. The re‐establishment of the interaction of IL‐15 with the IL‐15Rα by incubating IL‐15–/– DC with IL‐15 completely restored the capacity to prime T cells for DTH induction in vivo. Moreover, IL‐15 also enhanced secretion of pro‐inflammatory cytokines by DC and triggered in vitro CD8+ T cell proliferation and IL‐2 release. Taken together, the data suggest that an autocrine IL‐15/IL‐15Rα signaling loop in DC is essential for inducing CD8+‐dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeuticmodulation of clinically relevant DTH reactions.
Boron Clusters − A New Entity for DNA‐Oligonucleotide Modification
Authors: Lesnikowski Zbigniew J.
Published: November 2003

The carboranyl cluster is a new and versatile modifying entity for nucleotides and nucleic acids. Three types of carboranyl (−C2B10H11) group‐containing DNA‐oligonucleotides are described: (1) CBMP‐oligonucleotides, consisting of the carborane cage within an internucleotide linkage; (2) CDU‐oligonucleotides, containing the carborane cage attached to a nucleobase; and (3) 2′‐CBM‐oligonucleotides, with the carborane cage linked to a sugar residue at the 2′ position. The method of synthesis and the physicochemical and biochemical features of these novel modifications are discussed, together with structure−property relationships. The carboranyl cluster‐containing oligonucleotides form a crossover between (carba)borane chemistry and molecular biology. They are potentially useful as antisense agents for antisense oligonucleotide therapy (AOT) and boron carriers for boron neutron capture therapy (BNCT). The chemistry of carborane‐modified nucleic acids has implications beyond BNCT and AOT. Owing to the unique properties of carborane clusters they have potential for further development as molecular probes for molecular medical diagnostics and bioinorganic material for emerging technologies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Efficient Solution‐Phase Parallel Synthesis of 4‐Substituted N‐Protected Piperidines
Authors: Wang Xiaoyang , Kauppi Anna M. , Olsson Roger , Almqvist Fredrik
Published: November 2003

Practical conditions for the synthesis of 4‐substituted N‐protected piperidines through CuCN·2LiBr‐catalyzed organozinc additions to 1‐acylpyridinium salts and subsequent hydrogen‐transfer hydrogenation have been established. The reaction sequence is performed at room temperature and provides 4‐substituted N‐protected piperidines in excellent overall yields without the isolation of intermediate dihydropyridines. In those cases in which the organozinc addition results in mixtures of 2‐ and 4‐substituted dihydropyridines, the 2‐substituted isomers are efficiently scavenged with maleic anhydride and subsequently removed by a mild extractive workup with NaHCO3 (sat.). The N‐acyl group can conveniently be exchanged from N‐phenoxycarbonyl to N‐tBoc, thus allowing orthogonal deprotection strategies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Synthesis of Two Furan‐Based Analogues of the α′,β′‐Epoxy Ketone Proteasome Inhibitor Eponemycin
Authors: Bennacer Bibia , Trubuil Dominique , Rivalle Christian , Grierson David S.
Published: November 2003

Myers’s methodology for enantioselective amino acid synthesis was employed to prepare the N‐Boc didehydroleucine amide derivative 15 and to effect its conversion into the acylfuran intermediate 17. Coupling of 19 (R = H) with N‐(isooctanoyl)serine provided the furan‐based analogue 4 of eponemycin (de = 96 %), a peptide epoxide with potent cytotoxic and anti‐angiogenesis properties. In an identical fashion the corresponding unsaturated analogue 5 of eponemycin was prepared (de = 48 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003
A Novel Route to Chiral trans‐6‐Alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines by Allylation of Chiral Imines and Ring‐Closing Metathesis − Total Synthesis of (−)‐3‐epi‐Deoxoprosopinine
Authors: Felpin François‐Xavier , Boubekeur Kamal , Lebreton Jacques
Published: November 2003

A novel route to enantiomerically pure trans‐6‐alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines is reported in five steps from Garner’s aldehyde with overall yields higher than 35 %. This strategy is based on the allylation of chiral imino alcohols formed in situ followed by a ring‐closing metathesis. This new method was used for the first total synthesis of (−)‐3‐epi‐deoxoprosopinine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Aza‐MIRC Reactions of Sulfonyl‐Activated Hydroxycarbamates with α,β‐Difunctionalised Acrylates
Authors: Fioravanti Stefania , Morreale Alberto , Pellacani Lucio , Tardella Paolo A.
Published: November 2003

Highly functionalised aziridines are readily obtained in high yields (up to 95%) under mild conditions from the reaction of trisubstituted olefins bearing different groups with nosyloxycarbamates in the presence of calcium oxide. We propose a possible explanation for the different reactivities observed between these olefins and the aminating agents. Reagent‐controlled stereoselective amination reactions led to the expected products with high conversions and purities. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Stripping Voltammetric Determination of Zirconium with Complexing Preconcentration of Zirconium(IV) at a Morin‐Modified Carbon Paste Electrode
Authors: Liu Shumei , Li Junan , Mao Xun
Published: November 2003

A sensitive, selective and economic stripping voltammetry is described for the determination of trace amounts of zirconium at a morin‐modified carbon paste electrode (morin‐MCPE). Zirconium(IV) can be preconcentrated on the surface of the morin‐MCPE due to forming the Zr(IV)–morin complex. The complex produces two second‐order derivative anodic peaks at 0.69 V (vs. SCE) and 0.75 V when linear‐scanning from 0.0 to 1.0 V. The optimum analytical conditions are: 2.2 mol L−1 HCl, 0.0 V accummulation potential, 90 s accummulation time, 250 mV s−1 scan rate. A linear relationships between the peak currents at 0.75 V and the Zr(IV) concentration are in the range of 2.0×10−8 to 3.0×10−6 mol L−1. The detection limit is 1.0×10−8 mol L−1 (S/N=3) for 120 s accumulation. The RSD for determination of 4.0×10−7 mol L−1 Zr(IV) is 4.8% (n=8). The proposed method has been applied to determine zirconium in ore samples, unnecessarily extracted.
Enantioselective Artificial Receptors Formed by the Spreader‐Bar Technique
Authors: Prodromidis Mamas I. , Hirsch Thomas , Mirsky Vladimir M. , Wolfbeis Otto S.
Published: November 2003

Chiroselective binding sites have been created on thin gold films by application of the spreader‐bar approach. Impedometric techniques and surface plasmon resonance were applied to detect binding. (R)‐(+)‐1,1′‐Binaphthyl‐2,2′‐diol (R‐BNOH) and (S)‐(−)‐1,1′‐binaphthyl‐2,2′‐diol (S‐BNOH) were used as model analytes. The artificial receptors were prepared by co‐adsorption of 16‐mercaptohexadecane (matrix) with a thiol‐modified chiral selector (template). The conjugates of D,L‐thioctic acid and (R)‐(+)‐ or (S)‐(−)‐1,1′‐binaphthyl‐2,2′‐diamine were used as templates. Different concentration ratios of the matrix and template were tested. No chiral selectivity of surfaces formed by either the matrix or the template alone was observed. The use of alkylthiols shorter than 16‐mercaptohexadecane led to the formation of surfaces with no chiral selectivity. The gold electrodes coated by the spreader‐bar technique displayed an enantioselectivity of up to 4.76 or up to 2.55 as measured by the capacitive and SPR methods, respectively.
A comparative study of volatile constituents of two Helichrysum italicum (Roth) Guss. Don Fil subspecies growing in Corsica (France), Tuscany and Sardinia (Italy)
Authors: Bianchini Ange , Tomi Pierre , Bernardini Antoine Francois , Morelli Ivano , Flamini Guido , Cioni Pier Luigi , Usaï Marianna , Marchetti Mauro
Published: November 2003

The essential oils obtained by water distillation from the aerial parts of two Helichrysum italicum ssp. growing in Corsica (France), Tuscany and Sardinia (Italy) were analysed by GC–RI and GC–MS. The essential oils prepared from Corsican and Tuscan Helichrysum italicum subsp. italicum exhibited two different compositions. Corsican oils were characterized by the pre‐eminence of oxygenated compounds: neryl acetate (major compound), neryl propionate, nerol, acyclic ketones and β‐diketones. Conversely, Tuscan oils were found to exhibit higher contents of hydrocarbons (α‐pinene, β‐caryophyllene, α‐ and β‐selinenes). The comparison of essential oils hydrodistilled from Corsican and Sardinian Helichrysum italicum subsp. microphyllum showed almost similar chemical compositions. The main constituents were: neryl acetate, nerol, neryl propionate, linalool, eudesm‐5‐en‐11‐ol and γ‐curcumene. Copyright © 2003 John Wiley & Sons, Ltd.
Composition of the essential oil of Ballota undulata, B. nigra ssp. foetida and B. saxatilis
Authors: Bader Ammar , Caponi Chiara , Cioni Pier Luigi , Flamini Guido , Ivano Morelli
Published: November 2003

The essential oil composition of Ballota nigra ssp. foetida, B. undulata and B. saxatilis, collected during the ﬂowering phase in Amman (Jordan), Naur (Jordan) and Pisa (Italy) respectively, was investigated. The chemical composition of the essential oil of B. nigra and B. undulata shows some similarities: monoterpenes are little represented, while sesquiterpenes are present in large amounts. In both cases germacrene D is the main compound. B. saxatilis essential oil is quite different from B. nigra and B. undulata ones: sesquiterpenes are still the main class of compounds but monoterpenes are much more represented; moreover, in this case the main compound is the oxygenated monoterpene, linalool. Copyright © 2003 John Wiley & Sons, Ltd.
Characteristic odour components of Citrus sp. (Kiyookadaidai) cold‐pressed peel oil
Authors: Minh Tu N. T. , Onishi Y. , Choi H. S. , Kondo Y. , Ukeda H. , Sawamura M.
Published: November 2003

The volatile components of Citrus sp. (Kiyookadaidai) cold‐pressed peel oil were investigated by chemical and sensory analyses. Monoterpene hydrocarbons were abundant, accounting for more than 90.2% of the total content. Myrcene was determined to be the predominant monoterpene hydrocarbon (62.4%), rather than limonene, which is usually reported as most abundant in citrus cold‐pressed oils. The weight percentages of alcohols, aldehydes and esters were >1.0%, >0.8% and >0.8%, respectively. Forty‐seven aroma‐active compounds were detected in Kiyookadaidai oil using GC–O and AEDA. Myrcene, (Z)‐ocimene and α‐bergamotene were the odour‐characteristic compounds, creating a Kiyookadaidai‐like odour. A model solution prepared from one certain con‐centration of myrcene, limonene and (Z)‐ocimene yielded the refreshing and characteristically green aroma of Kiyookadaidai cold‐pressed oil. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of metabolites and disposition of tertiary amyl methyl ether in male F344 rats following inhalation exposure
Authors: Sumner Susan C. J. , Asgharian Bahman , Moore Timothy A. , Parkinson Horace D. , Bobbitt Carol M. , Fennell Timothy R.
Published: November 2003

Tertiary amyl methyl ether (TAME) is a fuel additive used to reduce carbon monoxide in automobile emissions. Because of the potential for human exposure, this study was conducted to develop methods for the characterization and quantitation of metabolites in expired air and excreta of rats exposed to a mixture of [13C]‐ and [14C]TAME ([2,3,4‐13C]‐ and [2‐14C]2‐methoxy‐2‐methylbutane). The distribution of TAME in rats was determined following inhalation exposure, and TAME‐derived metabolites were characterized in expired air and urine. Male rats were exposed for 6 h via nose‐only inhalation to 2500 ppm [14C/13C]TAME, and expired air, urine and feces were collected for up to 7 days. Over 95% of the total recovered radioactivity was excreted by 48 h after exposure. Recovered radioactivity was expired as organic volatiles (44%) and 14CO2 (3%) and excreted in urine (51%) and feces (1%). Both TAME and its metabolite tertiary amyl alcohol (TAA) accounted for ≥90% of the radiolabel in expired air 0–8 h following exposure termination. Three major urinary metabolites of TAME were identiﬁed: (1) a direct glucuronide conjugate of TAA; (2) a product of oxidation at the methylene carbon of TAA (2,3‐dihydroxy‐2‐methylbutane); (3) a glucuronide conjugate of metabolite 2. Metabolite 1 accounted for most of the TAME‐derived metabolites excreted 0–8 h following exposure termination. Further metabolic products of TAA (metabolites 2 and 3) accounted for most of the excreted TAME‐derived metabolites at later time points. Copyright © 2003 John Wiley & Sons, Ltd.
Radiosynthesis of [N‐methyl‐11C]methylene blue
Authors: Schweiger Lutz , Craib Stuart , Welch Andrew , Sharp Peter
Published: November 2003

In this paper we present the radiochemical synthesis of the novel compound [N‐methyl‐11C]methylene blue. The synthesis of [N‐methyl‐11C]methylene blue was accomplished by means of 11C‐methylation of commercially available Azure B using [11C]methyl trifluoromethanesulfonate ([11C]methyl triflate). Following purification [N‐methyl‐11C]methylene blue was obtained with a radiochemical purity greater than 97% in a 4–6% decay corrected radiochemical yield. The synthesis was completed in an average of 35 min following the end of bombardment. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis of NCA [carbonyl‐11C]amides by direct reaction of in situ generated [11C]carboxymagnesium halides with amines under microwave‐enhanced conditions
Authors: Lu Shui‐Yu , Hong Jinsoo , Pike Victor W.
Published: November 2003

No‐carrier‐added (NCA) aromatic and aliphatic [carbonyl‐11C]amides were rapidly (<5 min) synthesized in one pot in useful radiochemical yields (20–65%, decay‐corrected) by directly coupling amines with NCA [11C]carboxyhyphenmagnesium halides generated in situ from Grignard reagents and cyclotron‐produced [11C]carbon dioxide. In this system cyclohexylcarboxymagnesium chloride (1b) is more reactive than 4‐fluorophenylcarboxymagnesium bromide (2b) and primary amines (e.g. aniline, aminopyridines) far more reactive than secondary amines (e.g. 2‐(methylamino)pyridine). The scope of the reaction was widened considerably by the application of microwaves, which allowed reactions to be carried out at much higher temperature than the boiling point of the solvent (i.e. tetrahydrofuran, b.p. 67°C). Copyright © 2003 John Wiley & Sons, Ltd.
Precision of the CASL‐perfusion MRI technique for the measurement of cerebral blood flow in whole brain and vascular territories
Authors: Floyd Thomas F. , Ratcliffe Sarah J. , Wang Jiongjiong , Resch Brooke , Detre John A.
Published: November 2003

Purpose

To analyze the precision of cerebral blood flow (CBF) measurements made with continuous arterial spin labeling(CASL) perfusion magnetic resonance imaging (MRI) over experimentally relevant intervals.

Materials and Methods

CASL perfusion MRI measurements of CBF on a 1.5‐T GE Signa magnet were repeated in young healthy male and female subjects at one hour and one week. Precision of the measurement was evaluated at both time intervals.

Results

CASL perfusion MRI measurements of CBF yielded within‐subject coefficients of variation (wsCV) of 5.8% for global and 13% for individual vascular regions when measurements were repeated within one hour. Differences in these values represent the error in post‐processing. Global and regional CBF measurements over one week yielded wsCVs of 13% and 14%, respectively. At one week, error secondary to physiologic variability affected global and regional measurements to the same degree and masked the software post‐processing error seen at one hour. The magnitude of the difference in repeated measures correlated with the magnitude of the measurement.

Conclusion

CASL perfusion MRI CBF measurements are accurate and precise. Variability over longer periods of time appears attributable to physiologic factors. Repeatability of the CASL measurement is sensitive to the magnitude of the measurement. This should be taken into account when studies requiring repeated measures involve subjects with significant variability in CBF. J. Magn. Reson. Imaging 2003;18:649–655. © 2003 Wiley‐Liss, Inc.
MRI for the diagnosis of pulmonary embolism
Authors: van Beek Edwin J.R. , Wild Jim M. , Fink Christian , Moody Alan R. , Kauczor Hans‐Ulrich , Oudkerk Matthijs
Published: November 2003

Pulmonary embolism (PE) is one of the most frequently encountered clinical emergencies. The diagnosis often involves multiple diagnostic tests, which need to be carried out rapidly to assist in the safe management of the patient. Recent strides in computed tomography (CT) have made big improvements in patient management and efficiency of diagnostic imaging. This review article describes the developments in magnetic resonance (MR) techniques for the diagnosis of acute PE. Techniques include MR angiography (MRA) and thrombus imaging for direct clot visualization, perfusion MR, and combined perfusion‐ventilation MR. As will be demonstrated, some of these techniques are now entering the clinical arena, and it is anticipated that MR imaging (MRI) will have an increasing role in the initial diagnosis and follow‐up of patients with acute PE. J. Magn. Reson. Imaging 2003;18:627–640. © 2003 Wiley‐Liss, Inc.
A New Chemo‐Enzymatic Route to Side‐Chain Liquid‐Crystalline Polymers: The Synthesis and Polymerization of 6‐(4‐Methoxybiphenyl‐4′‐oxy)hexyl Vinyl Hexanedioate
Authors: Hao Xiaojuan , Albertin Luca , Foster L. John R. , Davis Thomas P. , Barner‐Kowollik Christopher
Published: November 2003

A novel synthetic method combining chemo and enzymatic synthesis strategies was employed to prepare a vinyl acetate type monomer, 6‐(4‐methoxybiphenyl‐4′‐oxy)hexyl vinyl hexanedioate (VA‐LC). Homo‐ and copolymers of VA‐LC with maleic anhydride (MAn) were prepared by conventional free radical polymerization using 2,2′‐azobisisobutyronitrile (AIBN) and 1,1′‐azobis (cyclohexane carbonitrile) (AHCN) as an initiator at 95 and 60 °C, respectively. The thermal properties of the generated polymeric material were investigated by differential scanning calorimetry (DSC), and the optical texture was inspected by polarizing optical microscopy (POM). While the monomer VA‐LC does not exhibit liquid‐crystalline properties, poly(VA‐LC), and the alternating copolymer of VA‐LC with maleic anhydride both displayed such properties.

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Mellin transforms of p‐adic Whittaker functions
Authors: Deitmar Anton
Published: November 2003

It is shown that Mellin transforms of p‐adic Whittaker functions exist for generic characters. For good choices of vectors they are rational functions. For class one vectors they can be calculated explicitly. It turns out that they are automorphic L‐factors times normalization factors. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Families of toric varieties
Authors: Halic Mihai
Published: November 2003

The goal of this article is to construct families of complete toric varieties over arbitrary bases, and to compute the cohomology of the total space. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Strength of the Macromonomer Strategy for Complex Macromolecular Architecture: Molecular Characterization, Properties and Applications of Polymacromonomers
Authors: Hadjichristidis Nikos , Pitsikalis Marinos , Iatrou Hermis , Pispas Stergios
Published: November 2003

The efficiency of the macromonomer (MM) synthetic strategy for the creation of nonlinear complex macromolecular architectures (miktoarm stars, α,ω‐branched polymers, random/exact comb and graft copolymers, dendritic polymers, molecular brushes) is reviewed. In addition, the solution/bulk properties and the potential applications of polymacromonomers (PMM), as well as new synthetic ideas are presented. The synthesis of macromonomers and living polymacromonomers in situ leads to many novel linear and nonlinear structures, as for example PMM‐b‐PS‐b‐PMM, (PS)2PMM. The use of multichlorosilylstyrenes as monomer/linking agents opens new ways for structures with multichain macromonomeric building blocks.

The use of multichlorosilylstyrenes as monomer/linking agents opens new ways for structures having multichain macromonomeric building blocks.

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The use of multichlorosilylstyrenes as monomer/linking agents opens new ways for structures having multichain macromonomeric building blocks.
Impaired heteronymous somatosensory motor cortical inhibition in dystonia
Authors: Bertolasi Laura , Romito Silvia , Tinazzi Michele , Rizzuto Niccoló , Priori Alberto
Published: November 2003

A typical pathophysiological abnormality in dystonia is cocontraction of antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal cord. Recent experimental data have shown that inhibitory interactions between antagonist muscles have also a parallel control at the level of the sensorimotor cortex. The aim of this work was to study heteronymous effects of a median nerve stimulus on the corticospinal projections to forearm muscles in dystonia. We used the technique of antagonist cortical inhibition, which assesses the conditioning effect of median nerve afferent input on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia participated in the study. MEPs and somatosensory evoked potentials were normal in patients. In healthy subjects, median nerve stimulation at 15‐ to 18‐msec intervals inhibited the test MEPs in forearm extensors. In dystonic patients, median nerve stimulation delivered at the same conditioning–test intervals elicited significantly less inhibition of the test MEP. On the whole, these data suggest an impaired sensory–motor integration in dystonia and, more specifically, the decreased antagonistic cortical inhibition could suggest that functional interactions between antagonist muscles are primarily impaired at the cortical level. © 2003 Movement Disorder Society
Subthalamic lesion and paroxysmal tonic spasms
Authors: Garcia‐Ruiz Pedro J. , Villanueva Vicente , Gutierrez‐Delicado Eva , Echeverría Amaia , Perez‐Higueras Antonio , Serratosa José M.
Published: November 2003

Paroxysmal dyskinesia due to a subthalamic lesion is a rare finding. We describe a patient with paroxysmal tonic spasms due to a well‐defined lesion in the subthalamic area. In this case, we confirm the nonepileptic nature of the episode and collect with detail the clinical features by means of a video‐electroencephalographic recording. We also report an excellent response to carbamazepine in subthalamic paroxysmal dyskinesias. © 2003 Movement Disorder Society
Periodic limb movement during sleep developed after pontine lesion
Authors: Kim Joong‐Seok , Lee Sang‐Bong , Park Soung‐Kyeong , Han Si‐Ryung , Kim Yeong‐In , Lee Kwang‐Soo
Published: November 2003

We describe 2 patients who suffered a pontine infarction and subsequently developed periodic leg movement (PLM). The temporal relationship between a stroke and subsequent PLM, as well as the absence of sleep‐related disorders in patients' histories, favors the argument of a cause‐and‐effect relationship, with the observed association providing evidence for an anatomic substrate for PLM. © 2003 Movement Disorder Society
Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease
Authors: Herzog Jan , Reiff Julia , Krack Paul , Witt Karsten , Schrader Bettina , Müller Dieter , Deuschl Günther
Published: November 2003

Deep brain stimulation of the subthalamic nucleus (STN–DBS) is an established therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms induced by STN–DBS occurred in a previously psychiatrically healthy patient, focusing on the role of STN–DBS in influencing not only motor but also emotional behaviour. © 2003 Movement Disorder Society
Adult onset Niemann‐Pick type C disease: A clinical, neuroimaging and molecular genetic study
Authors: Battisti Carla , Tarugi Patrizla , Dotti Maria Teresa , De Stefano Nicola , Vattimo Angelo , Chierichetti Francesea , Calandra Sebastiano , Federico Antonio
Published: November 2003

We report on a patient with adult‐onset Niemann‐Pick type C (NPC) disease, carrying the mutations P1007 and I1061T in the NPC1 gene, presenting with marked psychiatric changes followed by dystonia and cognitive impairment. Filipin staining, single photon emission computed tomography perfusional, positron emission tomography metabolic, conventional magnetic resonance imaging, and magnetic resonance spectroscopy findings suggested a pathophysiological correlation with phenotype expression. This case expands the clinical and genetic spectrum of the rare adult‐onset NPC disease phenotype. © 2003 Movement Disorder Society
Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L‐dopa and ropinirole in the MPTP‐lesioned marmoset
Authors: Hill Michael P. , Bezard Erwan , McGuire Steven G. , Crossman Alan R. , Brotchie Jonathan M. , Michel Ann , Grimée Renee , Klitgaard Henrik
Published: November 2003

Long‐term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP–lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L‐dopa) or (2) ropinirole/L‐dopa combination. Oral administration of levetiracetam (13–60 mg/kg) in combination with either L‐dopa (12 mg/kg) alone or L‐dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L‐dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action. © 2003 Movement Disorder Society
Mesencephalic cryptococcal abscesses presenting with parkinsonism as an initial manifestation of AIDS
Authors: Bouffard John‐Paul , Mena Hernando , Ripple Mary , Troncoso Juan
Published: November 2003

Parkinsonism has been associated with HIV/AIDS and cerebral cryptococcal disease, but to date there has been no report of histological cryptococcal lesions in the substantia nigra (SN) in a patient with parkinsonism. We report on a case of a 63‐year‐old man who presented with tremor, gait disturbance, and mask‐like facies, and showed cryptococcal meningoencephalitis with cryptococcal abscesses in the SN at autopsy, without Lewy bodies or significant degeneration of the SN neurons. Parkinsonism also represented the first manifestation of AIDS in this previously undiagnosed patient. This case highlights the importance of considering infectious etiologies in patients presenting with parkinsonism, and underscores the need for autopsy in evaluation of patients with new or unexplained movement disorders. Movement disorders in association with AIDS and mesencephalic mass lesions are discussed. © 2003 Movement Disorder Society
Effect of ethanol on the central oscillator in essential tremor
Authors: Zeuner Kirsten E. , Molloy Fiona M. , Shoge Richard O. , Goldstein Susanne R. , Wesley Robert , Hallett Mark
Published: November 2003

We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double‐blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three‐dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500‐g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator. © 2003 Movement Disorder Society
Olfaction in essential tremor patients with and without isolated rest tremor
Authors: Louis Elan D. , Jurewicz Eva C.
Published: November 2003

An olfactory deficit is present in patients with essential tremor (ET), but it is often milder than that in patients with Parkinson's disease (PD). In both, the deficit occurs early in the disease. Isolated rest tremor without other signs of parkinsonism can occur in patients with ET. If the rest tremor in these patients represents a manifestation of ET rather than early PD, we hypothesized that their University of Pennsylvania Smell Identification Test (UPSIT) scores would be similar to those of ET patients without rest tremor. The mean UPSIT score in 13 ET patients with isolated rest tremor did not differ from that of 58 ET patients without rest tremor (29.3 ± 4.3 vs. 29.4 ± 6.4; P = 0.69). Several ET patients with rest tremor had UPSIT scores that fell outside of the range that is seen in 95% of patients with PD. These data raise the possibility that some ET patients with isolated rest tremor may not have early PD and that the pathological process that is responsible for their ET is also involving the basal ganglia. © 2003 Movement Disorder Society
Rapidly progressive parkinsonism in a self‐reported user of Ecstasy and other drugs
Authors: O'Suilleabhain Padraig , Giller Cole
Published: November 2003

A 38‐year‐old man developed parkinsonism that progressed to Hoehn and Yahr stage 5 within 4 years of onset. Response to ropinirole deteriorated, levodopa was not tolerated, and subthalamic nucleus stimulation has provided only partial relief of symptoms. He reported heavy use of Ecstasy through most of his twenties and thirties. His neurological problems may be unrelated to his drug use, but it is also possible they represent an idiosyncratic reaction. © 2003 Movement Disorder Society
Application of the model‐free approach to low molecular weight systems with hindered internal rotation: cinnamoylmesitylene
Authors: Denkova Pavletta S. , Dimitrov Valentin S. , Bakalova Snezhana M. , Kaneti Jose , Danov Krassimir
Published: November 2003

We investigated the molecular dynamics of the molecule of cinnamoylmesitylene, a substituted chalcone. Known rotation barriers for the OC‐4—C‐3C‐2 bond of substituted chalcones are in the range of values accessible to modern NMR techniques. The internal rotation about the C‐3—C‐4 bond is found to be fast relative to the complete lineshape analysis (CLSA) time‐scale. To determine the activation parameters of overall and internal motions of the molecule, the Lipari–Szabo model‐free analysis of the relaxation times and heteronuclear NOE data was used instead. Simultaneous analysis of both heteronuclear spin–lattice relaxation times and NOE data for the two carbon atoms C‐2 and C‐7 in the OC‐4—C‐3C‐2 and mesitylene fragments at different temperatures was performed. The correlation times and activation energies of overall and internal motions and the generalized order parameter, which are measures of the molecular mobility, were thus determined. The standard enthalpies of activation, ΔH≠, calculated from the experimental data for C‐2 and C‐7, are 5.6 and 6.6 kcal mol−1, respectively. Theoretical estimates of the barriers to internal rotations by ab initio MO calculations were made to verify the experimental results. The agreement between the NMR and theoretical results was good. Copyright © 2003 John Wiley & Sons, Ltd.
Solid‐state NMR studies of 1,3‐imidazolidine‐2‐selenone and some related compounds
Authors: Wazeer Mohamed I. M. , Isab Anvarhusein A. , Perzanowski Herman P.
Published: November 2003

Solid‐state cross‐polarization magic angle spinning 13C, 77Se and 15N NMR spectra were recorded for 1,3‐imidazolidine‐2‐selenone, its N‐substituted derivatives and some related compounds. The spinning sideband manifold intensities were used to obtain principal values of 13C and 77Se chemical shift tensors. Large selenium chemical shift anisotropies were observed for these selenones. Copyright © 2003 John Wiley & Sons, Ltd.
Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies
Authors: Figarella‐Branger Dominique , Civatte Muriel , Bartoli Catherine , Pellissier Jean‐François
Published: November 2003

The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and sporadic inclusion‐body myositis (s‐IBM). In DM, the main immune effector response appears to be humoral and directed against the microvasculature, whereas in both PM and s‐IBM, cytotoxic CD8+ T cells and macrophages invade and eventually destroy nonnecrotic muscle fibers expressing major histocompatibility complex class I. The need for more specific and safer therapies in inflammatory myopathies has prompted researchers to better decipher the molecular events associated with inflammation and muscle fiber loss in these diseases. The complex specific migration of leukocyte subsets to target tissues requires a coordinated series of events, namely activation of leukocytes, adhesion to the vascular endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a major role in this multistep process. In addition, cytokines by stimulating CAM expression and orchestrating T‐cell differentiation also influence the immune response. This review focuses on recent advances in defining the molecular events involved in leukocyte trafficking in inflammatory myopathies. Specific topics include a concise summary of clinical features, pathological findings and immunopathology observed in inflammatory myopathies, background information about cytokines, chemokines and cell adhesion molecules, and the expression of these molecules in inflammatory myopathies. Muscle Nerve 28: 659–682, 2003
Isolated compression of the pectoral nerve resulting in atrophy of the major pectoral muscle
Authors: Gardetto Alexander , Thaler Claudia , Kiechl Stefan , Maurer Herbert , Piza‐Katzer Hildegunde
Published: November 2003

We report on two cases of isolated damage to a muscle branch of the lateral pectoral nerve. Diagnosis was established by the clinical presentation and electromyographic examination. In the few reported cases of such injuries, the cause was trauma to this region. However, in both of our patients, focal muscle atrophy gradually developed after initiation of training schedules to increase the cross‐section of the major pectoral muscle; we therefore assume that compression injury to the nerve by repetitive muscle contractions may be of pathogenic relevance. Anatomical studies of this region showed that the nerve branches of the lateral pectoral nerve, having to pierce through a connective tissue septum that is thicker here by a few millimeters, may be subjected to additional risk of compression. Early recognition and treatment are vital to prevent associated morbidity of these rare but serious injuries. Muscle Nerve 28: 760–763, 2003
Management standards and development practice in the South African aid chain
Authors: Bornstein Lisa
Published: November 2003

The article addresses how South African non‐governmental organisations (NGOs) approach the management of their development activities and the influences upon their approaches. Based on interviews, field visits and programme documents from 40 organisations working in South Africa, the article explores the extent to which NGO programme priorities and adopted management practices arise out of donor conditions, succeed in their stated aims and generate other unintended consequences. Four aspects of contemporary NGO management dynamics are explored: logical frameworks, participatory processes, impact enhancement and financial probity. While donor requirements in these four areas generally impose heavy costs on South African NGOs and poorly achieve their stated aims, the research documents cases, in which local managers were able to work effectively and learn within these constraints, found ways around the more intrusive requirements, or challenged donors to change their policies to permit more equitable donor‐recipient relationships and better development practice. However, an unintended impact of tighter funding requirements is an observable differentiation within the South African NGO sector, with smaller community‐based organisations excluded as larger professional organisations establish more enduring links with international development organisations. Copyright © 2003 John Wiley & Sons, Ltd.
Approach to the study of C‐glycosyl flavones by ion trap HPLC‐PAD‐ESI/MS/MS: application to seeds of quince (Cydonia oblonga)
Authors: Ferreres Federico , Silva Branca M. , Andrade Paula B. , Seabra Rosa M. , Ferreira Margarida A.
Published: November 2003

Ion trap HPLC‐PAD‐ESI/MS/MS has been used to study C‐glycosyl ﬂavones in quince seeds. Comparative analysis of the ions [(M‐H)‐60]−, [(M‐H)‐90]− and [(M‐H)‐120]− from 6‐C‐ and 8‐C‐glycosyl ﬂavone isomers, together with their respective retention times, allowed deductions to be made about the nature of the sugar units and the positions of C‐glycosylation. Vicenin‐2 (6,8‐di‐C‐glucosyl apigenin), lucenin‐2 (6,8‐di‐C‐glucosyl luteolin), stellarin‐2 (6,8‐di‐C‐glucosyl chrysoeriol), isoschaftoside (6‐C‐arabinosyl‐8‐C‐glucosyl apigenin), schaftoside (6‐C‐glucosyl‐8‐C‐arabinosyl apigenin), 6‐C‐pentosyl‐8‐C‐glucosyl chrysoeriol and 6‐C‐glucosyl‐8‐C‐pentosyl chrysoeriol were identiﬁed in quince seed. Copyright © 2003 John Wiley & Sons, Ltd.
Software validation for medical device manufacturing
Authors: Jones Randy D. , Stalling David L. , Davis Jon , Jurkovich Patrick , LaPointe Kirk
Published: November 2003

The recent guidance on 21 CFR 11, the upcoming deadline for European CE Marking, and the needs of quality system regulation (QSR) have generated much discussion about approaches to software validation. In this article, a view of software validation by the design team of a QSR medical device manufacturer of precision glycohemoglobin/hemoglobin variant high performance liquid chromatography (HPLC) instrument platforms is provided. The software includes manufacturing, accounting and customer modules in one application. The unique aspect of this manufacturer's approach was to start with a risk analysis and a quality assurance audit plan to check software modules. The article also shows how a quality assurance unit should be prepared to contribute regulatory expertise for software validations that incorporate GMP, ICH, GLP, ISO and accounting standards. Copyright © 2003 John Wiley & Sons, Ltd.