bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of free fatty acids on ACTH and cortisol secretion in anorexia nervosa
Authors: Lanfranco Fabio , Gianotti Laura , Picu Andreea , Giordano Roberta , Daga Giovanni Abbate , Mondelli Valeria , Malfi Giuseppe , Fassino Secondo , Ghigo Ezio , Arvat Emanuela
Published: April 2006

Objective: Free fatty acids (FFAs) exert a stimulatory effect on the hypothalamic–pituitary–adrenal (HPA) axis in animals and inhibit spontaneous ACTH and cortisol secretion in humans. Patients with anorexia nervosa display concomitant HPA axis hyperactivity and increased lipolysis. We studied the effects of a lipid load on ACTH and cortisol secretion in patients with anorexia nervosa in comparison with normal subjects.

Design: Eight women with anorexia nervosa (ANW; means ± s.e.m.: 23.9 ± 2.3 years of age; body mass index (BMI): 14.9 ± 0.6 kg/m2) and seven normal women (NW; 25.6 ± 2.3 years of age; BMI: 22.8 ± 1.9 kg/m2) had FFA, ACTH, cortisol, glucose and insulin levels measured in the morning every 30 min for 180 min during i.v. saline or lipid-heparin emulsion (LHE) infusion.

Results: During saline infusion, ACTH and cortisol levels decreased spontaneously in both groups, ACTH and cortisol levels in ANW being higher than in NW. LHE infusion led to increased FFA levels in both groups (P < 0.005). The ACTH and cortisol decrease in NW was more marked than during saline infusion (P < 0.05). LHE infusion in ANW was associated with a more pronounced decrease in ACTH levels than during saline infusion (P < 0.05), while cortisol levels were unchanged. At the end of the LHE infusion, a progressive decrease in FFA levels was associated with an increase in ACTH and cortisol concentrations in NW (P < 0.05) but not in ANW in whom FFA levels decreased to a lesser extent (P < 0.05).

Conclusions: This study showed that corticotroph sensitivity to the inhibitory effect of an FFA load is preserved in patients with anorexia nervosa, in spite of persistent adrenal hyperactivity.
The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option
Authors: El Fassi Daniel , Nielsen Claus H , Hasselbalch Hans C , Hegedüs Laszlo
Published: April 2006

We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves’ disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after reviewing the efficacy and safety in other autoimmune diseases, we propose that treatment with the B cell-depleting agent Rituximab may become a clinically relevant treatment option in selected cases of GD, particularly when complicated with thyroid-associated ophthalmopathy.
UV Radiation as a Potential Driving Force for Zooplankton Community Structure in Patagonian Lakes
Authors: Marinone María Cristina , Marque Silvina Menu , Suárez Diego Añón , Diéguez María del Carmen , Pérez Patricia , De Los Ríos Patricio , Soto Doris , Zagarese Horacio E.
Published: April 2006

This article explores the potential role of UV radiation (UVR) as an influence on zooplankton communities. In the first section we provide a general overview of UVR effects on freshwater zooplankton, with an emphasis on Argentine and Chilean environments. In the second section we present the results of a survey involving 53 temperate lakes across a gradient of UVR exposure to determine patterns of species richness and specific diversity. These community characteristics decreased at high potential UVR exposure (i.e. high mean water column irradiance or low lake optical density). A threshold value of mean water column irradiance of approximately 10% of the surface level seems to limit both richness and diversity to minimum values. On the basis of the collected evidence it is not possible to definitely conclude that UVR rather than another covarying factor is responsible for the decrease in specific diversity observed at the lowest end of lake optical depth. However, lakes with values above the previous threshold are likely to exhibit highly depauperate zooplankton communities regardless of the mechanism. As a cautionary note we suggest that changes in the optical characteristics (i.e. changes due to atmospheric conditions, precipitation patterns or vertical displacement of the tree line) may result in sudden shifts in zooplankton community structure.
Application of Time‐Resolved Polarization Fluorescence Spectroscopy in the Femtosecond Range to Photosynthetic Systems†
Authors: Akimoto Seiji , Mimuro Mamoru
Published: April 2006

Time‐resolved polarization fluorescence spectroscopy in the femtosecond range was applied to a photosynthetic antenna system. Specific signals of excited states were obtained by simultaneous measurements of fluorescence rise and decay curves and polarized spectroscopy. Relaxation processes of carotenoids, energy transfer from carotenoids to chlorophyll (Chl) a, and energy migration among pigment pools of Chl a and Chl b were clearly resolved. Two new characteristics of carotenoid molecules were revealed only by anisotropy measurements. A new singlet excited state between the well known S2 and S1 states was resolved by an intermediary anisotropy (r(t) = 0.30) for siphonaxanthin in chloroplasts of Codium fragile. Time‐dependent changes in anisotropy with an initial value of 0.52 (r(0) = 0.52) were recorded during the relaxation of lutein molecules in the light‐harvesting complexes II of Arabidopsis thaliana, and this was interpreted as a strong interaction between two lutein molecules in the pigment–protein complexes. Other examples of the application of this method were also discussed.
Assessment of the Spatial Distribution of Soil Properties in a Northern Everglades Marsh
Authors: Corstanje R. , Grunwald S. , Reddy K. R. , Osborne T. Z. , Newman S.
Published: April 2006

Florida Everglades restoration plans are aimed at maintaining and restoring characteristic landscape features such as soil, vegetation, and hydrologic patterns. This study presents the results from an exhaustive spatial sampling of key soil properties in Water Conservation Area 1 (WCA 1), which is part of the northern Everglades. Three soil strata were sampled: floc, upper 0‐ to 10‐cm soil layer, and 10‐ to 20‐cm soil layer. A variety of properties were measured including bulk density (BD), loss on ignition (LOI), total phosphorus (TP), total inorganic phosphorus (TIP), total nitrogen (TN), total carbon (TC), total iron (TFe), total magnesium (TMg), total aluminum (TAl), and total calcium (TCa). Interpolated maps and model prediction uncertainties of properties were generated using geostatistical methods. We found that the uncertainty associated with spatial predictions of floc, particularly floc BD, was highest, whereas spatial predictions of soil chemical properties such as soil Ca were more accurate. The resultant spatial patterns for these soil properties identified three predominant features in WCA 1: (i) a north to south gradient in soil properties associated with the predominant hydrological gradient, (ii) areas of considerable soil nutrient enrichment along the western canal of WCA 1, and (iii) areas of considerable Fe enrichment along the eastern canal. By using geostatistical techniques we were able to describe the spatial dynamics of soil variables and express these predictions with an acceptable level of uncertainty.
A Novel Extractant for Removal of Hazardous Metals from Preservative‐Treated Wood Waste
Authors: Kakitani Tomo , Hata Toshimitsu , Kajimoto Takeshi , Imamura Yuji
Published: April 2006

The purpose of this study was to develop a one‐step metal extraction process that would effectively remove hazardous elements from wood powder or chips of western hemlock [Tsuga heterophylla (Raf.) Sarg.] treated with chromated copper arsenate (CCA) preservative. In addition, we tested this method for wood treated with other copper‐based preservatives such as ammoniacal copper quaternary (ACQ) and copper, boron, and azole (CuAz). A bioxalate solution consisting of 0.125 M oxalic acid adjusted to pH 3.2 with sodium hydroxide was tested for its ability to extract chromium, copper, and arsenic from wood treated with CCA and copper from ACQ, CuAz, or a mixture of CCA‐, ACQ‐, and CuAz‐treated wood in single step. The extraction proceeded efficiently with 6 h of treatment, and was insensitive to the differences in chemical characteristics, including solubility of individual elements. After 6 h of treatment, approximately 90% of chromium, copper, and arsenic were effectively removed from wood treated with CCA or a mixture of CCA, ACQ, and CuAz and 90% of copper from ACQ‐ and CuAz‐treated wood. These results demonstrate that the solvent extraction technique using pH‐adjusted bioxalate solution with sodium hydroxide is a promising method for pollution minimization by various types of wastes contaminated with heavy metals and arsenic.
Kinetics of Base‐Catalyzed Dehydrochlorination of Hexachlorocyclohexanes: I. Homogeneous Systems
Authors: Ren Mingzhong , Peng Ping'an , Huang Weilin , Liu Xiangmei
Published: April 2006

Base‐catalyzed dehydrochlorination of α‐, β‐, and γ‐hexachlorocyclohexane (HCH) was examined at different pH and temperature conditions. No reaction was observed for β‐HCH under all tested conditions likely due to the fact that all chlorines are at the equatorial positions. Highly pH‐ and temperature‐dependent reaction rates were observed for α‐ and γ‐HCH, and pentachlorocyclohexenes (PCCHs) and 1,2,4‐ and 1,2,3‐trichlorobenzene (TCB) were detected as the intermediates and final products of the transformation of both α‐ and γ‐HCH. The pseudo‐first‐order rate constants of each step of the reactions were calculated at different T and pH conditions. For the first step, the rate constants were at approximately 0.0005 d−1 in solutions below pH 7.0, and increased by about an order of magnitude per pH unit from pH 7.01 to pH 12.02. The second‐order reaction rate constants (kb) of this step were 3.57 ± 0.03 and 3.19 ± 0.19 M−1 d−1, respectively, and the associated activation energies (Ea) at pH 9.26 were 60.4 ± 7.8 and 67.7 ± 8.7 kJ mol−1, respectively, for α‐ and γ‐HCH. The rate constants for the formation of 1,2,3‐TCB (k21) and 1,2,4‐TCB (k22) were 0.0032 ± 0.0001 d−1 and 0.051 ± 0.003 d−1 from α‐HCH, and 0.0017 ± 0.0001 d−1 and 0.0041 ± 0.0002 d−1 from γ‐HCH at pH 8.28 and 25°C. Both k21 and k22 also showed an increase by about one order of magnitude per pH unit from pH 8.28 to pH 12.02. The Ea values were 64.4 ± 6.8 and 88.8 ± 5.2 kJ mol−1, respectively, for the formation of 1,2,4‐TCB and 1,2,3‐TCB from α‐HCH, and 70.6 ± 8.7 and 92.0 ± 4.9 kJ mol−1, respectively, for the formation of 1,2,4‐ and 1,2,3‐TCB from γ‐HCH at pH 9.26. Data provided by this study may be used for calculation of the percentages of the TCBs formed at different environmental conditions.
Expressive ways of knowing and transformative learning
Authors: Davis‐Manigaulte Jacqueline , Yorks Lyle , Kasl Elizabeth
Published: April 2006

This chapter offers a conceptual map for describing different means by which expressive ways of knowing support a holistic approach to transformative learning
Multivalent‐Ion‐Mediated Stabilization of Hydrogen‐Bonded Multilayers
Authors: Quinn J. F. , Caruso F.
Published: April 2006

Hydrogen‐bonding interactions are an important alternative to electrostatic interactions for assembling multilayer thin films of uncharged components. Herein, a new method is reported for rendering such films stable at pH values close to physiological conditions. Multilayer films based on hydrogen bonding are assembled by the alternate deposition of poly[(styrene sulfonic acid)‐co‐(maleic acid)] (PSSMA) and poly(N‐isopropylacrylamide) (PNiPAAm) at pH 2.5. The use of PSSMA results in multilayers that contain free styrene sulfonate groups, as these moieties do not interact with the PNiPAAm functional groups. Subsequent infiltration of a multivalent ion (Ce4+ or Fe3+) leads to an increase in the total film mass, with little impact on the film morphology, as determined by using atomic force microscopy. To examine the film stability, the resulting films have been exposed to elevated pH (7.1). While there is substantial swelling of the multilayers (25 % and 55 % for Ce4+‐ and Fe3+‐stabilized films, respectively), film loss is negligible. This provides a stark contrast with non‐stabilized films, which disassemble almost immediately upon exposure to pH 7.1. This method represents a simple and effective strategy for stabilizing hydrogen‐bonded structures non‐covalently. Further, the multivalent ions also render the films responsive to changes in the local redox environment, as demonstrated by film disassembly after exposure of Fe3+‐treated films to iodide solutions.
Pervasive developmental disorders in Prader–Willi syndrome: The Leuven experience in 59 subjects and controls
Authors: Descheemaeker Mie‐Jef , Govers Veerle , Vermeulen Peter , Fryns Jean‐Pierre
Published: April 2006

In the present study we investigated the co‐morbidity of pervasive developmental disorder (PDD) in 59 Prader–Willi syndrome (PWS) individuals and in 59 non‐specific mentally retarded controls, matched for IQ, gender, and age. The ‘Pervasive Developmental Disorder Mentally Retardation Scale’ (PDD‐MRScale), a screening questionnaire based on the DSM‐III‐R criteria for PDD, has been applied in the PWS group and in the control group. Results of the present study revealed a striking autistic‐like behavioral phenotype in the majority of the PWS individuals, particularly deficits in the quality of language and communication and of imagination and interests. This intersection with autistic symptomatology is an important addition to the behavioral phenotype in PWS persons. A first approach to delineate subtypes of autistic symptomalogy among PWS persons was performed. Nineteen percent of the PWS group did meet the full diagnostic DSM‐III‐R criteria for PDD in comparison with 15% in the control group. Results revealed that a higher IQ in PWS does not protect to develop genuine PDD and that uniparental disomy/imprinting mutation as genetic origin seems to be an additional risk factor for developing genuine PDD. The results of the present study suggest the importance of reconsidering the commonly recognized obsessive‐compulsive like behavior in PWS persons within the broader spectrum of autism disorders. © 2006 Wiley‐Liss, Inc.
Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence
Authors: Zhang Huiping , Ozbay Fatih , Lappalainen Jaakko , Kranzler Henry R. , van Dyck Christopher H. , Charney Dennis S. , Price Lawrence H. , Southwick Steven , Yang Bao‐Zhu , Rasmussen Ann , Gelernter Joel
Published: April 2006

Genetic variation at the locus encoding the brain derived neurotrophic factor (BDNF) has been implicated in some neuropsychiatric disorders such as Alzheimer's disease (AD), affective disorders (AFDs), schizophrenia, and substance dependence. We therefore performed a mutation scan of the BDNF gene to identify novel gene variants and examined the association between BDNF variants and several neuropsychiatric phenotypes in European American (EA) subjects and controls. Using denaturing high performance liquid chromatography (dHPLC), we identified a novel variant (G−712A) in the putative promoter region. This variant and two previously reported BDNF SNPs (C270T and Val66Met) were genotyped in 295 patients with AD, 108 with AFDs, 96 with posttraumatic stress disorder (PTSD), 84 with schizophrenia, 327 with alcohol and/or drug dependence, and 250 normal control subjects. No association was found between these three BDNF gene variants and AD, AFDs, PTSD, or schizophrenia. However, there was a nominally higher frequency of the G−712A G‐allele and the G/G genotype in subjects with substance dependence than in controls (Allele: χ2 = 4.080, df = 1, P = 0.043; Genotype: χ2 = 7.225, df = 2, P = 0.027). Although after correction for multiple testing, the findings are not considered significant (threshold P‐value was set at 0.020 by the program SNPSpD), logistic regression analyses confirmed the modest association between SNP G−712A and substance dependence, when the sex and age of subjects were taken into consideration. The negative results for AFDs, PTSD, and schizophrenia could be due to the low statistical power. Further study with larger samples is warranted. © 2006 Wiley‐Liss, Inc.
Increase in bone marrow lesions associated with cartilage loss: A longitudinal magnetic resonance imaging study of knee osteoarthritis
Authors: Hunter David J. , Zhang Yuqing , Niu Jingbo , Goggins Joyce , Amin Shreyasee , LaValley Michael P. , Guermazi Ali , Genant Harry , Gale Daniel , Felson David T.
Published: April 2006

Objective

Although bone marrow lesions (BMLs) are powerful predictors of joint space loss as visualized on radiographs, the natural history of these lesions, their relationship to cartilage loss, and the association between change in these lesions and cartilage loss are unknown. These questions were tested using longitudinal magnetic resonance imaging (MRI) data in a natural history study of symptomatic knee osteoarthritis (OA).

Methods

MRI of the knee was performed at baseline, 15 months, and 30 months in 217 patients with primary knee OA (122 men, 95 women; mean ± SD age 66.4 ± 9.4 years). To assess mechanical alignment, long‐limb films were obtained at 15 months. Subchondral bone marrow abnormalities, graded in the medial and lateral tibiofemoral joints, were defined as poorly marginated areas of increased signal intensity in the marrow on fat‐suppressed, T2‐weighted images. Cartilage morphologic features in the medial and lateral tibiofemoral joints were scored at all time points using a semiquantitative scale. For each of the medial and lateral compartments, generalized estimating equations were used to evaluate the longitudinal relationship of tibiofemoral BMLs to the tibiofemoral cartilage score, with adjustment for malalignment.

Results

Fifty‐seven percent of knees had BMLs at baseline, of which 99% remained the same or increased in size at followup. Knee compartments with a higher baseline BML score had greater cartilage loss. An increase in BMLs was strongly associated with further worsening of the cartilage score. Enlarging or new BMLs occurred mostly in malaligned limbs, on the side of the malalignment (e.g., new medial BMLs in varus‐aligned knees). The association of BML change with medial tibiofemoral cartilage loss was not significant after adjusting for alignment.

Conclusion

Lesions of the bone marrow are unlikely to resolve and often get larger over time. Compared with BMLs that stay the same, enlarging BMLs are strongly associated with more cartilage loss. Furthermore, any change in BML is mediated by limb alignment.
Connective tissue growth factor/CCN2 overexpression in mouse synovial lining results in transient fibrosis and cartilage damage
Authors: Davidson E. N. Blaney , Vitters E. L. , Mooren F. M. , Oliver N. , Berg W. B. van den , Kraan P. M. van der
Published: April 2006

Objective

Characteristics of osteoarthritis (OA) include cartilage damage, fibrosis, and osteophyte formation. Connective tissue growth factor (CTGF; also known as CCN2), is found in high levels in OA chondrocytes and is frequently involved in fibrosis, bone formation, and cartilage repair. The present study was therefore undertaken to investigate the potential role of CTGF in OA pathophysiology.

Methods

We transfected the synovial lining of mouse knee joints with a recombinant adenovirus expressing human CTGF and measured synovial fibrosis and proteoglycan content in cartilage on days 1, 3, 7, 14, and 28. Messenger RNA (mRNA) expression in synovium and cartilage was measured on days 3, 7, and 21.

Results

CTGF induced synovial fibrosis, as indicated by accumulation of extracellular matrix and an increase in procollagen type I–positive cells. The fibrosis reached a maximum on day 7 and had reversed by day 28. Levels of mRNA for matrix metalloproteinase 3 (MMP‐3), MMP‐13, ADAMTS‐4, ADAMTS‐5, tissue inhibitor of metalloproteinases 1 (TIMP‐1), and transforming growth factor β were elevated in the fibrotic tissue. TIMP‐1 expression was elevated on day 3, while expression of other genes did not increase until day 7 or later. CTGF induced proteoglycan depletion in cartilage as early as day 1. Maximal depletion was observed on days 3–7. Cartilage damage was reduced by day 28. A high level of MMP‐3 mRNA expression was found in cartilage. CTGF overexpression did not induce osteophyte formation.

Conclusion

CTGF induces transient fibrosis that is reversible within 28 days. Overexpression of CTGF in knee joints results in reversible cartilage damage, induced either by the high CTGF levels or via factors produced by the CTGF‐induced fibrotic tissue.
Mouse monoclonal anti–human thrombomodulin antibodies bind to and activate endothelial cells through NF‐κB activation in vitro
Authors: Nara Hiroyuki , Okamoto Hiroshi , Minota Seiji , Yoshio Taku
Published: April 2006

Objective

To clarify whether mouse monoclonal antibodies (mAb) against human thrombomodulin (TM), which react with human TM present on the endothelial cell (EC) surface, have anti–endothelial cell antibody (AECA) activity and influence antiinflammatory properties of human TM expressed on the EC surface in vitro.

Methods

Three preparations of mouse mAb against human TM that react with different sites of the human TM epidermal growth factor–like domain were tested for their ability to 1) bind to ECs, 2) modulate cytokine secretion from ECs, EC adhesion molecule expression, and neutrophil adhesion to ECs, and 3) stimulate nuclear translocation of NF‐κB through the degradation of cytoplasmic IκB in ECs. Recombinant human interleukin‐1β (IL‐1β) was used as a positive control, and mouse IgG1 and mouse IgG2a were used as negative controls.

Results

The 3 preparations of mouse mAb against human TM that bind to unfixed EC monolayers enhanced IL‐6 and IL‐8 secretion from ECs, up‐regulated expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 on EC monolayers, and enhanced neutrophil adhesion to ECs to a degree similar to that observed with IL‐1β stimulation, but they did not induce the secretion of tumor necrosis factor α or IL‐1β from ECs throughout the incubation period. The 3 preparations stimulated nuclear translocation of NF‐κB through the degradation of cytoplasmic IκB. Mouse IgG1 and mouse IgG2a did not exhibit such effects.

Conclusion

These results suggest the possibility that AECA can react with antigens such as TM that are present on the EC surface and activate ECs. Such events on ECs may lead to vascular inflammation and damage in patients with connective tissue diseases and vasculitis in which AECA are present.
Lupus‐like disease and high interferon levels corresponding to trisomy of the type I interferon cluster on chromosome 9p
Authors: Zhuang Haoyang , Kosboth Mona , Lee Pui , Rice Amanda , Driscoll Daniel J. , Zori Roberto , Narain Sonali , Lyons Robert , Satoh Minoru , Sobel Eric , Reeves Westley H.
Published: April 2006

Objective

Systemic lupus erythematosus (SLE) is associated with type I interferons (IFNs) and can be induced by IFNα treatment. This study looked for evidence of autoimmunity in a pedigree consisting of 4 family members with a balanced translocation 9;21 and 2 members with an unbalanced translocation resulting in trisomy of the short (p) arm and part of the long (q) arm of chromosome 9. These latter 2 subjects had 3 copies of the IFN gene cluster.

Methods

Subjects were evaluated clinically and serologically for autoimmune disease. Expression levels of IFNα4, IFNβ, the type I IFN–inducible gene Mx1, the type I IFN receptor, interleukin‐6, and tumor necrosis factor α were determined by real‐time polymerase chain reaction. Circulating plasmacytoid dendritic cells, the main IFN‐producing cells, were quantified by flow cytometry.

Results

Both subjects with trisomy of chromosome 9p had a lupus‐like syndrome with joint manifestations and antinuclear antibodies: one had anti‐RNP and antiphospholipid autoantibodies, and the other had anti–Ro 60. The 3 family members with a balanced translocation 9;21 had no clinical or serologic evidence of autoimmunity, similar to that in relatives who were unaffected by the chromosomal translocation. In the 2 subjects with trisomy of 9p, high levels of IFNα/β (comparable with those found in patients with SLE), increased signaling through the IFN receptor (as indicated by high Mx1 expression), and low levels of circulating plasmacytoid dendritic cells (as observed in patients with SLE) were evident. These abnormalities were not seen in individuals with a balanced translocation.

Conclusion

Trisomy of the type I IFN cluster of chromosome 9p was associated with lupus‐like autoimmunity and increased IFNα/β and IFN receptor signaling. The data support the idea that abnormal regulation of type I IFN production is involved in the pathogenesis of SLE.
Guillain‐Barré and Miller Fisher syndromes occurring with tumor necrosis factor α antagonist therapy
Authors: Shin In‐Sook J. , Baer Alan N. , Kwon Hyon J. , Papadopoulos Elektra J. , Siegel Jeffrey N.
Published: April 2006

Objective

Diverse neurologic syndromes have been described in association with tumor necrosis factor α (TNFα) antagonist therapy for inflammatory arthritides and Crohn's disease. The objective of this study was to review the occurrence and clinical features of Guillain‐Barré syndrome and its variant, the Miller Fisher syndrome, during TNFα antagonist therapy.

Methods

The postmarketing database of the US Food and Drug Administration (FDA) was searched, following our experience with a patient with rheumatoid arthritis in whom the Miller Fisher syndrome variant of the Guillain‐Barré syndrome developed while he was receiving infliximab therapy.

Results

Our index patient had a neurologic illness defined initially by ataxia and dysarthria, which fluctuated in relation to each subsequent infliximab infusion and, after 6 months, culminated in areflexic flaccid quadriplegia. In addition, 15 patients in whom Guillain‐Barré syndrome developed following TNFα antagonist therapy were identified from the FDA database. Guillain‐Barré syndrome developed following infliximab therapy in 9 patients, following etanercept therapy in 5 patients, and following adalimumab therapy in 1 patient. Among the 13 patients for whom followup data were available, 1 patient experienced no resolution, 9 patients had partial resolution, and 3 patients had complete resolution of Guillain‐Barré syndrome following therapy.

Conclusion

An association of Guillain‐Barré syndrome with TNFα antagonist therapy is supported by the worsening of neurologic symptoms that occurred in our index patient following each infusion of infliximab, and by the temporal association of this syndrome with TNFα antagonist therapy in 15 other patients. An acute or subacute demyelinating polyneuropathy should be considered a potential adverse effect of TNFα antagonist therapy.
Brachio‐cervical inflammatory myopathies: Clinical, immune, and myopathologic features
Authors: Pestronk Alan , Kos Ksenija , Lopate Glenn , Al‐Lozi Muhammad T.
Published: April 2006

Objective

To characterize patients with inflammatory myopathies who present with weakness in the proximal regions of the arms.

Methods

Clinical, laboratory, and myopathologic features were evaluated in 10 patients, identified consecutively over 12 years, with inflammatory myopathies and weakness that was most severe in the proximal regions of the arms. The features of these brachio‐cervical inflammatory myopathy (BCIM) syndromes were compared with those of other inflammatory and immune‐mediated myopathies evaluated during the same period.

Results

Patients with BCIM developed progressive weakness at ages 24–82 years (mean ± SD age 55 ± 9 years). Posterior neck weakness occurred in 60% of patients, while motor neuron disease was the referring diagnosis in 30%. All patients had other systemic autoimmune disorders, including myasthenia gravis (40%) and rheumatoid arthritis (20%). Antinuclear antibodies were present in all patients. Serum creatine kinase levels were usually moderately high (mean 910 IU/liter). Active myopathy was identified in muscle biopsy samples from the patients. Focal collections of mononuclear cells, some predominantly B cells, were present in perivascular and perimysial regions. MxA‐ and CD123‐positive dendritic cells were present in the endomysium. C5b–9 components of complement were present diffusely in endomysial connective tissue. Most patients improved in strength after receiving corticosteroids.

Conclusion

Patients with BCIM syndromes have progressive weakness in the proximal regions of the arms and neck. The predominant myopathologic findings are active myopathy, C5b–9 staining of endomysium, focal perivascular and perimysial inflammation, often with a prominent B cell component, and endomysial dendritic cells. Corticosteroid treatment of BCIM is often followed by improvement in strength.
Alefacept in combination with methotrexate for the treatment of psoriatic arthritis: Results of a randomized, double‐blind, placebo‐controlled study
Authors: Mease Philip J. , Gladman Dafna D. , Keystone Edward C.
Published: April 2006

Objective

To evaluate the efficacy and safety of alefacept in combination with methotrexate (MTX) for the treatment of psoriatic arthritis (PsA).

Methods

Patients were eligible for this randomized, double‐blind, placebo‐controlled trial if they were ages 18–70 years and had active PsA (≥3 swollen joints and ≥3 tender joints) despite treatment with MTX for ≥3 months (a stable dosage for ≥4 weeks prior to enrollment). Patients were stratified according to psoriasis body surface area (BSA) involvement (≥3% or <3%). Alefacept (15 mg) or placebo was administered intramuscularly once weekly for 12 weeks in combination with MTX, followed by 12 weeks of observation during which only MTX treatment was continued. The primary efficacy end point was the proportion of patients achieving a 20% improvement in disease activity according to the American College of Rheumatology criteria (an ACR20 response) at week 24.

Results

One hundred eighty‐five patients were randomly assigned to receive alefacept plus MTX (n = 123) or placebo plus MTX (n = 62). At week 24, 54% of patients in the alefacept plus MTX group achieved an ACR20 response, compared with 23% of patients in the placebo plus MTX group (P < 0.001). Mean reductions in tender and swollen joint counts in patients receiving alefacept plus MTX were –8.0 and –6.3, respectively. In patients with psoriasis involving ≥3% BSA (n = 87), a 50% reduction from the baseline Psoriasis Area Severity Index at week 14 was achieved by 53% of patients receiving alefacept plus MTX compared with 17% of those receiving placebo plus MTX (P < 0.001). Most adverse events were mild to moderate in severity. In the alefacept plus MTX group, the incidence of serious adverse events was low (1.6%), and no opportunistic infections or malignancies were reported.

Conclusion

Alefacept in combination with MTX may be an effective and safe treatment for PsA.
The sensitive determination of nucleic acids using a fluorescence‐quenching method
Authors: Jia Zhen , Yang Jinghe , Wu Xia , Sun Changxia , Wang Fei , Liu Shufang , Wang Feng
Published: April 2006

Experiments indicated that nucleic acids can quench the fluorescence of the Eu3+–2‐thenoyltrifluoroacetone (TTA)–1,10‐phenanthroline (Phen) system. Based on this, a sensitive method for the determination of nucleic acids was proposed. The experiments indicated that under the optimum conditions, the quenched fluorescence intensity was in proportion to the concentration of nucleic acids in the range 1.0 × 10−11–1.0 × 10−6 g/mL for yeast RNA (yRNA), 5.0 × 10−11–5.0 × 10−7 g/mL for fish sperm (fsDNA) and 1.0 × 10−10–1.5 × 10−6 g/mL for calf thymus DNA (ctDNA). Their detection limits were 3.0 × 10−12, 4.0 × 10−12 and 5.0 × 10−11 g/mL, respectively. Therefore, the proposed method is one of the most sensitive methods available. The interaction between nucleic acids and Eu3+‐TTA‐Phen is also discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Alteration of monocytic cell oxidative burst caused by methacrylic monomers present in dental materials: a chemiluminescence study
Authors: Nocca Giuseppina , Sole Pasquale De , Gambarini Gianluca , Palma Francesco De , Parziale Vito , Giardina Bruno , Lupi Alessandro
Published: April 2006

Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are photo‐polymerized, but this reaction is never complete, so release of uncured monomers in the periapical tissues and in biological fluids may happen and, potentially, alter the repair of pulpal and of periapical lesions by interfering with local phagocytes. The aim of this study was the evaluation of the functional activity of the monocyte–macrophage system after incubation with methacrylic monomers. The oxidative burst of two cellular systems was analysed using the chemiluminescence technique. Data were collected and statistically analysed. Monomers were found to reduce the in vitro oxidative burst of phagocytes independently from their cytotoxicity. These findings demand further evaluation of the effects of oxidative burst alteration in monocyte–macrophage function and may prompt the inclusion of the described chemiluminescence test in biocompatibility preliminary studies of dental materials. Copyright © 2006 John Wiley & Sons, Ltd.
Determination of iodide using flow injection with acidic potassium permanganate chemiluminescence detection
Authors: Yaqoob Mohammad , Atiq‐ur‐Rehman  , Waseem Amir , Nabi Abdul
Published: April 2006

A simple and rapid flow‐injection method is described for the determination of iodide, based on potassium permanganate chemiluminescence detection via oxidation of formaldehyde in aqueous hydrochloric acid. The calibration graph was linear over the range 1.0–12 × 10−6 mol/L (r2 = 0.9955) with relative standard deviations (n = 4) in the range 1.0–3.5%. The detection limit (3σ) was 1.0 × 10−7 mol/L, with sample throughput of 120/h. The effect of interfering cations [Ca(II), Mg(II), Ni(II), Fe(II), Fe(III) and Pb(II)] and anions (Cl−, SO42−, PO43−, NO3−, NO2−, F− and SO32−) were studied. The method was applied to iodized salt samples and the results obtained in the range 0.03 ± 0.005–0.10 ± 0.006 mg I/g were in reasonable agreement with the amount labelled. The method was statistically compared with the results obtained by titration; no significant disagreement at 95% confidence was observed. Copyright © 2006 John Wiley & Sons, Ltd.
Ruthenium Complexes of Thiocinnamaldehydes: Synthesis, Structure, and [4+2]‐Cycloaddition Reactions
Authors: Schenk Wolfdieter A. , Beucke Thomas , Burzlaff Nicolai , Klüglein Matthias , Stemmler Marco
Published: April 2006

Ruthenium hydrogensulfido complexes [CpRu(PP)(SH)] ((PP)Ph2PCH2PPh2 (dppm), Ph2PC2H4PPh2 (dppe)) were obtained from the corresponding chloro complexes by Cl/SH exchange. Condensation with a range of cinnamaldehydes gave thiocinnamaldehyde complexes [CpRu(PP)(SCHCR2CHR1)]PF6 (R1=C6H4X, R2=H, Me, X=H, OMe, NMe2, Cl, NO2) as highly‐colored crystalline compounds. The thiocinnamaldehyde complexes undergo [4+2]‐cycloaddition reactions with vinyl ethers CH2CHOR3 (R3=Et, Bu) and styrenes H2CCHC6H4Y (Y=H, Me, OMe, Cl, Br, NO2) to give complexes of 2,4,5‐trisubstituted 3,4‐dihydro‐2H‐thiopyrans as mixtures of two diastereoisomers. The rate of addition of para‐substituted styrenes H2CCHC6H4Y to [CpRu(dppm)(SCHCHCHPh)]PF6 increases in the series Y=NO2, Br, Cl, H, Me, OMe, indicating that the cycloaddition is dominated by the HOMO(dienophile)–LUMO(diene) interaction. The strained dienophiles norbornadiene and norbornene also add, giving ruthenium complexes of 3‐thia‐tricyclo[6.2.1.02,7]undeca‐4,9‐dienes and 3‐thia‐tricyclo[6.2.1.02,7]undec‐4‐enes, respectively. Addition reactions with acrolein, methacrolein, methyl vinyl ketone, acrylic ester, or ethyl propiolate finally yielded ruthenium complexes of 3,4‐disubstituted 3,4‐dihydro‐2H‐thiopyrans and 4H‐thiopyrans, respectively.
Macropodumines A–C: Novel Pentacyclic Alkaloids with an Unusual Skeleton or Zwitterion Moiety from Daphniphyllum macropodum Miq.
Authors: Zhang Wen , Guo Yue‐Wei , Krohn Karsten
Published: April 2006

Three novel alkaloids, macropodumines A–C (1–3), were isolated from the stem of Daphniphyllum macropodum Miq. Interestingly, the structure of macropodumine A (1) was characterized as having a fused pentacyclic system including an unusual eleven‐membered macrolactone ring, whereas macropodumine B (2) contains a rare cyclopentadienyl carbanion, which is stabilized as a zwitterion by an internal iminium cation. The structures of these new metabolites were established on the basis of their detailed spectroscopic analysis. In particular, the unique structure of zwitterion 2 was further confirmed by using single‐crystal X‐ray diffraction analysis.
Electron Transfer in Nonpolar Solvents in Fullerodendrimers with Peripheral Ferrocene Units
Authors: Pérez Laura , García‐Martínez Joaquín C. , Díez‐Barra Enrique , Atienzar Pedro , García Hermenegildo , Rodríguez‐López Julián , Langa Fernando
Published: April 2006

Two new fullerodendrimers, with two and four ferrocene units on their periphery, have been synthesized by 1,3‐dipolar cycloaddition reactions between the corresponding azomethine ylides and C60. These new compounds have been studied by using cyclic voltammetry and UV/Vis spectroscopy. Weak intramolecular interactions between the fullerene cage and the ferrocene groups have been found. The photochemical events of both fullerene–ferrocene dendrimers have been probed by means of steady‐state and time‐resolved techniques. The steady‐state emission intensities of the fulleropyrrolidine–ferrocene dendrimers 1 and 2 were found to be quenched relative to the N‐methylfulleropyrrolidine without substituents that was used as a model. The nanosecond transient absorption spectral studies revealed efficient charge separation in both systems, even in toluene. The lifetimes of the (C60).−–(dendron).+ are higher for the second‐generation fullerodendrimer (with four ferrocene units) and they are of the order of tens of nanoseconds in toluene and hundreds of nanoseconds in polar solvents.
Novel method for cell debris removal in the flow cytometric cell cycle analysis using carboxy‐fluorescein diacetate succinimidyl ester
Authors: Terho Perttu , Lassila Olli
Published: April 2006

Background:

Cell cycle analysis with flow cytometry using propidium iodide (PI) can be difficult in some cases because of the cell debris. Here, we introduce debris removal using intranuclear protein staining (DRIPS), a novel method for separating intact nuclei and cell debris to different populations using carboxy‐fluorescein diacetate succinimidyl ester (CFSE).

Methods:

To study the apoptosis‐sensitivity, chicken DT40 B cell lymphoma cell line was γ irradiated. After the irradiation, the cells were incubated up to 8 h and the stages of the cell cycle were followed with flow cytometry.

Results:

CFSE staining, done simultaneously with PI, stained the cell debris brighter than intact nuclei and could be excluded from the histogram with a simple gating procedure. The method is reliable and reproducible and can be executed within 15 min.

Conclusions:

DRIPS‐method greatly enhances the analysis of difficult cell cycle samples. © 2006 International Society for Analytical Cytology
Synthesis and Structure of Trialkyltantalum Complexes Stabilized by Aminopyridinato Ligands
Authors: Noor Awal , Kretschmer Winfried , Kempe Rhett
Published: April 2006

(4‐Methylpyridin‐2‐yl)(trimethylsilyl)amine (1), (6‐methylpyridin‐2‐yl)(trimethylsilyl)amine (2), and (2,6‐diisopropylphenyl)(pyridin‐2‐yl)amine (3) were deprotonated and used as ligands to synthesize trialkyltantalum complexes. The reaction of 2 equiv. of 1 or 2 with pentabenzyltantalum afforded tribenzyltantalum(V) complexes by toluene elimination. Analogous reaction using 3 failed. Lithiation of 3 followed by the reaction with tribenzyltantalum dichloride gave rise to the corresponding tribenzyl complex. Other alkyltantalum complexes stabilized by this ligand environment can be prepared by treating tantalum pentachloride with 2 equiv. oflithiated 3 to form a bis(aminopyridinato)tantalum trichloride. The reaction of this trichloride with 3 equiv. of alkyllithium compounds like methyllithium affords the corresponding trialkyltantalum complexes. X‐ray diffraction studies of four of the synthesized complexes were carried out. They adopt two different coordination environments, either slightly distorted capped octahedrons (sterically less demanding aminopyridinato ligands) or pentagonal bipyramids (bulkier aminopyridinato ligands). The alkyl species were surprisingly stable at elevated temperatures and no formation of mixed alkyl/alkylidene complexes was observed. Alkyl cation formation and the behaviour of a selection of these compounds in olefin polymerization were explored. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Intramolecular controls for the generation of clinical‐quality SNP genotypes and the assessment of normal heterozygote imbalance
Authors: McKeown Brian , Rowan Paul , Sung Robert , Derbyshire Roger
Published: April 2006

We present an inventive method that generates intramolecular controls for SNP analysis, termed Mirror SNPs. Using the ovine diseases of callipyge and scrapie as examples, we describe the PCR‐driven production of balanced heterozygote copies of the various SNPs implicated in these diseases. In the absence of a callipyge‐positive control DNA, we generated a balanced heterozygote Mirror SNP that represents both the wild‐type and mutant forms of the causal polymorphism. Simultaneous analysis of this artificial Mirror SNP and the Real (target) SNP was used to prove the absence of the mutant form of the nucleotide at the Real SNP position in tested samples. Scrapie susceptibility was assessed using a PCR‐driven system which generated four separate Mirror SNPs, and these enabled the confirmation of an apparent departure from ‘balanced’ heterozygote appearance at Real SNPs tested. Mirror SNP technology is generic and will enable the accurate assessment of rare and medically important SNP variants, more accurate frequency determinations, and the potential assessment of SNPs in ‘mixed template’ samples common in forensic analyses.
Capillary electrophoresis‐mass spectrometry of a new cross‐linker with acrylic functionality
Authors: Simó Carolina , Pérez Paloma , Neusüß Christian , Pelzing Matthias , San Román Julio , Gallardo Alberto , Cifuentes Alejandro
Published: April 2006

Analytical characterization of dimethacrylate‐tyrosine‐lysine‐tyrosine (DMTLT, a new biodegradable acrylic cross‐linker synthesized at our laboratory) is carried out using CE‐MS. DMTLT is a pseudopeptide composed by tyrosine‐lysine‐tyrosine amino acids linked through urea bonds with two methacrylic groups, one at each end of the molecule, making this compound an excellent cross‐linker for polymerization reactions and for obtaining new biodegradable materials. A new CE‐MS method is developed for the characterization of DMTLT and its products of degradation after basic hydrolysis. In order to carry out an exhaustive examination of such degradation products methods based on CE coupled to IT and TOF‐MS are employed. Based on CE‐IT‐MS results and the elemental composition of the degradation products obtained by CE‐TOF‐MS, conclusions on the mechanism and kinetic of hydrolysis of DMTLT are obtained confirming both the usefulness of CE‐MS to characterize new biomaterials and the applicability of DMTLT for preparing new biodegradable polymers. These results are corroborated through the CE‐MS detection of the identified products of degradation in a dimethyl acrylamide polymer cross‐linked with DMTLT.
Isolation, identification and characterisation of starch‐interacting proteins by 2‐D affinity electrophoresis
Authors: Kosar‐Hashemi Behjat , Irwin Jennifer A. , Higgins Jody , Rahman Sadequr , Morell Matthew K.
Published: April 2006

A 2‐D affinity electrophoretic technique (2‐DAE) has been used to isolate proteins that interact with various starch components from total barley endosperm extracts. In the first dimension, proteins are separated by native PAGE. The second‐dimensional gel contains polysaccharides such as amylopectin and glycogen. The migration of starch‐interacting proteins in this dimension is determined by their affinity towards a particular polysaccharide and these proteins are therefore spatially separated from the bulk of proteins in the crude extract. Four distinct proteins demonstrate significant affinity for amylopectin and have been identified as starch branching enzyme I (SBEI), starch branching enzyme IIa (SBEIIa), SBEIIb and starch phosphorylase using polyclonal antibodies and zymogram activity analysis. In the case of starch phosphorylase, a protein spot was excised from a 2‐DAE polyacrylamide gel and analysed using Q‐TOF MS/MS, resulting in the alignment of three internal peptide sequences with the known sequence of the wheat plastidic starch phosphorylase isoform. This assignment was confirmed by the determination of the enzyme's function using zymogram analysis. Dissociation constants (Kd) were calculated for the three enzymes at 4°C and values of 0.20, 0.21 and 1.3 g/L were determined for SBEI, SBEIIa and starch phosphorylase, respectively. Starch synthase I could also be resolved from the other proteins in the presence of glycogen and its identity was confirmed using a polyclonal antibody and by activity analysis. The 2‐DAE method described here is simple, though powerful, enabling protein separation from crude extracts on the basis of function.
A simple light‐emitted diode‐induced fluorescence detector using optical fibers and a charged coupled device for direct and indirect capillary electrophoresis methods
Authors: Arráez‐Román David , Fernández‐Sánchez Jorge F. , Cortacero‐Ramírez Sonia , Segura‐Carretero Antonio , Fernández‐Gutiérrez Alberto
Published: April 2006

We constructed a simple fluorescence detector for both direct and indirect CE methods using a blue light‐emitted diode (470 nm) as excitation source, a bifurcated optical fiber as a waveguide, and a CCD camera as a detector. The connection of all the components is fairly easy even for nonexperts and the use of a CCD camera improves the applicability of this detector compared to the others using PMTs because it permits the recording of 2‐D electropherograms or phosphorescence measurements. This detector provides a compact, low cost, and rapid system for the determination of native fluorescence compounds which have high quantum yields by CE with direct fluorescence detection, showing an LOD of 2.6×10−6 M for fluorescein; the determination of fluorescence derivative compounds by CE with direct fluorescence detection, showing an LOD of 1.6×10−7 M for FITC‐labeled 1,6‐diaminohexane; and nonfluorescence compounds by CE with indirect fluorescence detection with an LOD of 2.7×10−6 M for gallic acid.
Sheathless capillary electrophoresis‐mass spectrometry using a pulsed electrospray ionization source
Authors: Chao Bing‐Fong , Chen Chao‐Jung , Li Fu‐An , Her Guor‐Rong
Published: April 2006

A sheathless interface has been developed for coupling CE with electrospray IT mass spectrometer. This interface utilized a pulsed ESI source. The use of a pulsed electrospray source allows the use of a sprayer with larger orifice, and thus alleviates the problem of column clogging during conductive coating and CE analysis. A pulsed ESI source operated at 20 Hz and 20% duty cycle was found to produce the optimal signals. For better signals, the maximum ion injection time in the IT mass spectrometer has to be set to a value close to the actual spraying time (10 ms). Using a sprayer with 50 µm od, more stable and enhanced signals were obtained in comparison with continuous CE‐ESI‐MS under the same flow rate (150 nL/min). The utility of this design is demonstrated with the analysis of synthetic drugs by CE‐MS.