bluuebunny/crossref_metadata_2025 huggingface dataset:
Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: A cross validated retrospective assessment
Authors: Zein Claudia O. , Beatty Kristi , Post Anthony B. , Logan Laurie , Debanne Sara , McCullough Arthur J.
Published: November 2006

An epidemiological association between cigarette smoking and primary biliary cirrhosis (PBC) has been demonstrated. Our aim was to determine the relationship between smoking and severity of liver fibrosis at presentation in patients with PBC. All patients with PBC seen at the three major teaching hospitals of Case Western Reserve University between October 1998 and December 2005 were identified. Data obtained at the time of the first evaluation leading to the PBC diagnosis on 97 patients were collected. The cumulative number of cigarette packs smoked per year (pack-years) was calculated. Advanced histological disease was defined as Ludwig stages 3 or 4. Analyses were performed to determine associations between advanced histological disease, smoking and other variables related to liver fibrosis. Smoking history was more common (

P

= .0008) in patients with advanced histological disease at presentation compared to those with early disease. Among smokers, mean lifetime tobacco consumption was higher (

P

= .04) in cases with advanced histological disease at presentation (30 pack-years) compared to cases with early disease (17 pack-years). Logistic regression demonstrated a significant association between a lifetime tobacco consumption of ≥10 pack-years and advanced histological disease at presentation (OR = 13.3). The association remained significant after adjusting for age, gender, and alcohol intake. The validity of these results was corroborated by cross-validation in an independent confirmatory set of 172 patients with PBC.

In conclusion

, smoking may accelerate the progression of PBC. This could be induced by exposure to chemicals in cigarette smoke.
Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry
Authors: Andrade Raúl J. , Lucena Isabel M. , Kaplowitz Neil , García-Muņoz Beatriz , Borraz Yolanda , Pachkoria Ketevan , García-Cortés Miren , Fernández Carmen M. , Pelaez Gloria , Rodrigo Luis , Durán José A. , Costa Joan , Planas Ramón , Barriocanal Anabel , Guarner Carlos , Romero-Gomez Manuel , Muņoz-Yagüe Teresa , Salmerón Javier , Hidalgo Ramón
Published: November 2006

A chronic adverse reaction may occur in some instances of drug-induced liver injury (DILI), even despite drug cessation. In our study, we obtained records from a Spanish registry and evaluated cases of DILI with biochemical evidence of long-term damage. Chronic outcome was defined as a persistent biochemical abnormality of hepatocellular pattern of damage more than 3 months after drug withdrawal or more than 6 months after cholestatic/mixed damage. Data on 28 patients with a chronic clinical evolution (mean follow-up 20 months) between November 1995 and October 2005 were retrieved (18 female; overall mean age 55 yr) and accounted for 5.7% of total idiosyncratic DILI cases (n = 493) submitted to the registry. The main drug classes were cardiovascular and central nervous system (28.5% and 25%, respectively), which, in contrast, represented only 9.8% and 13%, respectively, of all DILI cases. The most frequent causative drugs were amoxicillin–clavulanate (4 of 69 cases), bentazepam (3 of 7 cases), atorvastatin (2 of 7 cases), and captopril (2 of 5 cases). Patients with cholestatic/mixed injury (18 of 194 cases [9%]) were more prone to chronicity than patients with hepatocellular injury (10 of 240 cases;

P

< .031). In the case of chronic hepatocellular injury, 3 patients progressed to cirrhosis and 2 to chronic hepatitis. In the cholestatic/mixed group, liver biopsy indicated cirrhosis in 1 patient and ductal lesions in 3 patients.

In conclusion

, cholestatic/mixed type of damage is more prone to become chronic while, in the hepatocellular pattern, the severity is greater. Cardiovascular and central nervous system drugs are the main groups leading to chronic liver damage.
Ethical considerations in international research collaboration: The Bucharest early intervention project
Authors: ZEANAH CHARLES H. , KOGA SEBASTIAN F. , SIMION BOGDAN , STANESCU ALIN , TABACARU CRISTIAN L. , FOX NATHAN A. , NELSON CHARLES A. ,   BEIP CORE GROUP
Published: November 2006

The Bucharest Early Intervention Project (BEIP) is the first ever randomized controlled trial of foster care as an alternative to institutional care for young children. It involved a collaboration between American investigators and Romanian health and child protection professionals. We present a brief description of the Romanian context and the project itself before discussing a number of ethical issues raised by the project. Organized around a discussion of exploitation, risk/benefit ratio, and cultural sensitivity, we evaluate a number of ethical issues involved in the BEIP using the Ethical Clinical Research Framework and the Fair Benefits Framework. Based on this review, we conclude that notwithstanding challenging ethical dilemmas, the benefits of the project outweighed its risks. Throughout the planning and implementation of the project, ethical issues were a central focus of discussion among the investigators and in the collaboration between Americans and Romanians. Thoughtful discussions from multiple perspectives are necessary to conduct research that is ethically sound and scientifically meaningful.
Slot drainage of clay soils under sugarcane in Cuba
Authors: Vidal Luciano , Cairo Pedro , Menning Peter , Könker Hermann , Alonso Norberto , Gutierrez Arnaldo
Published: November 2006

To perform agricultural drainage of clay soils under sugarcane monoculture, a new kind of slot drainage was developed. A special implement produces slots of approximately 6 cm width and 95 cm depth, which are filled with crumbly soil substrate. After heavy rain, a large amount of water will be discharged very quickly through these slots. Under the economic conditions of Cuba, slot drainage pays for itself within 3–5 years. Furthermore, time periods of inhibited harvesting machine operation are cut short, enabling sugar factories to operate with fewer interruptions. Copyright © 2006 John Wiley & Sons, Ltd.
Anodic oxidation and hydrothermal treatment of commercially pure titanium surfaces increases expression of bone morphogenetic protein‐2 in the adherent macrophage cell line J774A.1
Authors: Takebe J. , Ito S. , Champagne C.M. , Cooper L.F. , Ishibashi K.
Published: November 2006

The surface property of commercially pure titanium (cpTi) was improved by forming a thin hydroxyapatite (HA) layer by anodic oxidation and hydrothermal treatment (HA/cpTi). We hypothesize that the adhesion of macrophages to HA/cpTi surfaces is important to the process of osseointegration. This study investigates the effect of adhesion of macrophages to HA/cpTi surfaces on the expression of bone morphogenetic protein‐2 (BMP‐2). The murine macrophage cell line J774A.1 was cultured on HA/cpTi and polished cpTi (S/cpTi). Macrophage cell adhesion was examined by SEM, 0–72 h following plating onto HA/cpTi and S/cpTi. BMP‐2 gene expression was examined by RT‐PCR analysis. The level of BMP‐2 secreted into the supernatant was measured using an ELISA assay. The extent of macrophage adhesion increased with time on both the HA/cpTi and S/cpTi surfaces, with a“ higher degree of spreading observed on HA/cpTi than onS/cpTi surfaces after 24 or 72 h. The ratio of BMP‐2 mRNA was higher on HA/cpTi than on S/cpTi after 24 h (0.348 vs. 0, p < 0.05) and 72 h (0.584 vs. 0.189, p < 0.05). After 24 h, secretion of BMP‐2 was detected in cultures grown on HA/cpTi, but not on S/cpTi. After 72 h, secretion of BMP‐2 was detected in cultures grown on S/cpTi, but the levels were higher in cultures grown on HA/cpTi. These findings show that macrophages have the capacity to adhere to HA/cpTi endosseous implants and provide a source of osteoinductive cytokines that may play a key role in the process of osseointegration. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Quantification of fibrinogen adsorption onto 316L stainless steel
Authors: Gettens Robert T.T. , Gilbert Jeremy L.
Published: November 2006

Adsorption of the plasma protein fibrinogen (Fb) onto 316L stainless steel (316L SS) was observed and quantified using both in situ and ex situ atomic force microscopy techniques. Industry standard mechanical and electrochemical polishing techniques were used to prepare bulk alloy 316L SS samples, rendering the surfaces flat enough to directly observe and measure Fb adsorption. The data were analyzed kinetically using a Langmuir model. Largely irreversible adsorption was found on the 316L SS surface with an adsorption rate constant (ko) of 1.9 × 10−4 mL μg−1 s−1 using the ex situ method and 1.7 × 10−4 mL μg−1 s−1 using the in situ method. Additionally, protein conformation and assembly orientation on these surfaces were documented, where the adsorption pattern appeared random. Complete area coverage was never obtained. That is, after adsorption for over 5 time constants (5τ), voids in the structure were always observed. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Calcium phosphate bone cements, functionalized with VEGF: Release kinetics and biological activity
Authors: Lode A. , Wolf‐Brandstetter C. , Reinstorf A. , Bernhardt A. , König U. , Pompe W. , Gelinsky M.
Published: November 2006

Calcium phosphate bone cements are of great interest for bone replacement since the nanocrystalline structure allows their remodelling into native bone tissue. A strategy to accelerate vascularization of the implant region is the functionalization with vascular endothelial growth factor (VEGF), which is known to mediate angiogenesis in vivo. In this study, the release of recombinant human VEGF (rhVEGF165) following physical adsorption to Biocement D (BioD) and several modifications were investigated. Our data demonstrate a high VEGF binding capacity of BioD and a sustained release with a moderate initial burst. A proliferation assay using endothelial cells revealed maintenance of biological activity of VEGF after release from BioD. Release behavior of BioD was not improved by modification with mineralized collagen type I, as well as with a combination of mineralized collagen with O‐phospho‐L‐serine and sodium citrate, respectively. In contrast, a positive impact of these modifications on the activity of released VEGF was observed; in case of the phosphoserine‐ and sodium citrate‐modified cements, the biological efficacy of released VEGF was even higher than that of nonreleased control VEGF. We conclude that the bone implant material BioD and, especially, the phosphoserine modification may support activation of angiogenesis by delivery of VEGF in a local and sustained manner. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Lamins of ocular lens epithelial cells
Authors: Bagchi M. , Petrov T. , Maisel H.
Published: November 2006

Experiments were performed to characterize a prominent nuclear matrix (NM) protein isolated from tissue cultured mouse lens epithelial cells. This NM protein was separated by SDS‐PAGE and the stained gel band was analyzed by mass spectroscopy. Blast analysis of the amino acid sequence derived by mass spectroscopy revealed the presence of Lamin C in the NM of the mouse lens epithelial cells. We also examined nuclear proteins of adult and fetal human lenses. Data collected from these experiments showed the presence of Lamin C in both adult and fetal lens cells. However fetal lens cells only show Lamin C dimers, whereas adult human lens contained dimers, monomers and degraded Lamin C. Early and late passaged tissue cultured mouse lens epithelial cells also contained Lamin C in the nucleus with a preponderance of the dimer in the early passaged cells. The biological significance of the presence of dimers in human fetal lens cells and early passaged mouse lens cells is not known. However, it could suggest an enhanced docking capability of Lamin C dimers for other physiologically important nuclear proteins. J. Cell. Biochem. 100: 923–928, 2007. © 2006 Wiley‐Liss, Inc.
The transcription factor KLF11 can induce γ‐globin gene expression in the setting of in vivo adult erythropoiesis
Authors: Emery David W. , Gavriilidis Georgios , Asano Haruhiko , Stamatoyannopoulos George
Published: November 2006

Previous studies in a fetal erythroid cell line demonstrated that the transcription factor, Krüppel‐like factor 11 (KLF11), could specifically induce transcription from a γ‐globin gene promoter, and that this induction was mediated through a specific canonical CACCC cis‐DNA binding motif. We report here that ectopic expression of KLF11 can also induce fetal γ‐globin gene expression in the setting of adult erythropoiesis both in vitro and in vivo. Studies in an adult‐stage murine erythroleukemia (MEL) cell line demonstrated that retrovirus vector‐mediated transduction of KLF11 could increase both the amount of expression from a basally active, but not from a overtly silenced, recombinant γ‐globin transgene, as well as the frequency of cells expressing this transgene. A similar pattern of γ‐globin gene induction was also observed both in vitro and in vivo following KLF11 transduction of bone marrow from mice containing a basally active γ‐globin transgene. These studies provide the first evidence that ectopic expression of a transcription factor can induce γ‐globin gene expression in vivo during adult erythropoiesis. J. Cell. Biochem. 100: 1045–1055, 2007. © 2006 Wiley‐Liss, Inc.
The role of noggin in human mesenchymal stem cell differentiation
Authors: Rifas Leonard
Published: November 2006

Noggin is a secreted protein that inhibits the binding of bone morphogenetic proteins (BMPs) to their cognate receptor. Its role in human mesenchymal stem cell differentiation has not been well studied. Here, we studied the effect of noggin on human mesenchymal stem cell differentiation induced by inflammatory cytokines (activated T‐cell conditioned medium (ACTTCM) or the combination of four T‐cell cytokines, TNF‐α, TGF‐β, IFN‐γ, and IL‐17 (TTII)), BMPs, or dexamthasone (DEX). HMSC treated with TTII alone rapidly induced alkaline phosphatase (AlkP) activity. Inclusion of noggin resulted in an additive effect. Noggin acted additively with DEX to induce a significantly higher level of AlkP induction than either noggin or DEX alone. Noggin was examined for its ability to inhibit mineralization in long‐term cultures of HMSC stimulated with BMP‐2, BMP‐6, BMP‐7, DEX, or TTII. Surprisingly, noggin alone induced mineralization while it did not inhibit mineralization induced by TTII or BMP‐2, BMP‐6, or BMP‐7. Interestingly, when HMSC were treated with both noggin and DEX they acted synergistically to induce mineralization nearly 3‐fold over DEX alone and 30‐fold over noggin alone. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis showed that T‐cell cytokines induced noggin, Runx2, BMP‐2, and osteocalcin gene expression, while noggin alone induced BMP‐2 and osteocalcin gene expression, but not Runx2, although it increased the expression of ActRII, a receptor for BMP‐2. These results suggest that in HMSC, the anabolic action of inflammation on bone formation occurs through the induction of noggin, which then induces BMP‐2 receptor and BMP‐2 leading to the activation of the differentiation process. J. Cell. Biochem. 100: 824–834, 2007. © 2006 Wiley‐Liss, Inc.
Exposure to terrorism and violent behavior among adolescents in Israel
Authors: Even‐Chen Merav Solomon , Itzhaky Haya
Published: November 2006

It is commonly assumed that exposure to terrorism may lead to violent behavior, but there is little empirical research on the relationship between these two variables. In the present paper, we examined the extent to which exposure to terrorism contributes to violent behavior among adolescents. In addition, we considered the role of environmental factors ( domestic and community violence) and personal and environmental resources (family and social support, mastery, hope, and life satisfaction). Two hundred and fifty‐four Israeli adolescents residing in areas with different levels of exposure to terrorism completed questionnaires. The findings confirm that exposure to terrorism contributes significantly to violent behavior. Exposure to domestic and community violence and mastery also contributed to explaining the variance in violent behavior, whereas the effects of hope and life satisfaction were indirect, and were expressed only in an interaction with variables of exposure to terrorism. The findings may be helpful in identifying groups at risk for violent behavior, as well as in guiding professionals to moderate and prevent such behavior. The findings also emphasize the impact of security‐related stress situations and prolonged exposure to terrorism on manifestations of violence. © 2007 Wiley Periodicals, Inc.
Choosing to belong: The influence of choice on social identification and psychological sense of community
Authors: Obst Patricia L. , White Katherine M.
Published: November 2006

The influence of choice on individuals' social identification and psychological sense of community (PSOC) with their group memberships is a seldom examined area. The current study examined participants' (N = 219) level of social identification and PSOC across multiple group memberships that differ in the degree of choice associated with membership. In addition, consideration was given to the influence of contextual salience on the relationship between choice and social identification and PSOC. Results indicated that, controlling for contextual salience, choice was positively associated with levels of social identification and PSOC. © 2007 Wiley Periodicals, Inc.
Quantization of widefield fluorescence images using structured illumination and image analysis software
Authors: Barlow Andrew L. , Guerin Christopher J.
Published: November 2006

It is difficult to obtain precise quantitative measurements from fluorescent images captured from widefield microscopes. We wished to ascertain if reliable quantitative measurements of both biological and nonbiological specimens were possible using a widefield microscope equipped with a structured illumination system and image analysis software. In a nonbiological specimen, images were obtained from fluorescent beads of known intensity. For a biologically relevant model we used the uptake of fluorescently labeled transferrin by HeLa cells in culture. In the bead sample, the mean intensity of beads acquired with the structured illumination system showed relative intensities near to the predicted values without any further manipulation of data. In the transferrin uptake experiments, uptake and subsequent recycling of the labeled transferrin could be accurately and reproducibly measured. We conclude that using a combination of structured illumination and image processing algorithms accurate quantization of fluorescent images can be achieved in widefield microscopyMicrosc. Res. Tech., 2007. © 2006 Wiley‐Liss, Inc.
User‐friendly semiautomated assembly of accurate image mosaics in microscopy
Authors: Thévenaz Philippe , Unser Michael
Published: November 2006

We present a semiautomated software solution to the problem of extending the lateral field of view of a classical microscope. The initial requirements are a set of overlapping images, along with their user‐provided coarse mosaic. Our solution then refines this initial mosaic in a fully automatic fashion. We rely on a highly accurate registration engine to perform the pairwise registration of the individual images, and on an efficient strategy to minimize the amount of computations while maintaining the highest possible global quality. We describe these ingredients, which we make available as a free multiplatform user‐friendly software package. We also highlight why and how the specific aspects of the present microscopy application differ from those encountered while creating more common mosaics such as panoramas. Finally, we present experimental results that illustrate and validate our method on a real biological sample. We conclude by showing that we are able to reach subpixel accuracy. Microsc. Res. Tech., 2007. © 2006 Wiley‐Liss, Inc.
Restituting intestinal epithelial cells exhibit increased transducibility by adenoviral vectors
Authors: Kesisoglou Filippos , Schmiedlin‐Ren Phyllissa , Fleisher David , Roessler Blake , Zimmermann Ellen M.
Published: November 2006

Background and aims

While mature enterocytes are resistant to transduction by adenovirus type 5 (Ad5) vectors, undifferentiated cells are transduced much more efficiently. Our purpose was to study enterocyte transduction in models of intestinal wound healing.

Methods

Transduction was studied ex vivo using cultures of endoscopic biopsies and in vitro utilizing Caco‐2 cells in models of mucosal wound healing. Vectors carried either the LacZ or the luciferase gene. CAR (coxsackievirus and adenovirus receptor) and integrins were studied with transduction inhibition and immunofluorescent staining.

Results

Increased transduction efficiency was observed for a subset of enterocytes with a flattened de‐differentiated phenotype present at the edge of cultured biopsies. In the in vitro systems, expanding Caco‐2 cell monolayers exhibited increased transducibility that was time‐ and dose‐dependent, reaching virtually 100% in cells along the leading edge at high viral load. Bioluminescence activity of transduced expanding monolayers was up to 3‐fold greater than that of non‐expanding monolayers (‘fence’ system, 48 h, MOI 1000, p < 0.05). Mitomycin C pre‐treatment did not affect levels of transduction in expanding monolayers. At the highest viral load tested, CAR or integrin blocking prior to virus application resulted in 39.4% and 45.4% reduction in transduction levels (p < 0.05). Immunofluorescence revealed altered expression of CAR on the migrating edge of the Caco‐2 cultures and the expression of CAR on the apical membrane of biopsy enterocytes.

Conclusions

Increased CAR and integrin accessibility in migrating enterocytes mediates increased transduction by Ad5 vectors. This subset of enterocytes provides a target for the delivery of genes of interest for both research and gene therapy applications. Copyright © 2006 John Wiley & Sons, Ltd.
Excitotoxic protection by polyanionic polysaccharide: Evidence of a cell survival pathway involving AMPA receptor–MAPK Interactions
Authors: Chicoine Linda M. , Bahr Ben A.
Published: November 2006

Growing numbers of studies indicate that polysaccharides influence signaling events important for brain function. It has been speculated that such polysaccharide modulation of neuronal signals can promote synaptogenesis and cell maintenance. Here, we tested whether dextran sulfate, a polyanion that mimics natural mucopolysaccharides, protects hippocampal neurons against excitotoxic insults. An excitotoxin was applied to primary hippocampal cultures in the absence or presence of a large 500‐kDa dextran sulfate (DS‐L), a smaller 5–8‐kDa species (DS‐S), or sulfate‐free dextran of 500 kDa. Only DS‐L prevented neuronal damage as determined by a membrane permeability assay and phase contrast morphology. The sulfate and size dependence is also characteristic of DS‐L's modulatory action on the channel activity of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)‐type glutamate receptors. The extent of neuroprotection correlates with the level of modulation of AMPA responses, and DS‐L exhibits comparable EC50 values for the two effects (3–7 nM). DS‐L also modulates the link between AMPA receptors and mitogen‐activated protein kinase (MAPK) involving extracellular signal‐regulated protein kinase (ERK), well known for its involvement in cell survival and repair. Correspondingly, protection against N‐methyl‐D‐aspartate (NMDA) excitotoxicity was evident in hippocampal slice cultures when DS‐L was applied 30 min postinsult. These findings suggest that polysaccharides elicit neuroprotection in the brain, including enhanced repair responses through the AMPA receptor‐MAPK axis. © 2006 Wiley‐Liss, Inc.
Neuroprotective effect of 17β‐estradiol against N‐methyl‐D‐aspartate‐induced retinal neurotoxicity via p‐ERK induction
Authors: Hayashi Yasuhiro , Kitaoka Yasushi , Munemasa Yasunari , Ohtani‐Kaneko Ritsuko , Kikusui Takefumi , Uematsu Akira , Takeda Hiroyuki , Hirata Kazuaki , Mori Yuji , Ueno Satoki
Published: November 2006

We investigated whether the neuroprotective effect of estrogen is mediated by the estrogen receptor (ER) and whether extracellular signal‐regulated kinase (ERK) is involved in the protective effect of estrogen against N‐methyl‐D‐aspartate (NMDA)‐induced retinal neurotoxicity. Retrograde labeling of retinal ganglion cells (RGCs) showed that pretreatment with 17β‐estradiol (E2) using a silastic implant significantly attenuated the loss of RGCs induced by intravitreal injection of NMDA. Simultaneous administration of U0126, an ERK inhibitor, with NMDA completely abolished the protective effect of E2. Moreover, ICI182,780, an ER antagonist, also significantly diminished the protective effect of E2. Pretreatment with E2 significantly reduced the number of terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL)‐positive cells in the retinal ganglion cell layer (RGCL) and the inner nuclear layer (INL) 12 hr after NMDA injection. Moreover, ICI182,780 inhibited the ameliorative effect of E2 on TUNEL‐positive cells in a dose‐dependent manner. Immunostaining of anti‐ERα monoclonal antibody was observed mainly in the RGCL and the INL. Western blot analysis showed a significant increase in the level of phosphorylated ERK (p‐ERK) 6 hr after NMDA injection. However, NMDA did not increase the level of p‐ERK protein 7 days after injection. Pretreatment of E2 induced further increases of p‐ERK expression 6 hr and 7 days after NMDA injection, and U0126 and ICI182,780 significantly inhibited E2‐induced p‐ERK expression after 6 hr. These results suggest that E2 has an ER‐mediated neuroprotective effect against NMDA‐induced retinal neurotoxicity and that this effect may be associated with induction of p‐ERK in the retina. © 2006 Wiley‐Liss, Inc.
Oxidative stress in the aging murine olfactory bulb: Redox proteomics and cellular localization
Authors: Vaishnav Radhika A. , Getchell Marilyn L. , Poon H. Fai , Barnett Kara R. , Hunter Samuel A. , Pierce William M. , Klein Jon B. , Butterfield D. Allan , Getchell Thomas V.
Published: November 2006

A recent proteomics analysis from our laboratory demonstrated that several oxidative stress response proteins showed significant changes in steady‐state levels in olfactory bulbs (OBs) of 20‐ vs. 1.5‐month‐old mice. Oxidative stress may result in protein oxidation. In this study, we investigated two forms of protein oxidative modification in murine OBs: carbonylation and nitration. Redox proteomics with two‐dimensional gel electrophoresis, Western blotting, protein digestion, and mass spectrometry was used to quantify total and specific protein carbonylation and to identify differentially carbonylated proteins and determine the carbonylation status of previously identified proteins in OBs of 1.5‐ and 20‐month‐old mice. Immunohistochemistry was used to demonstrate the relative intensity and localization of protein nitration in OBs of 1.5‐, 6‐, and 20‐month‐old mice. Total protein carbonylation was significantly greater in OBs of 20‐ vs. 1.5‐month‐old mice. Aldolase 1 (ALDO1) showed significantly more carbonylation in OBs from 20‐ vs. 1.5‐month‐old mice; heat shock protein 9A and dihydropyrimidinase‐like 2 showed significantly less. Several previously investigated proteins were also carbonylated, including ferritin heavy chain (FTH). Nitration, identified by 3‐nitrotyrosine immunoreactivity, was least abundant at 1.5 months, intermediate at 6 months, and greatest at 20 months and was localized primarily in blood vessels. Proteins that were specific targets of oxidation were also localized: ALDO1 in astrocytes of the granule cell layer and FTH in mitral/tufted cells. These results indicate that specific carbonylated proteins, including those in astrocytes and mitral/tufted neurons, and nitrated proteins in the vasculature are molecular substrates of age‐related olfactory dysfunction. © 2006 Wiley‐Liss, Inc.
Changes of amino acid concentrations in the rat vestibular nuclei after inferior cerebellar peduncle transection
Authors: Sun Yizhe , Godfrey Donald A. , Godfrey Timothy G. , Rubin Allan M.
Published: November 2006

Although there is a close relationship between the vestibular nuclear complex (VNC) and the cerebellum, little is known about the contribution of cerebellar inputs to amino acid neurotransmission in the VNC. Microdissection of freeze‐dried brain sections and high‐performance liquid chromatography (HPLC) were combined to measure changes of amino acid concentrations within the VNC of rats following transection of the cerebellovestibular connections in the inferior cerebellar peduncle. Distributions of 12 amino acids within the VNC at 2, 4, 7, and 30 days after surgery were compared with those for control and sham‐lesioned rats. Concentrations of γ‐aminobutyric acid (GABA) decreased by 2 days after unilateral peduncle transection in nearly all VNC regions on the lesioned side and to lesser extents on the unlesioned side and showed partial recovery up to 30 days postsurgery. Asymmetries between the two sides of the VNC were maintained through 30 days. Glutamate concentrations were reduced bilaterally in virtually all regions of the VNC by 2 days and showed complete recovery in most VNC regions by 30 days. Glutamine concentrations increased, starting 2 days after surgery, especially on the lesioned side, so that there was asymmetry generally opposite that of glutamate. Concentrations of taurine, aspartate, and glycine also underwent partially reversible changes after peduncle transection. The results suggest that GABA and glutamate are prominent neurotransmitters in bilateral projections from the cerebellum to the VNC and that amino acid metabolism in the VNC is strongly influenced by its cerebellar connections. © 2006 Wiley‐Liss, Inc.
Enhanced autophagic cell death in expanded polyhistidine variants of HOXA1 reduces PBX1‐coupled transcriptional activity and inhibits neuronal differentiation
Authors: Paraguison Rubigilda C. , Higaki Katsumi , Yamamoto Kenji , Matsumoto Hideo , Sasaki Tsukasa , Kato Nobumasa , Nanba Eiji
Published: November 2006

HOXA1 is a member of the homeobox gene family and is involved in early brain development. In our previous study, we identified novel variants of polyhistidine repeat tract in HOXA1 gene and showed that ectopic expression of expanded variants led to enhanced intranuclear aggregation and accelerated cell death in a time‐dependent manner. Here, we further investigate the implications of polyhistidine variants on HOXA1 function. Aside from intranuclear aggregation, we observed cytosolic aggregates during the early stages of expression. Rapamycin, an autophagy inducer, resulted in decreased protein aggregation and cell death. Here, we also show an interaction between variants of HOXA1 and one of the HOX protein known cofactors, PBX1. Expanded HOXA1 variants exhibited reduced PBX1‐coupled transcriptional activity through a regulatory enhancer of HOXB1. Moreover, we demonstrate that both deleted and expanded variants inhibited neurite outgrowth in retinoic acid‐induced neuronal differentiation in neuroblastoma cells. These results provide further evidence that expanded polyhistidine repeats in HOXA1 enhance aggregation and cell death, resulting in impaired neuronal differentiation and cooperative binding with PBX1. © 2006 Wiley‐Liss, Inc.
Compensation by reduced L‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor responses in a mouse model with reduced γ‐aminobutyric acid type A receptor‐mediated synaptic inhibition
Authors: Möykkynen Tommi P. , Sinkkonen Saku T. , Korpi Esa R.
Published: November 2006

L‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonists increase the threshold for electroshock‐induced convulsions. Here, we show that a transgenic mouse line overexpressing cerebellum‐restricted γ‐aminobutyric acid type A (GABAA) receptor α6 subunit in the hippocampal CA1 pyramidal cells (Thy1α6 mouse line) exhibits about a 20% increase in the electroshock current intensity inducing tonic hindlimb extension convulsion in 50% of the mice compared with that of their wild‐type controls. AMPA receptor‐mediated miniature excitatory postsynaptic currents (mEPSCs) in patch clamp recordings of CA1 pyramidal neurons in hippocampal slices had decreased amplitudes (8.4 ± 2.2 pA) in the transgenics compared with the wild types (10.3 ± 2.5 pA) but showed no change in current decay or frequency. Our results suggest that decreased AMPA‐mediated neurotransmission might explain the increased threshold for electroconvulsions and warrant further studies on the regulation between various components of inhibition and excitation in neurons. © 2006 Wiley‐Liss, Inc.
Current approaches to medullary thyroid carcinoma, sporadic and familial
Authors: Fialkowski Elizabeth A. , Moley Jeffrey F.
Published: November 2006

Medullary thyroid carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs in hereditary (25% of cases) and sporadic forms, and aggressiveness is related to the clinical presentation (hereditary vs. sporadic) and the type of RET mutation present. In hereditary cases, early diagnosis makes preventative surgery possible. In established cases, thorough surgical extirpation of the primary tumor and nodal metastases has been the mainstay of treatment. Radioactive iodine, external beam radiation therapy (EBRT), and conventional chemotherapy have not been effective. Newer systemic treatments, with agents that target abnormal RET proteins, hold promise and are being tested in clinical trials for patients with metastatic disease. J. Surg. Oncol. 2006;94:737–747. © 2006 Wiley‐Liss, Inc.
PDMS‐Modified Polyurethane Films with Low Water Contact Angle Hysteresis
Authors: Dou Qizheng , Wang Changchun , Cheng Cheng , Han Wei , Thüne Peter C. , Ming Weihua
Published: November 2006

Summary: Polyurethane (PU) films with low water contact angle hysteresis (CAH) were prepared by employing less than 0.2 wt.‐% of mono‐ or bihydroxyl‐functionalized polydimethylsiloxane (PDMS) of 60–70 DMS repeat units. A Si content of as low as 0.03 wt.‐% was sufficient to lead to a CAH of 20°. The curing temperature demonstrated strong effects on the wetting behavior of the PDMS‐modified PU films: a relatively low curing temperature (40 °C) resulted in stronger surface segregation of PDMS than higher curing temperatures, giving rise to high water receding CAs and thus low CAH. It was found from angle‐resolved X‐ray photoelectron spectroscopy analysis that the surface silicon content was greater when cured at a lower temperature. The surface of PDMS‐modified PU films was very smooth from AFM observations, but the Si content had strong effects on the surface phase contrast. The chain length of 60–70 DMS repeating units for both mono‐ and bifunctional PDMS appeared to be long enough to prevent the surface reorganization during the CA measurements.

Schematic, simplified illustration of PDMS chains at the surface of PU films modified by PDMS60OH and PDMS70(OH)2.

magnified image

Schematic, simplified illustration of PDMS chains at the surface of PU films modified by PDMS60OH and PDMS70(OH)2.
Structure and Properties of Poly(ε‐caprolactone) Networks with Modulated Water Uptake
Authors: Escobar Ivirico Jorge L. , Salmerón Sánchez Manuel , Sabater i Serra Roser , Meseguer Dueñas José María , Gómez Ribelles José Luis , Monleón Pradas Manuel
Published: November 2006

Summary: A PCL macromonomer was obtained by the reaction of PCL diol with methacrylic anhydride. The effective incorporation of the polymerizable end groups was assessed by FT‐IR and 1H NMR spectroscopy. PCL networks were then prepared by photopolymerization of the PCL macromonomer. Furthermore, the macromonomer was copolymerized with HEA, with the aim of tailoring the hydrophilicity of the system. A set of hydrophilic semicrystalline copolymer networks were obtained. The phase microstructure of the new system and the network architecture was investigated by DSC, IR, DMS, TG, dielectric spectroscopy and water sorption studies. The presence of the hydrophilic units in the system prevented PCL crystallization on cooling; yet there was no effect on the glass transition process. The copolymer networks showed microphase separation and the α relaxation of the HEA units moved to lower temperatures as the amount of PCL in the system increased.

Ideal structure, compatible with the experimental results, for the hydrophilized poly(ε‐caprolactone) networks with modulated water uptake.

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Ideal structure, compatible with the experimental results, for the hydrophilized poly(ε‐caprolactone) networks with modulated water uptake.
Asynchronous blepharospasm, facial and cervical dystonia, and bilateral asynchronous hemifacial spasm
Authors: Katz Bradley J. , Burroughs John R. , Anderson Richard L. , Bownds Shannon , McCann John D.
Published: November 2006

We present a patient with a facial movement disorder that has characteristics of both blepharospasm and bilateral asynchronous hemifacial spasm. Because of the increased incidence of blepharospasm in patients with hemifacial spasm, our patient's clinical presentation is probably not a chance occurrence, but rather a manifestation of some predisposition for these two movement disorders. This unusual constellation of signs and symptoms challenges the current diagnostic criteria and suggests that some of these facial movement disorders may lie on a spectrum, rather than represent distinct entities. © 2006 Movement Disorder Society
Pyramidal tract degeneration in multiple system atrophy: The relevance of magnetization transfer imaging
Authors: da Rocha Antonio José , Maia Antonio Carlos Martins , da Silva Carlos Jorge , Braga Flávio Túlio , Ferreira Nelson Paes Diniz Fortes , Barsottini Orlando Graziani Povoas , Ferraz Henrique Ballalai
Published: November 2006

The clinical features of multiple system atrophy (MSA) include four domains: autonomic failure/urinary dysfunction, Parkinsonism, cerebellar ataxia, and corticospinal tract dysfunction. Although the diagnosis of definite MSA requires pathological confirmation, magnetic resonance imaging (MRI) studies have been shown to contribute to the diagnosis of MSA. Although pyramidal tract dysfunction is frequent in MSA patients, signs of pyramidal tract involvement are controversially demonstrated by MRI. We evaluated the pyramidal involvement in 10 patients (7 women) with clinically probable MSA, detecting the presence of spasticity, hyperreflexia, and Babinski sign, as well as demonstrating degeneration of the pyramidal tract and primary motor cortex by MRI in all of them. Our article also discusses key radiological features of this syndrome. In MSA, pyramidal tract involvement seems to be more frequent than previously thought, and the clinicoradiological correlation between pyramidal tract dysfunction and degeneration may contribute to the understanding of the clinical hallmarks of MSA. MRI may also add information regarding the differential diagnosis of this syndrome. © 2006 Movement Disorder Society
Lower urinary tract symptoms and bladder control in advanced Parkinson's disease: Effects of deep brain stimulation in the subthalamic nucleus
Authors: Winge Kristian , Nielsen Kurt Krøyer , Stimpel Hans , Lokkegaard Annemette , Jensen Steen Rusborg , Werdelin Lene
Published: November 2006

Deep brain stimulation in the subthalamic nucleus (STN) leads to significant improvement in motor function in patients with advanced Parkinson's disease (PD). In this prospective study including 16 patients with PD, we investigated (1) lower urinary tract symptoms (LUTS) by questionnaires International Prostate Symptom Score (IPSS, symptoms only) and Danish Prostate Symptom Score (DanPSS, symptoms and bother of symptoms) and (2) bladder control (assessed by urodynamics) before and after implantation of electrodes in the STN. PD symptoms (Unified Parkinson's Disease Rating Scale score) improved significantly (P < 0.0001), and symptoms of overactive bladder (IPSS) decreased along with the troublesome symptoms of overactive bladder (DanPSS; P < 0.01 for both). Urodynamic parameters before and after implantation of electrodes in the STN, evaluated with and without the stimulation on, did not change significantly. © 2006 Movement Disorder Society
Efficacy of pramipexole in restless legs syndrome: A six‐week, multicenter, randomized, double‐blind study (effect‐RLS study)
Authors: Oertel Wolfgang H. , Stiasny‐Kolster Karin , Bergtholdt Bettina , Hallström Yngve , Albo Jaan , Leissner Lena , Schindler Thomas , Koester Juergen , Reess Juergen
Published: November 2006

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions‐Improvement (CGI‐I) assessments of “much/very much improved” (CGI‐I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (±SE) in IRLS score were 5.7 (±0.9) for placebo (median dose 0.47 mg/day) and 12.3 (±0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI‐I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study. © 2006 Movement Disorder Society
Well‐posedness for the incompressible magneto‐hydrodynamic system
Authors: Miao Changxing , Yuan Baoquan , Zhang Bo
Published: November 2006

This paper is concerned with well‐posedness of the incompressible magneto‐hydrodynamics (MHD) system. In particular, we prove the existence of a global mild solution in BMO−1 for small data which is also unique in the space C([0, ∞); BMO−1). We also establish the existence of a local mild solution in bmo−1 for small data and its uniqueness in C([0, T); bmo−1). In establishing our results an important role is played by the continuity of the bilinear form which was proved previously by Kock and Tataru. In this paper, we give a new proof of this result by using the weighted Lp‐boundedness of the maximal function. Copyright © 2006 John Wiley & Sons, Ltd.
Individual learning and building organisational capacity for development
Authors: Johnson Hazel , Thomas Alan
Published: November 2006

Building capacities and capabilities for international development is an ongoing subject for debate, further fuelled by recent interest in learning and knowledge. This article focuses on how, and the extent to which, individual learners in education and training programmes for development policy and management interact with their organisations to build capacities and capabilities. It demonstrates some of the ways that individual learning and organisational capacity are linked by examining case studies from Uganda, Zimbabwe and South Africa. The article reflects on the complex nature of this interaction and on the broader challenges of linking learning to development. Copyright © 2006 John Wiley & Sons, Ltd.
Single nucleotide polymorphisms of tumor necrosis factor‐α and the susceptibility to bronchopulmonary dysplasia
Authors: Strassberg Sonya S. , Cristea Ioana A. , Qian Dajun , Parton Lance A.
Published: November 2006

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. A “New” BPD has been characterized in preterm infants that may begin in utero, and then progress post‐natally, resulting in arrested lung development and alveolar hypoplasia. Foundations for this “New” BPD may be derived from pro‐inflammatory genes including tumor necrosis factor‐α (TNFα). The hypothesis of the current study is that single nucleotide polymorphisms (SNPs) of the pro‐inflammatory TNFα gene place preterm infants at increased risk for BPD. Preterm infants (105 in number) with birthweights ≤1 kg, who survived to at least 36 weeks postmenstrual age (PMA) or discharge were enrolled into this study. They were stratified for BPD according to their need for supplemental oxygen at 28 days and at 36 weeks PMA (non‐, mild‐, moderate‐, or severe‐BPD). DNA was extracted from these infants and subjected to analyses for the TNFα SNPs: −1,031, −863, −857, −308, and −238. The PHASE software (version 2.1) was used to reconstruct haplotypes and estimate their frequencies within the study population. Differences in birth weight (P < 0.001) and gestational age (P < 0.001), but not in racial distribution between the groups were found. Haplotype‐specific analysis revealed no significant association between BPD severity and any of the 5‐marker common haplotypes with 10 or more copies in this study population. Additionally, no significant association was observed in any three SNP haplotypes at −1,031, −863, and −857, and two SNP haplotypes at −308 and −238. We observed no association between BPD severity and the five TNFα SNPs investigated. Pediatr Pulmonol. 2007; 42:29–36. © 2006 Wiley‐Liss, Inc.
The effectiveness of a pre‐operative home‐based physiotherapy programme for chronic anterior cruciate ligament deficiency
Authors: Keays SL , Bullock‐Saxton JE , Newcombe P , Bullock MI
Published: November 2006

Background and Purpose. Little evidence supports the prescription of pre‐operative rehabilitation in the treatment of chronic anterior cruciate ligament‐deficient (ACLD) subjects. The aim of the present study was to assess the effectiveness of a specific six‐week pre‐operative exercise programme on ACLD knees. Method. A single, masked, controlled study was designed. This comprised two matched groups of 12 chronically ACLD patients awaiting reconstruction and a group of 12 matched uninjured control subjects. Only one ACLD group received a home‐based exercise and educational programme. Assessment before and after the exercise intervention included: knee joint stability (clinical and KT1000 evaluation); muscle strength (Cybex II); standing balance and functional performance (agility, hop and subjective tests). Results. At the time of initial assessment there were no statistically significant differences in any measures for the two ACLD groups but both ACLD groups were significantly different from the uninjured control group as regards quadriceps strength and function. Measures taken after six weeks showed no significant improvement in the untreated ACLD group or in the uninjured control group The treated ACLD group showed significant improvement in the following measures: quadriceps strength measured at 60° and 120° per second (p < 0.001); single leg standing balance with eyes closed (p < 0.001); instrumented passive stability at 20 lb (89N) force (p = 0.003); agility and subjective performance (p < 0.001). The incidence of unstable episodes had decreased in the treated ACLD group, reducing further damage to the joint. Conclusion. This study leaves little doubt that pre‐operative physiotherapy had a positive effect on motor function in ACLD subjects and should be prescribed routinely to maximize muscle stabilizing potential prior to reconstruction. Patients report improved stability and, in certain cases, may avoid surgery. The finding that exercise increased the passive stability of the joint was unexpected and requires further investigation. Copyright © 2006 John Wiley & Sons, Ltd.