bluuebunny/crossref_metadata_2025 huggingface dataset:
RUNX genes find a niche in stem cell biology
Authors: Appleford Peter J. , Woollard Alison
Published: June 2009

The RUNX family of transcriptional regulators are well conserved throughout the animal kingdom, from the simple nematode worm Caenorhabditis elegans to vertebrates. Interest in the RUNX genes emerged principally as a result of the finding that chromosomal translocations disrupting RUNX protein function are observed in a large number of patients suffering with acute myeloid leukemia (AML). In the 20 years that RUNX genes have been under investigation, they have emerged as central players in the control of developmental decisions between proliferation and differentiation in a wide variety of biological situations. This review focuses on recent data highlighting the roles of RUNX genes in stem cells and illustrates the diversity of processes in which the RUNX proteins play a critical role. In particular, we focus on the role of RUNX1 in hematopoietic stem cells (HSCs) and hair follicle stem cells (HFSCs) and the importance of the solo C. elegans RUNX factor rnt‐1 in stem cell proliferation in the worm. Observations in a variety of stem cell systems have developed to the point where useful comparisons can be made, from which guiding principles may emerge. J. Cell. Biochem. 108: 14–21, 2009. © 2009 Wiley‐Liss, Inc.
Thyroid hormones induce cell proliferation and survival in ovarian granulosa cells COV434
Authors: Verga Falzacappa Cecilia , Mangialardo Claudia , Patriarca Valentina , Bucci Barbara , Amendola Donatella , Raffa Salvatore , Torrisi Maria Rosaria , Silvestrini Giuliana , Ballanti Paola , Moriggi Giulia , Stigliano Antonio , Brunetti Ercole , Toscano Vincenzo , Misiti Silvia
Published: June 2009

Numerous evidences indicate that thyroid hormones exert an important role in the regulation of the reproductive system in the adult female. Although a clear demonstration of the thyroid–ovarian interaction is still lacking, it is conceivable that thyroid hormones might have a direct role in ovarian physiology via receptors in granulosa cells. In this study we analyzed if thyroid hormone treatment could affect cell proliferation and survival of COV434 cells. To this aim cell growth experiments and cell cycle analyses by flow cytometry were performed. Secondly the T3 survival action was tested by TUNEL assay and MD30 cleavage analysis. We showed that T3, and not T4, can protect ovarian granulosa cells COV434 from apoptosis, regulating cell cycle and growth in the same cells. The increase in cell growth resulted in an augmented percentage of the cells in the S phase and, in a reduction of the doubling time (18%). Subsequently apoptotic pathway induced by serum deprivation has been evaluated in the cells exposed or not to thyroid hormone treatment. The T3 treatment was able to remarkably counteract the apoptotic process. Even at the ultrastructural level there was an evident protective effect of T3 in the cells that, besides the maintenance of the original morphology and, the absence of basophilic cytoplasm, conserved normal junctional areas. Furthermore, the protective T3 effect evaluated by FACS analysis in the presence of a PI3K inhibitor revealed, as also confirmed by Western Blot on pAkt, that the PI3K pathway is crucial in T3 survival action. J. Cell. Physiol. 221: 242–253, 2009. © 2009 Wiley‐Liss, Inc
Orderly hematopoietic development of induced pluripotent stem cells via Flk‐1+ hemoangiogenic progenitors
Authors: Niwa Akira , Umeda Katsutsugu , Chang Hsi , Saito Megumu , Okita Keisuke , Takahashi Kazutoshi , Nakagawa Masato , Yamanaka Shinya , Nakahata Tatsutoshi , Heike Toshio
Published: June 2009

Induced pluripotent stem (iPS) cells, reprogrammed somatic cells with embryonic stem (ES) cell‐like characteristics, are generated by the introduction of combinations of specific transcription factors. Little is known about the differentiation of iPS cells in vitro. Here we demonstrate that murine iPS cells produce various hematopoietic cell lineages when incubated on a layer of OP9 stromal cells. During this differentiation, iPS cells went through an intermediate stage consisting of progenitor cells that were positive for the early mesodermal marker Flk‐1 and for the sequential expression of other genes that are associated with hematopoietic and endothelial development. Flk‐1+ cells differentiated into primitive and definitive hematopoietic cells, as well as into endothelial cells. Furthermore, Flk‐1+ populations contained common bilineage progenitors that could generate both hematopoietic and endothelial lineages from single cells. Our results demonstrate that iPS cell‐derived cells, like ES cells, can follow a similar hematopoietic route to that seen in normal embryogenesis. This finding highlights the potential use of iPS cells in clinical areas such as regenerative medicine, disease investigation, and drug screening. J. Cell. Physiol. 221: 367–377, 2009. © 2009 Wiley‐Liss, Inc.
Stem cell pluripotency: A cellular trait that depends on transcription factors, chromatin state and a checkpoint deficient cell cycle
Authors: Boheler Kenneth R.
Published: June 2009

Embryonic stem (ES) and induced pluripotent stem (iPS) cells self‐renew and are pluripotent. Differentiation of these cells can yield over 200 somatic cell types, making pluripotent cells an obvious source for regenerative medicine. Before the potential of these cells can be maximally harnessed for clinical applications, it will be necessary to understand the processes that maintain pluripotentiality and signal differentiation. Currently, three unique molecular properties distinguish pluripotent stem cells from somatic cells. These include a unique transcriptional hierarchy that sustains the pluripotent state during the process of self‐renewal; a poised epigenetic state that maintains chromatin in a form ready for rapid cell fate decisions; and a cell cycle characterized by an extremely short gap 1 (G1) phase and the near absence of normal somatic cell checkpoint controls. Recently, B‐MYB (MYBL2) was implicated in the gene regulation of two pluripotency factors and normal cell cycle progression. In this article, the three pluripotency properties and the potential role of B‐Myb to regulate these processes will be discussed. J. Cell. Physiol. 221: 10–17, 2009. © 2009 Wiley‐Liss, Inc
A convenient approach to the canthin‐4‐one ring system: Total synthesis of the alkaloids tuboflavine and norisotuboflavine
Authors: Puzik Andreas , Bracher Franz
Published: June 2009

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Canthin‐4‐one, as well as 5‐ and 6‐alkylcanthin‐4‐ones are readily available through reaction of 1‐acyl‐β‐carbolines with Bredereck's reagent or dimethylacetamide acetals in anhydrous DMF. The intermediate enaminoketones readily undergo cyclization to the canthin‐4‐ones. The alkaloids tuboflavine and norisotuboflavine were prepared following this methodology. J. Heterocyclic Chem., (2009).
Seasonality and spatial pattern of rainfall of Sri Lanka: Exploratory factor analysis
Authors: Wickramagamage P.
Published: June 2009

This analysis is based on monthly means of rainfall at a dense network of gauging stations in Sri Lanka. The mean monthly values of rainfall at 646 stations were used as variables to characterise the individual stations. These variables show a significant correlation among most of them. The highest correlations were found between months within the same meteorological season, with one exception. The exception is that of October which has a higher correlation with months of southwest monsoon (SWM) than with the inter‐monsoon (IM) months. The IM months and November have moderate values of correlation with the months of SWM. All three months of northeast monsoon (NEM) are strongly correlated and form a clearly defined group. This pattern of correlation can be explained in terms of the spatial distribution of rainfall of the 12 months. The strongly correlated months have a similar spatial pattern. This indicates that the number of distinct spatial modes of rainfall is less than 12. To discover these modes, principal component analysis (PCA) and factor analysis (FA) were applied on the data set. Of the two ordination methods, FA produced more easily interpretable results than PCA. The factor solution identified four spatiotemporal rainfall modes—weak southwest (SW) mode (March–April), strong SW mode (May–October), strong NEM mode (December–February) and mixed mode (November). These modes have strong similarity to the monthly rainfall surfaces created using the original data of the same periods. Copyright © 2009 Royal Meteorological Society
Survival After Liver Transplantation for Hepatocellular Carcinoma in the Model for End-Stage Liver Disease and Pre–Model for End-Stage Liver Disease Eras and the Independent Impact of Hepatitis C Virus
Authors: Thuluvath Paul J. , Maheshwari Anurag , Thuluvath Nimisha P. , Nguyen Geoffrey C. , Segev Dorry L.
Published: June 2009

Abstract

It has been suggested that hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC) may have worse outcomes after liver transplantation (LT) because of more aggressive tumor biology. In this study, we determined the post-LT survival of HCC patients with and without HCV using United Network for Organ Sharing data from January 1994 to March 2008. Patients with HCC were stratified into HCV (HCC-HCV) and non-HCV (HCC–non-HCV) groups. In the era before the Model for End-Stage Liver Disease (MELD), there were 1237 HCC patients (780, HCV; 373, non-HCV; 84, unknown HCV status), and during the MELD era, there were 4933 HCC patients (3272, HCV; 1348, non-HCV; 313, unknown). In the pre-MELD era, 5-year graft (58.6% versus 53.7%) and patient (61.7% versus 59.3%) survival rates were marginally higher for HCC–non-HCV patients than for HCC-HCV patients. In the MELD era also, 5-year graft (61.2% versus 55.5%) and patient (63.7% versus 58.2%) survival rates were marginally higher for HCC–non-HCV patients than for HCC-HCV patients. In patients without HCC, pre-MELD and MELD era graft/patient survival rates for non-HCV patients were higher than those for HCV patients. The differences in survival rates for HCC patients with and without HCV were lower than those for non-HCC patients stratified by their HCV status. HCV had no additional negative impact on the post-LT survival of patients with HCC, and this was further confirmed by multivariate analysis. In conclusion, the survival of HCC patients has remained unchanged in the past 2 decades. HCV patients have a lower survival rate than non-HCV patients, regardless of their HCC status, but HCV has no additional negative impact on survival in patients with HCC. Liver Transpl 15:754–762, 2009. © 2009 AASLD.
Hepatosplenic γδ T-Cell Lymphoma After Liver Transplantation: Report of the First 2 Cases and Review of the Literature
Authors: Roelandt Philip R. , Maertens Johan , Vandenberghe Peter , Verslype Chris , Roskams Tania , Aerts Raymond , Nevens Frederik , Dierickx Daan
Published: June 2009

Abstract

Hepatosplenic γδ T-cell lymphoma is a rare lymphoproliferative disorder originating from natural killer–like Vδ1-lymphocytes. This subtype has been described after different types of solid organ transplants. In this article, we describe the first 2 cases after liver transplantation. Both patients had thrombocytopenia with (hepato)splenomegaly but without peripheral lymphadenopathies and sinusoidal infiltration of the liver and spleen by monomorphic γδ-lymphocytes on pathological examination. The clinical and pathological findings, immunophenotypical profile, prognosis, and treatment are highlighted. In order to make an early diagnosis, physicians who take care of liver transplant recipients should be aware of the characteristic features of this posttransplant lymphoproliferative disorder. Therefore, a diagnostic algorithm is proposed. Liver Transpl 15:686–692, 2009. © 2009 AASLD.
Amiodarone Pretreatment of Organ Donors Exerts Anti-Oxidative Protection But Induces Excretory Dysfunction in Liver Preservation and Reperfusion
Authors: Moussavian Mohammed Reza , Kollmar Otto , Schmidt Michael , Scheuer Claudia , Wagner Matthias , Slotta Jan Erik , Gronow Gernot , Justinger Christoph , Menger Michael Dieter , Schilling Martin Karl
Published: June 2009

Abstract

The continuous shortage of organs necessitates the use of marginal organs from donors with various diseases, including arrhythmia-associated cardiac failure. One of the most frequently used anti-arrhythmic drugs is amiodarone (AM), which is given in particular in emergency situations. Apart from its anti-arrhythmic actions, AM provides anti-oxidative properties in cardiomyocytes. Thus, we were interested in whether AM donor pretreatment affects the organ quality and function of livers procured for preservation and transplantation. Donor rats were pretreated with AM (5 mg/kg of body weight) 10 minutes before flush-out of the liver with a cold (4°C) histidine-tryptophan-ketoglutarate solution (n = 8). Livers were then stored for 24 hours at 4°C before ex situ reperfusion with a 37°C Krebs-Henseleit solution for 60 minutes in a nonrecirculating system. At the end of reperfusion, tissue samples were taken for histology and Western blot analysis. Animals with vehicle only (0.9% NaCl) served as ischemia/reperfusion controls (n = 8). Additionally, livers of untreated animals (n = 8) not subjected to 24 hours of cold ischemia served as sham controls. AM pretreatment effectively attenuated lipid peroxidation, stress protein expression, and apoptotic cell death. This was indicated by an AM-mediated reduction of malondialdehyde, heme oxygenase-1, and caspase-3 activation. However, AM treatment also induced mitochondrial damage and hepatocellular excretory dysfunction, as indicated by a significantly increased glutamate dehydrogenase concentration in the effluate and decreased bile production. In conclusion, AM donor pretreatment exerts anti-oxidative actions in liver preservation and reperfusion. However, these protective AM actions are counteracted by an induction of mitochondrial damage and hepatocellular dysfunction. Accordingly, AM pretreatment of donors for anti-arrhythmic therapy should be performed with caution. Liver Transpl 15:763–775, 2009. © 2009 AASLD.
A Randomized Pilot Trial of Oral Branched-Chain Amino Acids in Early Cirrhosis: Validation Using Prognostic Markers for Pre–Liver Transplant Status
Authors: Kawamura Etsushi , Habu Daiki , Morikawa Hiroyasu , Enomoto Masaru , Kawabe Joji , Tamori Akihiro , Sakaguchi Hiroki , Saeki Shigeru , Kawada Norifumi , Shiomi Susumu
Published: June 2009

Abstract

Because of the chronic shortage of liver donors, hepatologists are required to prolong the liver transplant waiting period by preserving the hepatic reserve of scheduled recipients. This study examined the effectiveness of oral branched-chain amino acids (BCAAs), using outcome markers indicating pretransplant hepatic reserve. Fifty-six consecutive eligible patients with Child class A cirrhosis without major complications were randomly assigned to receive oral BCAA granules (12.45 g/day) for least 1 year or no BCAAs. Differences between groups in the Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, asialoscintigraphic clearance index (CI), and complications were examined. Of 50 remaining patients, 27 received BCAAs, and 23 received no BCAAs (mean duration, 3.2 years). The mean annual changes in the MELD score, CTP score, and asialoscintigraphic CI were smaller in the BCAA group than in the control group (−0.06 ± 0.23 versus 0.10 ± 0.40, P = 0.024, 0.06 ± 0.30 versus 0.30 ± 0.48, P = 0.037, and 0.00 ± 0.02 versus 0.02 ± 0.04, P = 0.040, respectively). The mean annual changes in the serum total bilirubin and the serum albumin in the BCAA group were better preserved than those in the control group (−0.07 ± 0.20 versus 0.12 ± 0.18 mg/dL, P < 0.001, and 0.07 ± 0.13 versus −0.02 ± 0.19 g/dL, P = 0.005, respectively); other laboratory variables were not significant. The incidence of overall major cirrhotic complications was lower in the BCAA group than in the control group [14.8% (4 of 27 patients) versus 30.4% (7 of 23 patients) at 3 years, P = 0.043]; only ascites was significant individually. In conclusion, early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis. Liver Transpl 15:790–797, 2009. © 2009 AASLD.
Predictors of Sustained Virological Response After Antiviral Treatment for Hepatitis C Recurrence Following Liver Transplantation
Authors: Cescon Matteo , Grazi Gian Luca , Cucchetti Alessandro , Vetrone Gaetano , Ravaioli Matteo , Ercolani Giorgio , Morelli Maria Cristina , Piscaglia Fabio , Tamè Mariarosa , Pinna Antonio Daniele
Published: June 2009

Abstract

Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety-nine HCV-positive/hepatitis B surface antigen–negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty-five patients (25%) achieved an SVR. Twenty-seven donor-related, recipient-related, HCV-related, and immunosuppression-related variables were investigated for their association with SVR. In logistic regression analysis, donor age < 60 years (odds ratio = 4.45, 95% confidence interval = 1.39-14.19, P = 0.01), viral genotype other than 1 (odds ratio = 4.97, 95% confidence interval = 1.59-15.48, P = 0.006), and the use of CyA during treatment (odds ratio = 6.85, 95% confidence interval = 2.15-21.73, P = 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P = 0.02 and P = 0.005, respectively) and a greater use of anti-CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P = 0.03, P < 0.001, and P = 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P = 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT. Liver Transpl 15:782–789, 2009. © 2009 AASLD.
Unexplained and Prolonged Perioperative Hypotension After Orthotopic Liver Transplantation: Undiagnosed Systemic Mastocytosis
Authors: Willingham Darrin L. , Peiris Prith , Canabal Juan M. , Krishna Murli , Hewitt Winston R. , Shine Timothy S. J. , Arasi Lisa C. , Aranda-Michel Jaime , Hughes Christopher B. , Kramer David J.
Published: June 2009

Abstract

Arterial vasodilation is common in end-stage liver disease, and systemic hypotension often may develop, despite an increase in cardiac output. During the preparation for and the performance of orthotopic liver transplantation, expected and transient hypotension may be caused by induction agents, anesthetic agents, liver mobilization, or venous clamping. A mild decrease of the already low systemic vascular resistance is often observed, and intermittent use of short-acting agents for vasopressor support is not uncommon. In this report, we describe a patient with unexpected and prolonged hypotension due to vasodilation during and after orthotopic liver transplantation. The preoperative end-stage liver disease evaluation, intraoperative events, and intensive care unit course were reviewed, and no cause for the vasodilation and prolonged hypotension was evident. The explant pathology report was later available and showed systemic mastocytosis. We hypothesize that the unexpected hypotension and vasodilation were caused by mast cell degranulation and its systemic effects on arterial tone. Liver Transpl 15:701–708, 2009. © 2009 AASLD.
Infliximab Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease After Orthotopic Liver Transplantation: A Case Report
Authors: Piton Gaël , Larosa Fabrice , Minello Anne , Becker Marie-Claude , Mantion Georges , Aubin François , Deconinck Eric , Hillon Patrick , Di Martino Vincent
Published: June 2009

Abstract

Acute graft-versus-host disease (GVHD) following orthotopic liver transplantation is a rare but severe disease with a 75% death rate in adults. Various therapeutic strategies have been proposed for steroid-refractory GVHD, but there is still no consensus. Tumor necrosis factor-alpha is a key inflammatory cytokine involved in acute GVHD physiopathology, and infliximab has shown encouraging results for the treatment of acute GVHD following hematopoietic stem cell transplantation. We report the first case of acute GVHD following liver transplantation that was refractory to steroids and anti-lymphocyte globulin but was successfully treated with infliximab. Liver Transpl 15:682–685, 2009. © 2009 AASLD.
Are current recommendations to diagnose orthostatic hypotension in Parkinson's disease satisfactory?
Authors: Jamnadas‐Khoda Jenny , Koshy Suma , Mathias Christopher J. , Muthane Uday B. , Ragothaman Mona , Dodaballapur Subbakrishna K.
Published: June 2009

We interviewed 50 Parkinson's disease (PD) patients using a questionnaire to verify the reliability of orthostatic symptoms in warning the presence of orthostatic hypotension (OH). OH is defined as 20 mm Hg systolic or 10 mm Hg diastolic BP fall within 3 min of tilting or standing but if this fall occurs after 3 min we called it ‘late OH’ (L‐OH). We compared if OH in Parkinson's disease (PD) was more frequent after head‐up tilt or on standing and if the period of postural challenge matters in detecting OH. Twenty‐one (42%) patients had OH that occurred twice more often after tilting (n = 20) than on standing (n = 10). OH occurred within 3 min of tilting in 9 patients (18%) and appeared beyond the currently recommended 3 min in 11 patients (55%) (L‐OH). Ten of the 20 patients developing OH on tilting were symptomatic. The 10 patients who had OH on standing were asymptomatic. Reporting of symptoms was independent of age or severity of BP fall. Most (90%) patients reporting orthostatic symptoms on standing had OH on tilting for 3 min. Orthostatic symptoms in PD have a high specificity but low sensitivity in predicting OH. In Parkinson's disease OH occurs often after tilting than on standing and is delayed (after 3 min). As OH in PD is often asymptomatic and delayed it could contribute to falls and increase morbidity. We suggest routine evaluation of OH in PD by tilting them longer than the recommended 3 minutes to detect delayed OH. © 2009 Movement Disorder Society
Paraneoplastic movement disorders
Authors: Grant Robin , Graus Francesc
Published: June 2009

Paraneoplastic movement disorders are rare autoimmune nonmetastatic complications of cancer. Common paraneoplastic movement disorders include cerebellar syndrome, opsoclonus myoclonus, basal ganglia disorders, stiff person syndrome, and neuromyotonia. Syndromes usually present before cancer diagnosis and are commonly associated with one or more serum antibodies. Increasing numbers of antibodies have been identified (Hu, Yo, Ri, CV2, amphiphysin, Ma, Ta, Tr, NMDA, mGluR1, PCA2, ANNA‐3, VGCCA). Antibodies are highly correlated with the likelihood of an underlying cancer and are closely associated with certain tumors. Clinical clues to paraneoplastic aetiology include speed of onset, severity, speed of progression, resistance to treatment, and more widespread neurological signs than one would expect from nonparaneoplastic aetiologies. Cancer should be sought in those with classical presentations and those with possible presentations who have paraneoplastic antibodies. If no tumor is found on initial investigation, interval screening is advisable. The most common associated cancers found are small cell lung cancer, breast, gynaecological, testicular, lymphoma, and thymoma. Early identification and treatment sometimes leads to neurological improvement and may improve cancer prognosis. Prognosis is dependent on the tumor type and its likely response to treatment. © 2009 Movement Disorder Society
Association of DRD3 and GRIN2B with impulse control and related behaviors in Parkinson's disease
Authors: Lee Jee‐Young , Lee Eun Kyung , Park Sung Sup , Lim Ji‐Yeon , Kim Hee Jin , Kim Ji Sun , Jeon Beom S
Published: June 2009

We aimed to assess whether allelic variants of dopamine receptor, glutamate receptor, and serotonin transporter genes are associated with the appearance of impulse control and related behaviors (ICRB) in Parkinson's disease (PD) with dopamine replacement therapy (DRT). We surveyed ICRB in consecutive Korean patients with PD who were treated with stable DRT using modified Minnesota Impulsive Disorders Interview over a period of 4 months. In the 404 patients who completed the interview and the 559 Korean healthy normal controls, genotyping was performed for variants of the DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.366C>G, c.2664C>T and c.‐200T>G, and the promoter region of the serotonin transporter gene (5‐HTTLPR). Behavioral abnormalities suggestive of ICRB including compulsive buying, gambling, sexual behavior and eating, and punding, were present in 14.4% of the patients. Variants of DRD2 and 5‐HTTLPR were not associated with the risk of developing ICRB. However, the AA genotype of DRD3 p.S9G and the CC genotype of GRIN2B c.366C>G were more frequent in patients with ICRB than in nonaffected patients (odds ratio [OR] = 2.21, P = 0.0094; and 2.14, P = 0.0087, after adjusting for age and sex). After controlling for clinical variables in the multivariate analysis, carriage of either AA genotype of DRD3 or CC genotype of GRIN2B was identified as an independent risk factor for ICRB (adjusted OR: 2.57, P = 0.0087). Variants of DRD3 p.S9G and GRIN2B c.366C>G may be associated with the appearance of ICRB in PD. © 2009 Movement Disorder Society
Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS
Authors: Schmahmann Jeremy D. , Gardner Raquel , MacMore Jason , Vangel Mark G.
Published: June 2009

To develop a brief ataxia rating scale (BARS) for use by movement disorder specialists and general neurologists. Current ataxia rating scales are cumbersome and not designed for clinical practice. We first modified the International Cooperative Ataxia Rating Scale (ICARS) by adding seven ataxia tests (modified ICARS, or MICARS), and observed only minimally increased scores. We then used the statistics package R to find a five‐test subset in MICARS that would correlate best with the total MICARS score. This was accomplished first without constraints and then with the clinical constraint requiring one test each of Gait, Kinetic Function‐Arm, Kinetic Function‐Leg, Speech, and Eye Movements. We validated these clinical constraints by factor analysis. We then validated the results in a second cohort of patients; evaluated inter‐rater reliability in a third cohort; and used the same data set to compare BARS with the Scale for the Assessment and Rating of Ataxia (SARA). Correlation of ICARS with the seven additional tests that when added to ICARS form MICARS was 0.88. There were 31,481 five‐test subtests (48% of possible combinations) that had a correlation with total MICARS score of ≥0.90. The strongest correlation of an unconstrained five‐test subset was 0.963. The clinically constrained subtest validated by factor analysis, BARS, had a correlation with MICARS‐minus‐BARS of 0.952. Cronbach alpha for BARS and SARA was 0.90 and 0.92 respectively; and inter‐rater reliability (intraclass correlation coefficient) was 0.91 and 0.93 respectively. BARS is valid, reliable, and sufficiently fast and accurate for clinical purposes. © 2009 Movement Disorder Society
Asymptotic approximation of eigenelements of the Dirichlet problem for the Laplacian in a domain with shoots
Authors: Amirat Youcef , Chechkin Gregory A. , Gadyl'shin Rustem R.
Published: June 2009

We study the asymptotic behavior of the eigenelements of the Dirichlet problem for the Laplacian in a two‐dimensional bounded domain with thin shoots, depending on a small parameter ε. Under the assumption that the width of the shoots goes to zero, as ε tends to zero, we construct the limit (homogenized) problem and prove the convergence of the eigenvalues and eigenfunctions to the eigenvalues and eigenfunctions of the limit problem, respectively. Under the additional assumption that the shoots, in a fixed vicinity of the basis, are straight and periodic, and their width and the distance between the neighboring shoots are of order ε, we construct the two‐term asymptotics of the eigenvalues of the problem, as ε→0. Copyright © 2009 John Wiley & Sons, Ltd.
Non‐invasive determination of tissue thermal parameters from high intensity focused ultrasound treatment monitored by volumetric MRI thermometry
Authors: Dragonu Iulius , de Oliveira Philippe Lourenço , Laurent Christophe , Mougenot Charles , Grenier Nicolas , Moonen Chrit T. W. , Quesson Bruno
Published: June 2009

A method is proposed for estimating the perfusion rate, thermal diffusivity, and the absorption coefficient that influence the local temperature during high intensity focused ultrasound (HIFU) thermotherapy procedures. For this purpose, HIFU heating experiments (N = 100) were performed ex vivo on perfused porcine kidney (N = 5) under different flow conditions. The resulting spatio‐temporal temperature variations were measured non‐invasively by rapid volumetric MR‐temperature imaging. The bio‐heat transfer (BHT) model was adapted to describe the spatio‐temporal evolution of tissue temperature in the cortex. Absorption and perfusion coefficients were determined by fitting the integrated thermal load (spatial integration of the thermal maps) curves in time with an analytical solution of the BHT equation proposed for single point HIFU heating. Thermal diffusivity was determined independently by analyzing the spatial spread of the temperature in time during the cooling period. Absorption coefficient and thermal diffusivity were found to be independent of flow, with mean and average values of 11.0 ± 1.85 mm3 · K · J−1 and 0.172 ± 0.003 mm2 · s−1, respectively. A linear dependence of the calculated perfusion rate with flow was observed with a slope of 9.20 ± 0.75 mm−3. The perfusion was found to act as a scaling term with respect to temperature but with no effect on the spatial spread of temperature which only depends on the thermal diffusivity. All results were in excellent agreement with the BHT model, indicating that this model is suitable to predict the evolution of temperature in perfused organs. This quantitative approach allows for determination of tissue thermal parameters with excellent precision (within 10%) and may thus help in quantifying the influence of perfusion during MR guided high intensity focused ultrasound (MRgHIFU). Copyright © 2009 John Wiley & Sons, Ltd.
A new analytical method for system of ODEs
Authors: Aminikhah Hossein , Biazar Jafar
Published: June 2009

In this article, a new homotopy perturbation method (NHPM) is introduced to obtain exact solutions of system of ODEs. Theoretical considerations are discussed. Comparison of the results of applying NHPM with those of homotopy perturbation method (HPM) and Adomia's decomposition method (ADM) leads to significant consequences. Three examples, including stiff system of linear and nonlinear ODEs are given to demonstrate the efficiency of the new method. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2010
Synthesis of thermo‐responsive microgels in supercritical carbon dioxide using ethylene glycol dimethacrylate as a cross‐linker
Authors: Hu Yaodong , Cao Liqin , Xiao Feng , Wang Jide
Published: June 2009

Herein, we report the preparation of thermo‐responsive polymers in a green medium. The white, dry, fine powders were obtained directly from the cross‐linking polymerization of N‐isopropylacrylamide (NIPA) in supercritical carbon dioxide (scCO2) at pressures ranging from 10 to 28 MPa utilizing ethylene glycol dimethacrylate (EGDMA) as a cross‐linker. The effects of reaction pressure, cross‐linker ratio, initiator concentration, and reaction time were investigated. In the presence of this cross‐linker (26.4% w/w), much smaller poly(N‐isopropylacrylamide) (PNIPA) microgels (<0.2 µm diameter) were formed, and it was shown that the particle size and the morphology of the polymer were strongly dependent on the cross‐linker ratio in scCO2. Copyright © 2009 John Wiley & Sons, Ltd.
Micro fabrication of microlens arrays by micro dispensing
Authors: Cheng Hsin‐Chung , Wang Chau‐Hsiang , Huang Chiung‐Fang , Shen Yung‐Kang , Lin Yi , Sheu Dong‐Yea , Hu Yi‐Han
Published: June 2009

In this study, master of the microlens arrays is fabricated using micro dispensing technology, and then electroforming technology is employed to replicate the Ni mold insert of the microlens arrays. Finally, micro hot embossing is performed to replicate the molded microlens arrays from the Ni mold insert. The resin material is used as the dispensing material, which is dropped on a glass substrate. The resin is exposed to a 380 W halogen light. It becomes convex under surface tension on the glass substrate. A master for the microlens arrays is then obtained. A 150‐nm‐thick copper layer is sputtered on the master as an electrically conducting layer. The electroforming method replicates the Ni mold insert from the master of the microlens arrays. Finally, micro hot embossing is adopted to replicate the molded microlens arrays. The micro hot embossing experiment employs optical films of polymethylmethacrylate (PMMA) and polycarbonate (PC). The processing parameters of micro hot embossing are processing temperature, embossing pressure, embossing time, and de‐molding temperature. Taguchi's method is applied to optimize the processing parameters of micro hot embossing for molded microlens arrays. An optical microscope and a surface profiler are utilized to measure the surface profile of the master, the Ni mold insert and the molded microlens arrays. AFM is employed to measure the surface roughness of the master, the Ni mold insert and the molded microlens arrays. The sag height and focal length are determined to elucidate the optical characteristics of the molded microlens arrays. Copyright © 2009 John & Sons, Ltd.
Effect of electron beam irradiation on mechanical and thermal properties of waste polyamide copolymer blended with nitrile‐butadiene rubber
Authors: El‐Nemr Khaled F. , Hassan Medhat M. , Ali Magdy A.
Published: June 2009

In the present study, the effect of electron beam irradiation on the morphological, thermal, and mechanical properties of waste polyamide copolymer (WPA‐66/6) blended with different contents of acrylonitrile butadiene rubber (NBR) were studied. The prepared blends were subjected to irradiation doses up to 150 kGy and the structural modifications were discussed; non‐irradiated blends were used as control. Mechanical properties, namely, tensile strength (TS), yield strength, elongation at break, and hardness, were followed up as functions of irradiation dose and degree of loading with rubber content. On the other hand, the influence of irradiation dose on the thermal parameters, melting temperature, heat of fusion, ΔHm of the recycled PA copolymer, and its blend with NBR were also investigated. Copyright © 2009 John Wiley & Sons, Ltd.
Arg‐85 and Thr‐430 in murine 5‐aminolevulinate synthase coordinate acyl‐CoA‐binding and contribute to substrate specificity
Authors: Lendrihas Thomas , Zhang Junshun , Hunter Gregory A. , Ferreira Gloria C.
Published: June 2009

5‐Aminolevulinate synthase (ALAS) controls the rate‐limiting step of heme biosynthesis in mammals by catalyzing the condensation of succinyl‐coenzyme A and glycine to produce 5‐aminolevulinate, coenzyme‐A (CoA), and carbon dioxide. ALAS is a member of the α‐oxoamine synthase family of pyridoxal 5′‐phosphate (PLP)‐dependent enzymes and shares high degree of structural similarity and reaction mechanism with the other members of the family. The X‐ray crystal structure of ALAS from Rhodobacter capsulatus reveals that the alkanoate component of succinyl‐CoA is coordinated by a conserved arginine and a threonine. The functions of the corresponding acyl‐CoA‐binding residues in murine erthyroid ALAS (R85 and T430) in relation to acyl‐CoA binding and substrate discrimination were examined using site‐directed mutagenesis and a series of CoA‐derivatives. The catalytic efficiency of the R85L variant with octanoyl‐CoA was 66‐fold higher than that of the wild‐type protein, supporting the proposal of this residue as key in discriminating substrate binding. Substitution of the acyl‐CoA‐binding residues with hydrophobic amino acids caused a ligand‐induced negative dichroic band at 420 nm in the CD spectra, suggesting that these residues affect substrate‐mediated changes to the PLP microenvironment. Transient kinetic analyses of the R85K variant‐catalyzed reactions confirm that this substitution decreases microscopic rates associated with formation and decay of a key reaction intermediate and show that the nature of the acyl‐CoA tail seriously affect product binding. These results show that the bifurcate interaction of the carboxylate moiety of succinyl‐CoA with R85 and T430 is an important determinant in ALAS function and may play a role in substrate specificity.
Modeling the effects of obesity and weight gain on PSA velocity
Authors: Rundle Andrew G. , Neugut Alfred I.
Published: June 2009

BACKGROUND

Hemodilution theory states that higher blood volume in obese men effectively dilutes circulating PSA levels resulting in lower PSA test results. Here we apply hemodilution theory to model the effect of weight gain on PSA velocity.

METHODS

Hemodilution formulas were used to model PSA velocity for a series of plausible scenarios in which initial weight and weight gain were varied. The formulas were also applied to published summary data on weight, weight change and PSA velocity from the Prostate Cancer Prevention Trial (PCPT).

RESULTS

Under hemodilution theory, PSA velocity is understood to be influenced by total circulating PSA mass (ng of PSA) and BMI at the initial test and total circulating PSA mass and BMI at the subsequent test. PSA velocity in a man with a stable BMI of 35 is estimated to be 13% lower than in a man with a stable BMI of 25. A gain of 4 BMI units is predicted to attenuate PSA velocity by as much as 25%. When applied to summary data from the PCPT, the formulas estimate that a 10 pound weight gain causes a −0.028 ng/ml change in PSA, which closely matches PCPT results where a 10 pound weight gain caused a −0.024 ng/ml change in PSA. We provide software to implement the hemodilution formulas to model PSA velocity for different weights and changes in weight through time (http://www.eheintl.com/psa.jsp).

CONCLUSION

Stable obesity and weight gain both independently attenuate PSA velocity, potentially obscuring clinically relevant changes in circulating PSA. Prostate 69: 1573–1578, 2009. © 2009 Wiley‐Liss, Inc.
Inhibition of Aβ42 aggregation using peptides selected from combinatorial libraries
Authors: Baine Michael , Georgie Daniel S. , Shiferraw Elelta Z. , Nguyen Theresa P. T. , Nogaj Luiza A. , Moffet David A.
Published: June 2009

Increasing evidence suggests that the aggregation of the small peptide Aβ42 plays an important role in the development of Alzheimer's disease. Inhibiting the initial aggregation of Aβ42 may be an effective treatment for preventing, or slowing, the onset of the disease. Using an in vivo screen based on the enzyme EGFP, we have searched through two combinatorially diverse peptide libraries to identify peptides capable of inhibiting Aβ42 aggregation. From this initial screen, three candidate peptides were selected and characterized. ThT studies indicated that the selected peptides were capable of inhibiting amyloid aggregation. Additional ThT studies showed that one of the selected peptides was capable of disaggregating preformed Aβ42 fibers. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
On analysing warranty data from repairable items
Authors: Marshall Sarah E. , Chukova Stefanka
Published: June 2009

Fitting models to failure data is an important topic in reliability. The resulting models can be useful both for manufacturers as well as for end‐users. In this paper we provide details of some methods from the literature which can be used as a starting point when analysing and fitting models to failure data from repairable items. In particular we focus on obtaining analytical estimates of the intensity of a non‐homogeneous Poisson process. We illustrate some of these methods on failure data from the warranty database of a major car manufacturer. Copyright © 2009 John Wiley & Sons, Ltd.
A control chart based on likelihood ratio test for monitoring process mean and variability
Authors: Zhang Jiujun , Zou Changliang , Wang Zhaojun
Published: June 2009

Recently, monitoring the process mean and variance simultaneously by using a single chart has drawn more and more attention. In this paper, we propose a new single chart that integrates the EWMA procedure with the generalized likelihood ratio (GLR) test statistics for jointly monitoring both the process mean and variance. It can be easily designed and constructed, and its average run length can be evaluated by a two‐dimensional Markov chain model. Owing to the good properties of the GLR test and EMWA, computation results show that it provides quite a robust and satisfactory performance in various cases, including the detection of the decrease in variability and the individual observation at the sampling point, which are very important in many practical applications but may not be well handled by the existing approaches in the literature. The application of our proposed method is illustrated by a real data example from chemical process control. Copyright © 2009 John Wiley & Sons, Ltd.
Regulation of dynamin 2 and G protein‐coupled receptor kinase 2 in rat nucleus accumbens during acute and repeated cocaine administration
Authors: Schroeder Joseph A. , Mccafferty Mary R. , Unterwald Ellen M.
Published: June 2009

Exposure to cocaine causes many neuroadaptations including alterations in several neurotransmitter receptors and transporters. This study investigated potential mechanisms of cocaine‐induced receptor and transporter regulation by measuring levels of two proteins involved in receptor and transporter trafficking, dynamin 2 and G protein‐coupled receptor kinase 2 (GRK2). Male Fischer rats received three daily injections of cocaine, 15 mg/kg, in a binge‐pattern (at 1 h intervals) for 1, 3, or 14 days. Brain regions of interest were collected 30 min after the last injection and proteins measured by Western blot. Acute binge‐pattern cocaine administration produced a significant increase in both dynamin 2‐ and GRK2‐immunoreactivity (227% and 358% of control) in the nucleus accumbens and GKR2 (150% of control) in the caudate putamen. Tolerance to this effect occurred, as levels of both proteins returned to baseline after 3 days of cocaine. In contrast, dynamin 2 and GRK2 were significantly decreased in the nucleus accumbens after chronic cocaine. This pattern of regulation was unique to the nucleus accumbens and not seen in the frontal cortex or substantia nigra. Pretreatment with either the dopamine (DA) D1 receptor antagonist SCH 23390 or D2 receptor antagonist eticlopride prior to acute cocaine blocked the upregulation of dynamin 2 and GRK2 in the nucleus accumbens. However, only eticlopride was effective in attenuating the decrease in these proteins following chronic cocaine exposure. These results demonstrate that two proteins involved in receptor and transporter trafficking are selectively regulated in the nucleus accumbens following acute versus chronic cocaine exposure, and dopamine receptor activation is required for this regulation. Synapse 63:863–870, 2009. © 2009 Wiley‐Liss, Inc.
In vitro autoradiography and in vivo evaluation in cynomolgus monkey of [18F]FE‐PE2I, a new dopamine transporter PET radioligand
Authors: Varrone Andrea , Steiger Carsten , Schou Magnus , Takano Akihiro , Finnema Sjoerd J. , Guilloteau Denis , Gulyás Balázs , Halldin Christer
Published: June 2009

This study evaluated the in vitro and in vivo characteristics of a new dopamine transporter (DAT) radioligand, [18F]fluoroethyl(FE)PE2I, by autoradiography from postmortem human brain and by positron emission tomography (PET) in three cynomolgus monkeys. In the autoradiography experiments, high [18F]FE‐PE2I accumulation was observed in caudate and putamen that was selectively abolished by GBR12909 or β‐CIT but not by maprotiline. High doses of citalopram (>5 μM) also inhibited [18F]FE‐PE2I binding in the striatum. In vitro Ki of the radioligand was 12 nM at rodent dopamine transporter. [18F]FE‐PE2I brain uptake measured by PET was ∼4–5% of the injected dose, with highest uptake in striatum followed by midbrain and thalamus, lower uptake in neocortex, and lowest in cerebellum. Peak specific binding in striatum was reached ∼40 min and in midbrain 20–30 min postinjection. The ratio‐to‐cerebellum was 7–10 in striatum and 1.5–2.3 in midbrain. BPND measured with simplified reference tissue method using the cerebellum as reference region was 4.5 in striatum and 0.6 in midbrain. No displacement was shown after citalopram or maprotiline administration, while GBR12909 decreased the binding in striatum and midbrain to the level of cerebellum. [18F]FE‐PE2I showed relatively fast elimination and metabolism with the presence of two metabolite peaks with similar retention time as the labeled metabolites of [11C]PE2I. [18F]FE‐PE2I showed in vivo selectivity for the DAT and compared with [11C]PE2I, it showed faster kinetics and earlier peak equilibrium. The potential influence of the two radiometabolites on PET quantification requires further evaluation. Synapse 63:871–880, 2009. © 2009 Wiley‐Liss, Inc.
Cytogenotoxicity induced by PBDE‐47 combined with PCB153 treatment in SH‐SY5Y cells
Authors: He Weihong , Wang Aiguo , Xia Tao , Gao Ping , Xu Bayi , Xu Zhixia , He Ping , Chen Xuemin
Published: June 2009

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are important recalcitrant halogenated compounds that have been regarded as major environmental pollutants. Recently, their concurrent appearance in the environment and humans and their structural and toxicological profile similarities have sparked interest in the potential toxicologic consequences of their coexposure. The aim of the current study was to evaluate the cytogenotoxic effects induced by 2,2′,4,4′‐tetrabromodiphenyl ether (PBDE‐47) combined with 2,2′,4,4′,5,5′‐hexachlorobiphenyl (PCB153) treatment in human neuroblastoma cells (SH‐SY5Y) in vitro. SH‐SY5Y cells were exposed to different concentrations of PBDE‐47 (0, 2, 4, 8 μM) with or without PCB153 (5 μM) for 24 h. Thereafter, the cell viability, DNA damage, chromosomal abnormalities, and DNA‐protein crosslinks (DPC) were determined. The results show that PBDE‐47 and PCB153 alone and in combination induce DNA damage, with an increase in the frequency of micronuclei (MN) and DPC formation with increasing PBDE‐47 concentration. In cells coexposed to PBDE‐47 and PCB153, the cell viability significantly decreased while the MN frequency, DNA damage and DPC formation were all obviously increased compared to those of cells treated with the corresponding concentrations of PBDE‐47 or PCB153 alone. Factorial analysis suggests that there were interactions between PBDE‐47 and PCB153. The results imply that PBDE‐47 interacts with PCB153 to inhibit cell viability and induce DNA damage, DPC formation, and chromosome abnormalities. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 564–572, 2010.