bluuebunny/crossref_metadata_2025 huggingface dataset:
BAC array CGH distinguishes mutually exclusive alterations that define clinicogenetic subtypes of gliomas
Authors: Idbaih Ahmed , Marie Yannick , Lucchesi Carlo , Pierron Gaëlle , Manié Elodie , Raynal Virginie , Mosseri Véronique , Hoang‐Xuan Khê , Kujas Michèle , Brito Isabel , Mokhtari Karima , Sanson Marc , Barillot Emmanuel , Aurias Alain , Delattre Jean‐Yves , Delattre Olivier
Published: December 2007

The pathological classification of gliomas constitutes a critical step of the clinical management of patients, yet it is frequently challenging. To assess the relationship between genetic abnormalities and clinicopathological characteristics, we have performed a genetic and clinical analysis of a series of gliomas. A total of 112 gliomas were analyzed by comparative genomic hybridization on a BAC array with a 1 megabase resolution. Altered regions were identified and correlation analysis enabled to retrieve significant associations and exclusions. Whole chromosomes (chrs) 1p and 19q losses with centromeric breakpoints and EGFR high level amplification were found to be mutually exclusive, permitting identification of 3 distinct, nonoverlapping groups of tumors with striking clinicopathological differences. Type A tumors with chrs 1p and 19q codeletion exhibited an oligodendroglial phenotype and a longer patient survival. Type B tumors were characterized by EGFR amplification. They harbored a WHO high grade of malignancy and a short patient survival. Finally, type C tumors displayed none of the previous patterns but the presence of chr 7 gain, chr 9p deletion and/or chr 10 loss. It included astrocytic tumors in patients younger than in type B and whose prognosis was highly dependent upon the number of alterations. A multivariate analysis based on a Cox model shows that age, WHO grade and genomic type provide complementary prognostic informations. Finally, our results highlight the potential of a whole‐genome analysis as an additional diagnostic in cases of unclear conventional genetic findings. © 2007 Wiley‐Liss, Inc.
Temporal trends in the incidence rate of childhood cancer in Germany 1987–2004
Authors: Spix Claudia , Eletr Dina , Blettner Maria , Kaatsch Peter
Published: December 2007

The German Childhood Cancer Registry regularly presents graphs of childhood cancer incidence rates by period, but no systematic analysis. The Automated Childhood Cancer Information System‐project found an increasing trend in Europe. Against this background we present the first detailed trend analysis of childhood (aged under 15) malignancies in Germany. We examined incidence rates separately in western Germany 1987–2004 and eastern Germany 1991–2004. We analyzed all malignancies, all main diagnostic groups and relevant subsets using an age‐period‐cohort model. Additionally we fitted fractional polynomials to assess the linearity of the drift. All malignancies combined (excluding Central Nervous System‐tumors and neuroblastoma) show a significant trend: +0.7% in western and +1.1% per year in eastern Germany. The overall trend in Germany is mostly due to the significant increase in lymphoid leukemia, which increased significantly in western Germany (+0.7% per year) and significantly nonlinearly in eastern Germany (+3.3% per year until 1998, +0.8% since 1998), catching up from a level 20% below western Germany. This could be due to life style changes since the reunification in eastern Germany influencing early immune system training. We found no trends for acute non‐lymphocytic leukemia and non‐Hodgkin lymphoma. Hodgkin's disease shows a cohort effect in western Germany after reunification. Improved registration of CNS tumors led to an increase. Neuroblastoma yielded a period effect in western Germany due to screening. With the exception of germ cell tumors, further observations for solid tumor entities are in agreement with those reported for Europe. © 2007 Wiley‐Liss, Inc.
Birth‐related characteristics, congenital malformation, maternal reproductive history and neuroblastoma: The ESCALE study (SFCE)
Authors: Munzer Caroline , Menegaux Florence , Lacour Brigitte , Valteau‐Couanet Dominique , Michon Jean , Coze Carole , Bergeron Christophe , Auvrignon Anne , Bernard Frédéric , Thomas Caroline , Vannier Jean‐Pierre , Kanold Justyna , Rubie Hervé , Hémon Denis , Clavel Jacqueline
Published: December 2007

Since neuroblastoma occurs very early in children's lives, it has been hypothesized that pre‐ and perinatal factors may play a role in its etiology. This study investigated the role of birth characteristics, congenital malformation and maternal reproductive history in neuroblastoma. The data used were generated by the national population‐based case–control study, ESCALE, conducted in France in 2003–2004. The mothers of 191 neuroblastoma cases and 1,681 controls, frequency‐matched by age and gender, were interviewed by telephone, using a standardized questionnaire, on several factors including pregnancy, medical history, lifestyle, childhood medical conditions and exposures. A positive association between congenital malformation and all neuroblastoma cases was observed [Odds ratio (OR) = 2.2, 95% confidence interval (95% CI): 1.1–4.5]. Congenital malformations were highly associated to neuroblastoma in children aged less than 1 year (OR = 16.8, 95% CI: 3.1–90), while no association was observed in children aged 1 year or more (OR = 1.0, 95% CI: 0.3–2.9). A negative association with a maternal history of spontaneous abortions was also found (OR = 0.6, 95% CI: 0.4–0.9). The results strongly support the hypothesis that congenital anomalies may be associated with neuroblastoma, particularly in infant (less than 1 year of age). © 2007 Wiley‐Liss, Inc.
Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti‐inflammatory drug‐activated gene
Authors: Kim Jeong Hong , Chang Jung Hyun , Rhee Kwang‐Hyeon , Yoon Joo‐Heon , Kwon Soon Ho , Song Keejae , Lee Kun Wayn , Cho Chang Il , Jeon Ju Hyun , Kim Kyung‐Su
Published: December 2007

Nonsteroidal anti‐inflammatory drug‐activated gene‐1 (NAG‐1) has recently been shown to be induced by nonsteroidal anti‐inflammatory drugs (NSAIDs) and to have proapoptotic and antitumorigenic activities. Although sulindac sulfide induced apoptosis in sinonasal cancer cells, the relationship between NAG‐1 and NSAIDs has not been determined. In this study, we investigated the induction of apoptosis in sinonasal cancer cells treated by various NSAIDs and the role of NAG‐1 expression in this induction. The effect of NSAIDs on normal human nasal epithelial (NHNE) cells was also examined to evaluate their safety on normal cells. Finally, thein vivoanti‐tumorigenic activity of NSAIDs in mice was investigated. In AMC‐HN5 human sinonasal carcinoma cells, indomethacin was the most potent NAG‐1 inducer and caused NAG‐1 expression in a time‐ and dose‐dependent manner. The induction of NAG‐1 expression preceded the induction of apoptosis. Conditioned medium from NAG‐1‐overexpressingDrosophilacells inhibited proliferation of sinonasal cancer cells and induced apoptosis. In addition, in NAG‐1 small interfering RNA‐transfected cells, apoptosis induced by indomethacin was suppressed. In contrast, NAG‐1 expression and apoptosis were not induced by NSAIDs or conditioned medium in NHNE cells. Furthermore, indomethacin induced a dose‐dependentin vivoincrease in the expression of NAG‐1 mRNA in the mice tumors and the volume of xenograft tumors of AMC‐HN5 cells in indomethacin‐treated nude mice was reduced compared to that in control mice. In conclusion, indomethacin exerts proapoptotic and antitumorigenic effects in sinonasal cancer cells through the induction of NAG‐1 and can be considered a safe and effective chemopreventive agent against sinonasal cancer. © 2007 Wiley‐Liss, Inc.
Serum lipid levels and the risk of biliary tract cancers and biliary stones: A population‐based study in China
Authors: Andreotti Gabriella , Chen Jinbo , Gao Yu‐Tang , Rashid Asif , Chang Shih‐Chen , Shen Ming‐Chang , Wang Bing‐Sheng , Han Tian‐Quan , Zhang Bai‐He , Danforth Kim N. , Althuis Michelle D. , Hsing Ann W.
Published: December 2007

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Gallstones, the predominant risk factor for biliary cancers, are linked with hyperlipidemia. As part of a population‐based case‐control study conducted in Shanghai, China, we examined the associations of serum lipid levels with biliary stones and cancers. We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile duct, and 55 ampulla of Vater), 981 biliary stone cases and 858 healthy individuals randomly selected from the population. Participants completed an in‐person interview and gave overnight fasting blood samples. Participants in the highest quintile of triglycerides (≥160 mg/dl) had a 1.4‐fold risk of biliary stones (95% CI = 1.1–1.9), a 1.9‐fold risk of gallbladder cancer (95% CI = 1.3–2.8), and a 4.8‐fold risk of bile duct cancer (95% CI = 2.8–8.1), compared to the reference group (third quintile: 90–124 mg/dl). Participants in the lowest quintile of high‐density lipoprotein (HDL) (<30 mg/dl) had a 4.2‐fold risk of biliary stones (95% CI = 3.0–6.0), an 11.6‐fold risk of gallbladder cancer (95% CI = 7.3–18.5), and a 16.8‐fold risk of bile duct cancer (95% CI = 9.1–30.9), relative to the reference group (third quintile: 40–49 mg/dl). In addition, total cholesterol, low‐density lipoprotein (LDL) and apolipoprotein A (apo A) were inversely associated with biliary stones; whereas low levels as well as high levels of total cholesterol, LDL, apo A and apolipoprotein B (apo B) were associated with excess risks of biliary tract cancers. Our findings support a role for serum lipids in gallstone development and biliary carcinogenesis. © 2007 Wiley‐Liss, Inc.
Colorectal cancer cells express functional cell surface‐bound TGFβ
Authors: Baker Kristi , Raut Pooja , Jass Jeremy R.
Published: December 2007

Disruptions to the TGFβ signaling pathway have been implicated in most human adenocarcinomas. In addition to its role in cancer cell migration and metastasis, TGFβ has been implicated in tumor‐mediated immunosuppression. Membrane‐bound TGFβ has previously been reported to be expressed on a subset of regulatory T cells and was shown to be critical to their immune suppressive function. In the present study, we document expression of a signaling competent, endogenously derived form of cell surface‐bound TGFβ on colorectal cancer cells. While antibodies against only the mature form of TGFβ failed to label cells, surface‐bound TGFβ was clearly detected by antibodies specific for both the latent and mature forms of the cytokine. Confirming the notion that the surface TGFβ was in latent form, brief acid pulsing of the cells increased the amount of detectable membrane‐associated TGFβ. In coculture assays, this cell‐bound TGFβ could be activated and utilized in a paracrine fashion both by other cancer cells and by CD8+ intraepithelial lymphocytes. This effect was abrogated by the use of a furin inhibitor which decreased the membranous expression of TGFβ on the tumor cells. Signaling competent membrane‐bound TGFβ on cancer cells is thus likely to be a key player in regulating tumor cell interactions with each other as well as with other cells in their microenvironment. © 2007 Wiley‐Liss, Inc.
Architecture of an in vivo‐tissue engineered autologous conduit “Biovalve”
Authors: Hayashida Kyoko , Kanda Keiichi , Oie Tomonori , Okamoto Yoshihiro , Ishibashi‐Ueda Hatsue , Onoyama Masaaki , Tajikawa Tsutomu , Ohba Kenkichi , Yaku Hitoshi , Nakayama Yasuhide
Published: December 2007

As a practical concept of regenerative medicine, we have focused on in vivo tissue engineering utilizing the foreign body reaction. Plastic substrates for valvular leaflet organization, consisting of two pieces assembled with a small aperture were inserted into a microporous polyurethane conduit scaffold. The assembly was placed in the subcutaneous spaces of Japanese white rabbits for 1 month. After the substrates were pulled out from the harvested implant, valve leaflet‐shaped membranous tissue was formed inside the tubular scaffold as designed. The valve leaflet was composed of the same collagen‐rich tissue, with the absence of any elastic fiber, as that which had ingrown or covered the scaffold. No abnormal collection or infiltration of inflammatory cells in the leaflet and the scaffold could be demonstrated. According to the immunohistochemical staining, the leaflet was comprised of numerous vimentin‐ or α‐SMA‐positive cells, corresponding to fibroblasts or myofibroblats, but contained no desmin‐positive cells. The analysis of the video data of the valve movement showed that, in synchronization with the backward flow in the diastolic phase, the valve closed rapidly and tightly and, in the transition phase of the flow direction, the valve opened smoothly without flapping or hitting the scaffold wall. Using mold designs, consisting of two different plastic substrates and the tubular scaffold, in conjunction with “in body tissue architecture,” the complex 3‐dimensional autologous conduit‐typed Biovalve was developed for the first time. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Effect of low intensity pulsed ultrasound on healing of an ulna defect filled with a bone graft substitute
Authors: Walsh William R. , Langdown Andrew J. , Auld Jason W. , Stephens Paul , Yu Yan , Vizesi Frank , Bruce Warwick J. M. , Pounder Neill
Published: December 2007

A 1.5 cm unilateral rabbit ulna defect model was performed in 18 adult NZ white rabbits. The defects were filled with a β‐tricalcium phosphate bone graft substitute (JAX TCP). The surgical site in half the animals was treated daily with 20 min of low intensity pulsed ultrasound (LIPUS). Animals were sacrificed at 4 weeks (n = 3 per group) or 12 weeks (n = 6 per group) following surgery for radiographic and histologic endpoints. Radiography revealed some resorption of the JAX TCP by 12 weeks in the control and LIPUS treated groups. LIPUS treatment did not accelerate this resorption. Some new bone formation was noted in the control groups at the defect margins while little bone formed in the center of the defect at 4 and 12 weeks. In contrast, radiographs revealed more new bone at 4 and 12 weeks in the LIPUS treated animals throughout the section. Bone mineral density (DEXA) revealed a statistically significant difference at 4 weeks with LIPUS while no differences were found at 12 weeks. Histology of the LIPUS treated sections demonstrated new woven bone formation on and between the JAX TCP bone graft substitute particles across the defect. VEGF expression was increased with LIPUS treatment at 4 weeks and remained elevated at 12 weeks compared with controls. CBFA‐1 expression levels were elevated with LIPUS treatment at both time points. LIPUS treatment increased bone formation in ulna defect healing with a β‐tricalcium phosphate bone graft substitute. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Hydrodynamics‐based delivery of plasmid DNA encoding CTLA4‐Ig prolonged cardiac allograft survival in rats
Authors: Takekubo Masaru , Tsuchida Masanori , Haga Manabu , Saitoh Masayuki , Hanawa Haruo , Maruyama Hiroki , Miyazaki Jun‐ichi , Hayashi Jun‐ichi
Published: December 2007

Background

Although gene therapy using plasmid vectors is thought to be safer compared with viral vectors, poor efficacy of gene transfer is the obstacle preventing wide application of plasmid vectors. However, high levels of foreign gene expression have been achieved by rapid tail vein injection of a large volume of a plasmid DNA solution into rats. Using this technique, we examined the effect of rat CTLA4‐Ig gene transfer on prevention of cardiac allograft rejection in this animal model.

Methods

Recipient Lewis rats were injected with either plasmid pCAGGS‐CTLA4‐Ig‐Glu‐tag as a treatment vector or plasmid pCAGGS‐signal peptide (SP)‐Ig as a control vector by hydrodynamics‐based delivery technique on the day before heart transplantation. Hearts from Brown Norway donors were transplanted into the neck of Lewis recipients and graft survival was assessed.

Results

The plasma level of CTLA4‐Ig reached a peak of nearly 5 µg/mL 1 day after injection, and then slowly decreased but still remained above 0.9 µg/mL until 100 days after injection. The recipient rats treated with the control vector and untreated rats rejected cardiac allografts within 7 days. On the other hand, the median survival time of the grafts treated with pCAGGS‐CTLA4Ig‐Glu‐tag was more than 100 days. Histological examination revealed that long‐term survival allografts contained fewer infiltrating lymphocytes. The serum from recipients with long‐term survival allograft suppressed allogenic mixed lymphocyte reaction.

Conclusions

CTLA4‐Ig gene transfer by means of tail vein injection of plasmid DNA into a recipient rat resulted in remarkable prolongation of cardiac allograft survival with persistent plasma level of CTLA4‐Ig protein. Copyright © 2007 John Wiley & Sons, Ltd.
Functional reconstruction and synthetic mimicry of a conformational epitope using CLIPS™ technology
Authors: Timmerman Peter , Puijk Wouter C. , Meloen Rob H.
Published: December 2007

This paper describes immunization studies with CLIPS‐constrained peptides covering only the major part (β3‐loop) of a structurally complex antigenic site on human Follicle Stimulating Hormone β‐subunit (FSH‐β). In cases where linear and SS‐constrained peptides fail, the CLIPS‐constrained peptides generate polyclonal antibodies with high neutralizing activity for hFSH. The sera were shown to be specific for hFSH over human Luteinizing Hormone (hLH) and human Chorionic Gonadotropin (hCG). ELISA‐competition studies and circular dichroism (CD)‐measurements illustrate clearly that activity of the peptides in antibody binding and generation relates directly to precise and appropriate fixation of the peptide conformation. Design of the CLIPS‐peptides was entirely based on epitope mapping studies with two neutralizing anti‐hFSH mAbs. Both mAbs were shown to bind to a conformational epitope located at the top of the β1−β3‐loop covering the amino acid sequences Y58‐P77 (β3‐loop). The results described in this paper show that CLIPS‐constrained peptides covering the Y58‐P77 sequence provide the minimally required structural entity necessary to generate reproducibly sera with high hFSH‐neutralizing activity. Copyright © 2007 John Wiley & Sons, Ltd.

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Survey of the year 2006 commercial optical biosensor literature
Authors: Rich Rebecca L. , Myszka David G.
Published: December 2007

We identified 1219 articles published in 2006 that described work performed using commercial optical biosensor platforms. It is interesting to witness how the biosensor market is maturing with an increased number of instrument manufacturers offering a wider variety of platforms. However, it is clear from a review of the results presented that the advances in technology are outpacing the skill level of the average biosensor user. While we can track a gradual improvement in the quality of the published work, we clearly have a long way to go before we capitalize on the full potential of biosensor technology. To illustrate what is right with the biosensor literature, we highlight the work of 10 groups who have their eye on the ball. To help out the rest of us who have the lights on but nobody home, we use the literature to address common myths about biosensor technology. Copyright © 2007 John Wiley & Sons, Ltd.
Maternal hyperthyroidism in rats impairs stress coping of adult offspring
Authors: Zhang Limei , Hernández Vito S. , Medina‐Pizarro Mauricio , Valle‐Leija Pablo , Vega‐González Arturo , Morales Teresa
Published: December 2007

Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced‐swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin‐releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood. © 2007 Wiley‐Liss, Inc.
Changes in monthly precipitation and flood hazard in the Yangtze River Basin, China
Authors: Jiang Tong , Kundzewicz Zbigniew W. , Su Buda
Published: December 2007

A study of change of meteorological and hydrological variables (precipitation, intense precipitation, and river flow) in the Yangtze River Basin was conducted for particular calendar months. Significant changes were found in many monthly precipitation datasets collected between 1961 and 2000. The strongest relative increase was detected in January, when the monthly precipitation is low in absolute terms. Changes in the monthly precipitation in spring and summer, from April to August, some of which are statistically significant, are of direct importance to seasonal flood hazard. The significant precipitation rise detected in June, July, and August tends to aggravate the flood hazard. Results of change detection in time series of intense precipitation in the Yangtze River Basin indicate that more precipitation falls in intense events at the expense of moderate and weak events. Significant upward trends in the discharge of the River Yangtze in summer months in the middle and lower regions were also detected. Finally, precipitation in the Yangtze River Basin and discharge in the mainstream Yangtze (gauges Yichang and Datong) in summer 1998 have been examined, in order to interpret the background of the catastrophic flood which is considered to be the costliest flood ever, worldwide. Copyright © 2007 Royal Meteorological Society
Cross‐border strategic alliances: co‐operation between firms from the United Arab Emirates and international partners
Authors: Butler Colin J.
Published: December 2007

The globalized business environment has accelerated the proliferation of cross‐border strategic alliances (SA). In 2007, firms in the United Arab Emirates are depending on sales in export markets more in order to make investments in industry viable in the short term and profitable in the long term.

Emirati managers of cross‐border strategic alliances need different skills and a different attitude from their predecessors in order to meet the new challenges being posed by changes in the global business environment.

Copyright © 2007 John Wiley & Sons, Ltd.
Gas‐phase pyrolytic reaction of 3‐phenoxy and 3‐phenylsulfanyl‐1‐propanol derivatives: Kinetic and mechanistic study
Authors: Dib H. H. , Ibrahim M. R. , Al‐Awadi N. A. , Ibrahim Y. A. , Al‐Awadi S.
Published: December 2007

3‐Phenoxy‐1‐propanols 1a–c and 3‐phenylsulfanyl‐1‐propanols 2a–c containing primary, secondary, and tertiary alcohols were prepared and subjected to gas‐phase pyrolysis in a static reaction system. Pyrolysis of 4‐phenyl‐1‐butanol 3, 2‐methyl‐3‐phenyl‐1‐propanol 4, and 2‐methyl‐3‐phenylpropanoic acid 5 was also studied, and results were compared with those obtained for compounds 1–3. The pyrolytic reactions were homogeneous and followed a first‐order rate equation. Analysis of the pyrolysate showed the products to be phenol (from 1a to 1c), thiophenol (from 2a to 2c), and toluene (from 3 to 5) and carbonyl compounds. The kinetic results and product analysis of each of the nine investigated compounds are rationalized in terms of a plausible transition state for the elimination pathway. © 2007 Wiley Periodicals, Inc. 40: 51–58, 2008
Effects of unidirectional and mutual interactions between microstructures and azo dyes as “kinetic” probe molecules on cis→trans isomerization rate constants in aqueous P85 and F88 triblock copolymer solutions
Authors: Knoll Helmut
Published: December 2007

Rate constants of the thermal cis → trans isomerization of azo dyes have been studied in aqueous P85 and F88 triblock copolymer solutions by means of microsecond flash photolysis. Inflection points or maxima of the nonlinear Arrhenius plots indicate microstructure changes around the “kinetic” probe molecules. Unidirectional interactions of micelle formation on reactivity are reflected by discontinuous change of rate constants at temperatures near the critical micellization temperatures (cmT) determined by means of probe‐free methods. Mutual interactions have been identified by means of significant differences between cmT and temperatures, where rate constants change discontinuously. The type of interactions depends on the properties of probe molecules and amphiphiles. Systems as studied in this work might be models of more complex biological reaction systems with temperature‐dependent microstructure changes. © 2007 Wiley Periodicals, Inc. 40: 59–65, 2007
Rhinorrhea is increased in Parkinson's disease
Authors: Friedman Joseph H. , Amick Melissa M.
Published: December 2007

We have observed that rhinorrhea is increased in people with Parkinson's disease (PD) but only a single publication supports this. We performed two separate case control studies to assess the prevalence of rhinorrhea in PD in Rhode Island. One was cross‐sectional and the other in consecutive de novo patients. We further questioned subjects as to whether rhinorrhea might be associated with olfactory impairment. We found that rhinorrhea affects about half of PD patients in Rhode Island, is an early feature, being present at the time of presentation, was significantly more common than in controls and was associated with self‐perceived reduced olfaction. These observations confirm that rhinorrhea is a common problem and raise the questions as to whether some olfactory impairment found in PD could be confounded by rhinorrhea and also whether rhinorrea may be a premotor symptom. © 2007 Movement Disorder Society
A teenage boy with late onset hemophagocytic lymphohistiocytosis with predominant neurologic disease and perforin deficiency
Authors: Beaty Andrew D. , Weller Christin , Levy Beth , Vogler Carole , Ferguson William S. , Bicknese Alma , Knutsen Alan P.
Published: December 2007

Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive disorder of cytotoxic cell function that results in abnormal proliferation of benign lymphocytes and histiocytes in response to infectious stimuli. FHLH generally occurs in very young children, and typically presents with fever, cytopenias, coagulopathy, lymphadenopathy, and hepatosplenomegaly. Central nervous system involvement occurs frequently and may precede the development of systemic symptoms by months to years. We report a case of an 18‐year‐old male with a 2‐year history of symptoms attributed to a demyelinating disorder, who succumbed to rapidly progressive hemophagocyte lymphohistiocytosis. Post‐mortem, two distinct perforin mutations were identified. We discuss the central nervous system and genetic findings in this unusual presentation of familial hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2008;50:1070–1072. © 2007 Wiley‐Liss, Inc.
Altered expression of genes regulating angiogenesis in experimental androgen‐independent prostate cancer
Authors: Gustavsson Heléne , Jennbacken Karin , Welén Karin , Damber Jan‐Erik
Published: December 2007

BACKGROUND

The aim of this study was to investigate how the expression of genes regulating angiogenesis is altered when prostate cancer cells progress into androgen‐independency.

METHODS

A gene array specific for angiogenesis was used to compare the human prostate cancer cell line LNCaP (androgen‐dependent) with its more angiogenic and tumorigenic subline LNCaP‐19 (androgen‐independent). Results were verified with real‐time RT‐PCR, and further investigations were focused on the angiogenesis inhibitor a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Expression of ADAMTS1 was investigated in vitro as well as in subcutaneous tumors with real‐time RT‐PCR and Western blotting. Microvessel density (MVD), versican proteolysis and protein levels of TIMP‐2 and TIMP‐3, known as ADAMTS1 inhibitors, were also analyzed in tumor xenografts.

RESULTS

The gene array revealed decreased expression of ADAMTS1, ephrin‐A5, fibronectin 1, and neuropilin 1 in LNCaP‐19 compared to LNCaP, while expression of midkine and VEGF were increased. Further studies showed that mRNA and protein levels of ADAMTS1 were significantly lower in LNCaP‐19 compared to LNCaP, both in vitro and in subcutaneous tumors. The amount of ADAMTS1 correlated negatively with MVD, but no relation was found between ADAMTS1 and versican proteolysis.

CONCLUSIONS

Expression of several genes associated with angiogenesis was altered during transition into androgen‐independency. Among these, a significant decrease was found for ADAMTS1, whose expression inversely correlated with MVD. Its role in progression of prostate cancer needs further investigation, but this inhibitor of angiogenesis could be an interesting candidate for future anti‐angiogenic therapy. Prostate 68: 161–170, 2008. © 2007 Wiley‐Liss, Inc.
A statistical rescoring scheme for protein–ligand docking: Consideration of entropic effect
Authors: Lee Juyong , Seok Chaok
Published: December 2007

Computational prediction of protein–ligand binding modes provides useful information on the relationship between structure and activity needed for drug design. A statistical rescoring method that incorporates entropic effect is proposed to improve the accuracy of binding mode prediction. A probability function for two sampled conformations to belong to the same broad basin in the potential energy surface is introduced to estimate the contribution of the state represented by a sampled conformation to the configurational integral. The rescoring function is reduced to the colony energy introduced by Xiang et al. (Proc Natl Acad Sci USA 2002;99:7432–7437) when a particular functional form for the probability function is used. The scheme is applied to rescore protein–ligand complex conformations generated by AutoDock. It is demonstrated that this simple rescoring improves prediction accuracy substantially when tested on 163 protein–ligand complexes with known experimental structures. For example, the percentage of complexes for which predicted ligand conformations are within 1 Å root‐mean‐square deviation from the native conformations is doubled from about 20% to more than 40%. Rescoring with 11 different scoring functions including AutoDock scoring functions were also tested using the ensemble of conformations generated by Wang et al. (J Med Chem 2003;46:2287–2303). Comparison with other methods that use clustering and estimation of conformational entropy is provided. Examination of the docked poses reveals that the rescoring corrects the predictions in which ligands are tightly fit into the binding pockets and have low energies, but have too little room for conformational freedom and thus have low entropy. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Using quantum mechanics to improve estimates of amino acid side chain rotamer energies
Authors: Renfrew P. Douglas , Butterfoss Glenn L. , Kuhlman Brian
Published: December 2007

Amino acid side chains adopt a discrete set of favorable conformations typically referred to as rotamers. The relative energies of rotamers partially determine which side chain conformations are more often observed in protein structures and accurate estimates of these energies are important for predicting protein structure and designing new proteins. Protein modelers typically calculate side chain rotamer energies by using molecular mechanics (MM) potentials or by converting rotamer probabilities from the protein database (PDB) into relative free energies. One limitation of the knowledge‐based energies is that rotamer preferences observed in the PDB can reflect internal side chain energies as well as longer‐range interactions with the rest of the protein. Here, we test an alternative approach for calculating rotamer energies. We use three different quantum mechanics (QM) methods (second order Møller‐Plesset (MP2), density functional theory (DFT) energy calculation using the B3LYP functional, and Hartree‐Fock) to calculate the energy of amino acid rotamers in a dipeptide model system, and then use these pre‐calculated values in side chain placement simulations. Energies were calculated for over 36,000 different conformations of leucine, isoleucine, and valine dipeptides with backbone torsion angles from the helical and strand regions of the Ramachandran plot. In a subset of cases these energies differ significantly from those calculated with standard molecular mechanics potentials or those derived from PDB statistics. We find that in these cases the energies from the QM methods result in more accurate placement of amino acid side chains in structure prediction tests. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Predicting protein homocysteinylation targets based on dihedral strain energy and pKa of cysteines
Authors: Sundaramoorthy Elayanambi , Maiti Souvik , Brahmachari Samir K. , Sengupta Shantanu
Published: December 2007

A multitude of complex diseases have been linked to elevated homocysteine levels; however, till date there is no plausible explanation for a single amino acid's involvement in so many diseases. Since homocysteine is a reactive thiol amino acid and the majority of plasma homocysteine is protein thiol bound, we hypothesized that homocysteine might bind to accessible cysteine residues in target proteins, thereby modulating its structure or function or both. The parameters that dictate homocysteine–protein interaction are not well understood, and the few known homocysteine binding proteins wereidentified by a candidate protein approach. In this study, we identified potential homocysteine interacting proteins based on cysteine content, solvent accessibility of cysteine residues, and dihedral strain energies and pKa of these cysteines. Pathway mapping of the cysteine‐rich proteins revealed that proteins in the coagulation cascade, notch receptor‐mediated signaling, LDL endocytosis, programmed cell death, and extracellular matrix proteins were significantly over‐represented with cysteine‐rich proteins, and we believe that homocysteine has a high probability to bind to proteins in these pathways. In fact, several clinical studies have implicated high homocysteine levels to be associated with diseases like thrombosis, neural tube defects, and so forth, which result from dysfunction of one or more of the proteins identified in our study. Further, we successfully validated our prediction parameters on the proteins that have already been experimentally shown to bind homocysteine, and our structural analysis argues a plausible explanation for these prior reported protein interactions with homocysteine that could not be previously explained. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Binding of sulfonium‐ion analogues of di‐epi‐swainsonine and 8‐epi‐lentiginosine to Drosophila Golgi α‐mannosidase II: The role of water in inhibitor binding
Authors: Kumar Nag S. , Kuntz Douglas A. , Wen Xin , Pinto B. Mario , Rose David R.
Published: December 2007

Retaining glycosidases operate by a two‐step catalytic mechanism in which the transition states are characterized by buildup of a partial positive charge at the anomeric center. Sulfonium‐ion analogues of the naturally occurring glycosidase inhibitors, swainsonine and 8‐epi‐lentiginosine, in which the bridgehead nitrogen atom is replaced by a sulfonium‐ion, were synthesized in order to test the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor. Initial prediction based on computational docking indicated three plausible binding modes to Drosophila Golgi α‐mannosidase II (dGMII), the most likely being close to that of swainsonine. Observation of the binding of di‐epi‐thioswainsonine and 8‐epi‐thiolentiginosine to dGMII from crystallographic data, however, revealed an orientation different from swainsonine in the active site. Screening these two compounds against dGMII shows that they are inhibitors with IC50 values of 2.0 and 0.014 mM, respectively. This dramatic difference in affinity between the two compounds, which differ by only one hydroxyl group, is rationalized in terms of bound water molecules and the water molecule substructure in the active site, as identified by comparison of high resolution X‐ray crystal structures of several dGMII‐inhibitor complexes. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Exploring the protein G helix free‐energy surface by solute tempering metadynamics
Authors: Camilloni Carlo , Provasi Davide , Tiana Guido , Broglia Ricardo A.
Published: December 2007

The free‐energy landscape of the α‐helix of protein G is studied by means of metadynamics coupled with a solute tempering algorithm. Metadynamics allows to overcome large energy barriers, whereas solute tempering improves the sampling with an affordable computational effort. From the sampled free‐energy surface we are able to reproduce a number of experimental observations, such as the fact that the lowest minimum corresponds to a globular conformation displaying some degree of β‐structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a π‐helix state and that the hydrophobic staple motif is present only in the free‐energy minimum associated with the helices, and contributes to their stabilization. The use of metadynamics coupled with solute tempering results then particularly suitable to provide the thermodynamics of a short peptide, and its computational efficiency is promising to deal with larger proteins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Huntingtin interacting protein HYPK is intrinsically unstructured
Authors: Raychaudhuri Swasti , Majumder Pritha , Sarkar Somosree , Giri Kalyan , Mukhopadhyay Debashis , Bhattacharyya Nitai P.
Published: December 2007

To characterize HYPK, originally identified as a novel huntingtin (Htt) interacting partner by yeast two hybrid assay, we used various biophysical and biochemical techniques. The molecular weight of the protein, determined by gel electrophoresis, was found to be about 1.3‐folds (∼22 kDa) higher than that obtained from mass spectrometric analysis (16.9 kDa). In size exclusion chromatography experiment, HYPK was eluted in three fractions, the hydrodynamic radii for which were calculated to be ∼1.5‐folds (23.06 Å) higher than that expected for globular proteins of equivalent mass (17.3 Å). The protein exhibited predominantly (63%) random coil characteristics in circular dichroism spectroscopy and was highly sensitive to limited proteolysis by trypsin and papain, indicating absence of any specific domain. Experimental evidences with theoretical analyses of amino acids composition of HYPK and comparison with available published data predicts that HYPK is an intrinsically unstructured protein (IUP) with premolten globule like conformation. In presence of increasing concentration of Ca2+, HYPK showed conformational alterations as well as concomitant reduction of hydrodynamic radius. Even though any link between the natively unfolded nature of HYPK, its conformational sensitivity towards Ca2+ and interaction with Htt is yet to be established, its possible involvement in Huntington's disease pathogenesis is discussed. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Low‐voltage, high‐gain, and high‐mobility organic complementary inverters based on N,N′‐ditridecyl‐3,4,9,10‐perylenetetracarboxylic diimide and pentacene
Authors: Tatemichi Shuhei , Ichikawa Musubu , Kato Shimpei , Koyama Toshiki , Taniguchi Yoshio
Published: December 2007

The authors describe an organic complementary inverter with N,N′‐ditridecyl‐3,4,9,10‐perylenetetracarboxylic diimide as an n‐type semiconductor and pentacene as a p‐type semiconductor. Each transistor of the inverter exhibited high carrier mobility: 1.62 cm2/Vs for an n‐type drive transistor and 0.57 cm2/Vs for a p‐type switch transistor. The gain of the inverter reached 125. Another inverter using Ta2O5 as a high κ gate dielectric performed well with a gain of 500 and an operation voltage of only 5 V.

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(© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Carbon Fiber Composite Targets for Nuclear Fusion Technology: A Focused Ion Beam/Scanning Electron Microscope Investigation
Authors: Ghezzi F. , Magni S. , Milani M. , Tatti F.
Published: December 2007

Carbon fiber composite (CFC) targets are investigated by a focused ion beam/scanning electron microscope (FIB/SEM) in a joint project aiming at the development of robust divertors in the International Thermonuclear Experimental Reactor (ITER). These mockups are exposed to a plasma that simulates the off‐normal thermal loads foreseen for ITER and display a rich, puzzling impact scenario. Morphological elements are identified at the exposed surface and beneath it, and are examined in order to point out the relevant processes involved. Each technique adopted is discussed and evaluated. SCANNING 29: 254–260, 2007. © 2007 Wiley Periodicals, Inc.
Use of positive reinforcement conditioning to monitor pregnancy in an unanesthetized snow leopard (Uncia uncia) via transabdominal ultrasound
Authors: Broder Jacqueline M. , MacFadden Annabell J. , Cosens Lindsay M. , Rosenstein Diana S. , Harrison Tara M.
Published: December 2007

Closely monitoring snow leopard (Uncia uncia) fetal developments via transabdominal ultrasound, with minimal stress to the animal, was the goal of this project. The staff at Potter Park Zoo has used the principles of habituation, desensitization, and positive reinforcement to train a female snow leopard (U. uncia). Ultrasound examinations were preformed on an unanesthetized feline at 63 and 84 days. The animal remained calm and compliant throughout both procedures. Fetuses were observed and measured on both occasions. The absence of anesthesia eliminated components of psychologic and physiologic stress associated with sedation. This was the first recorded instance of transabdominal ultrasound being carried out on an unanesthetized snow leopard. It documents the feasibility of detecting pregnancy and monitoring fetal development via ultrasound. Zoo Biol 27:78–85, 2008. © 2007 Wiley‐Liss, Inc.
Five-Year Survival in a Cohort of Hip Fracture Patients: The Predictive Role of Pre-fracture Health Status
Authors: Peterson Margaret G. E. , Cornell Charles N. , Paget Stephen A. , Allegrante John P.
Published: December 2007

The aim was to assess the outcome of surgery at 5 years after hip fracture. In this prospective study, we analyzed 5-year survival of a cohort of 105 hip fracture patients as a function of preoperative health. The main outcome measurements were the status of the patient, dead or alive, and the SF-36 of their pre-fracture status as recalled during their hospital stay. In the fifth year post-hospitalization 58 patients were alive. There was a significant association between the recall SF-36 general health score and being alive in the fifth year ( P = 0.0004) and with survival in general ( P = 0.0001). This and prior studies support the concept of stratifying hip fracture patients according to pre-fracture health status when assessing outcomes of fracture repair or other interventions. This study further demonstrates the utility of the SF-36 for this purpose.
Risks Associated with Exposure to Surgical Smoke Plume: A Review of the Literature
Authors: Bigony Lorraine
Published: December 2007

ELECTROSURGERY, LASER ABLATION, and ultrasonic scalpel dissection create a gaseous by‐product commonly referred to as surgical smoke or plume.

SMOKE EVACUATION DEVICES have been shown to be effective in limiting exposure to the noxious odor and potential health hazards of smoke and plume; however, these devices have not been used routinely and consistently in many ORs.

THIS ARTICLE REVIEWS FIVE QUANTITATIVE research studies that explore the characteristics of smoke plume produced during surgery and presents the evidence of the need for consistent use of smoke evacuation systems. AORN J 86 (December 2007) 1013‐1020. © AORN, Inc, 2007.
Book Reviews
Authors: Scherffius Jo Ann , Battalora Elizabeth A. , Zuber Jennifer , Davidson‐Wilson Latanya D. , Davis Rebecca J.
Published: December 2007

Bob Wall 2006, 256 pages. $24.95 hardcover

Brian Tracy 2006, 128 pages$17.95 hardcover

B. Joseph White with Yaron Prywes 2006, 192 pages $21.95 hardcover

Donna Deeprose 2006, 144 pages $13.95 softcover

Gerard H. (Gus) Gaynor 2004, 256 pages $17.95 softcover
The Effects of Electronic Documentation in the Ambulatory Surgery Setting
Authors: O'Meara Estela
Published: December 2007

ELECTRONIC DOCUMENTATION can improve organizational processes in health care settings and may be of particular benefit to ambulatory surgery centers.

A DECISION SUPPORT SYSTEM (DSS) can be integrated with an electronic documentation system. A DSS can identify potential errors and deviations from best practices and provide electronic alerts for health care clinicians to support patient screening and care.

BARRIERS TO IMPLEMENTATION of a DSS include practitioner noncompliance with alerts and limitations in system design.

NURSES CAN BE INSTRUMENTAL in overcoming the barriers that prevent some clinicians from adopting these useful information systems. AORN J 86 (December 2007) 970–979. © AORN, Inc, 2007.
Alternative mRNA splicing of SAP30L regulates its transcriptional repression activity
Authors: Korkeamäki Hanna , Viiri Keijo , Kukkonen Mari K. , Mäki Markku , Lohi Olli
Published: December 2007

Covalent modification of histones regulates chromatin structure and gene expression. Sin3A mediates the association of histone deacetylase enzymes with a large number of sequence‐specific transcriptional repressors. In this study we characterized three novel transcripts of SAP30L, a recently identified Sin3A‐associated protein. These splice variants show significant differences in transcriptional repression capabilities and associating histone deacetylase activities. Furthermore, they differ in binding to Sin3A and in subcellular localization when transiently transfected. These data suggest that the transcriptional repression of a Sin3A corepressor complex can be regulated not only by sequence‐specific transcriptional repressors, but also by modification of associated proteins, such as SAP30L.
Correlation between Shiga toxin B‐subunit stability and antigen crosspresentation: A mutational analysis
Authors: Pina David G. , Stechmann Bahne , Shnyrov Valery L. , Cabanié Lucien , Haicheur Nacilla , Tartour Eric , Johannes Ludger
Published: December 2007

The homopentameric B‐subunit of Shiga toxin (STxB) is used as a tool to deliver antigenic peptides and proteins to the cytosolic compartment of dendritic cells (DCs). In this study, a series of interface mutants of STxB has been constructed. All mutants retained their overall conformation, while a loss in thermal stability was observed. This effect was even more pronounced in trifluoroethanol solutions that mimic the membrane environment. Despite this, all mutants were equally efficient at delivering a model antigenic protein into the MHC class I‐restricted antigen presentation pathway of mouse DCs, suggesting that the structural stability of STxB is not a key factor in the membrane translocation process.