bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of bone and soft tissue sarcoma after radiotherapy: A cohort study of 295,712 Finnish cancer patients
Authors: Virtanen Anna , Pukkala Eero , Auvinen Anssi
Published: September 2005

Radiotherapy is commonly used for treatment of malignant disease. As a consequence of radiotherapy, an increased risk of developing a second malignant neoplasm has been shown. However, little is known about the effects of radiation on developing sarcoma. The aim of this study was to examine the risk of developing a bone or soft tissue sarcoma after radiotherapy for a first primary cancer. The study population included all the patients with primary cancers of breast, cervix uteri, corpus uteri, lung, ovary, prostate, rectum and lymphoma diagnosed during 1953–2000 and identified from the Finnish Cancer Registry. Patients were followed up for subsequent sarcomas. The follow‐up yielded 1.5 million person‐years at risk and 147 sarcomas. Compared to the national incidence rates, after 10 years of follow‐up sarcoma risk was increased among patients who had received neither radiotherapy nor chemotherapy (standardised incidence ratio (SIR) 2.0, 95% CI 1.3–3.0), radiotherapy without chemotherapy (SIR 3.2, 95% CI 2.3–4.3), chemotherapy without radiotherapy (SIR 4.9, 95% CI 1.0–14.4), as well as combined radiotherapy and chemotherapy (SIR 3.4, 95% CI 0.4–12.5). For radiotherapy in ages below 55 the SIR was 4.2 (95% CI 2.9–5.8). In the adjusted regression analysis the rate ratio was 1.5 (95% CI 0.9–2.6) for the radiotherapy group. In conclusion, radiotherapy appears to be associated with an increased risk of developing sarcoma especially among younger patients. Further investigation is needed to clarify the dose–response of the preceding ionizing radiation. © 2005 Wiley‐Liss, Inc.
Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF‐7 xenografts in ovariectomized athymic nude mice
Authors: Power Krista A. , Saarinen Niina M. , Chen Jian Min , Thompson Lilian U.
Published: September 2005

This study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF‐7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF‐7 tumors were fed a basal diet (AIN‐93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response. In the ENL‐ and END‐treated mice, palpable tumors regressed significantly by 91 and 83%, respectively, resulting in final tumors that were similar to the negative control tumors. However, tumor cell apoptosis was significantly enhanced by the lignans. In the GEN‐treated mice, tumors initially regressed significantly by 64% but regression ceased following prolonged treatment, resulting in final tumors that were significantly larger compared to negative control, ENL‐, and END‐treated mice, in part by increasing tumor cell proliferation. The MIX treatment significantly regressed palpable tumors by 87% similar to negative control group, with no effects on tumor cell apoptosis or proliferation. The isoflavone GEN alone promoted the growth of established MCF‐7 human breast cancer xenografts after prolonged treatment while the mammalian lignans ENL and END did not. When these phytoestrogens were given in combination, no tumor growth‐promoting effects were observed. © 2005 Wiley‐Liss, Inc.
Hormonal and reproductive factors and risk of glioma: A prospective cohort study
Authors: Silvera Stephanie A. Navarro , Miller Anthony B. , Rohan Thomas E.
Published: September 2005

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. Given the lower incidence rate of glioma in women than in men, it has been hypothesized that reproductive and hormonal factors may be involved in the etiology of glioma. We conducted a secondary analysis of data from the National Breast Screening Study, which included 89,835 Canadian women, aged 40–59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow‐up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between hormonal and reproductive factors and risk of glioma. During a mean of 16.4 years of follow‐up, we observed 120 incident glioma cases. Compared with women with a relatively early age at menarche (≤12 years), women who were 13–14 years of age at menarche had a 64% increased risk of glioma (95% CI = 1.01–2.65), and women who were older than 14 years of age at menarche had a 66% increased risk of glioma (95% CI = 0.86–3.20, ptrend = 0.06). Age at first live birth, parity, menopausal status, use of oral contraceptive and use of hormone replacement therapy were not associated with altered glioma risk in our study population. Additional prospective studies are needed to confirm our findings. © 2005 Wiley‐Liss, Inc.
Antigen‐independent accumulation of activated effector/memory T lymphocytes into human and murine tumors
Authors: Joncker Nathalie T. , Marloie Marie‐Annick , Chernysheva Anna , Lonchay Christophe , Cuff Simone , Klijanienko Jerzy , Sigal‐Zafrani Brigitte , Vincent‐Salomon Anne , Sastre Xavier , Lantz Olivier
Published: September 2005

Tumor infiltrating lymphocytes (TIL) display activation markers and their presence is often associated with a favorable outcome. The role of tumor antigens in T cell recruitment into tumors is unclear. In an attempt to address this issue, we purified lymphocytes from breast tumor or nontumor, mammary tissue from patients, and normal mammary tissue from healthy individuals. In all groups, including healthy individuals, the majority of cells displayed an effector/memory (CD45RAlo/CD27+/−) phenotype and quite surprisingly the early and transient activation marker CD69, thus, questioning the tumor antigen specificity of TIL. Because the human repertoire is diverse, the T cells found in the tumors could recognize both self/tumor and environmental antigens through cross‐reactivity. To test this hypothesis, we used two anti‐male HY monospecific TCR transgenic mouse models. We found an infiltration of HY negative tumors by the CD4+ and CD8+ monoclonal T cells after priming with HY positive cells in the periphery. Thus, the presence of activated effector/memory T lymphocytes in tumors can be independent of reactivity against tumor antigens. These results suggest that to find activated effector T cells in a tissue does not always mean that a specific immune response is taking place. © 2005 Wiley‐Liss, Inc.
Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case–control study
Authors: Cirincione Rosalia , Lintas Carla , Conte Davide , Mariani Luigi , Roz Luca , Vignola Antonio Maurizio , Pastorino Ugo , Sozzi Gabriella
Published: September 2005

We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RARβ2, p16INK4A and RASSF1A genes was evaluated by methylation‐specific PCR in tumor samples of 29 CT‐detected lung cancer patients, of which 18 had tumor‐sputum pairs available for the analysis, and in the sputum samples from 112 cancer‐free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT‐detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RARβ2, 12/29 (41.4%) for p16INK4A and 15/29 (51.7%) for RASSF1A. Twenty‐three of twenty‐nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RARβ2 and 1/18 (5%) for both RASSF1A and p16INK4A. At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer‐free smokers was observed in 58/112 (51.7%) for RARβ2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RARβ2, p16INK4A and RASSF1A promoters is present in spiral CT‐detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection. © 2005 Wiley‐Liss, Inc.
Risk assessment for biochemical recurrence prior to radical prostatectomy: Significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA‐elevation in serum
Authors: Steuber Thomas , Vickers Andrew J. , Haese Alexander , Becker Charlotte , Pettersson Kim , Chun Felix K.‐H. , Kattan Michael W. , Eastham James A. , Scardino Peter T. , Huland Hartwig , Lilja Hans
Published: September 2005

Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate‐specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate‐specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this “base” model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA ≤ 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA ≤ 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap‐corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA‐elevation (tPSA ≤ 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756–0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for “moderately elevated” PSA. For patients with a moderate tPSA‐elevation (tPSA ≤ 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR‐prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR. © 2005 Wiley‐Liss, Inc.
Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma
Authors: Fernebro Josefin , Francis Princy , Edén Patrik , Borg Åke , Panagopoulos Ioannis , Mertens Fredrik , Vallon‐Christersson Johan , Åkerman Måns , Rydholm Anders , Bauer Henrik CF , Mandahl Nils , Nilbert Mef
Published: September 2005

We applied 27k spotted cDNA microarray slides to assess gene expression profiles in 26 samples from 24 patients with synovial sarcomas (SS). The data were analyzed in relation to histopathologic type, cytogenetic aberrations, gene fusion type and development of distant metastases. Supervised analysis based on gene fusion type in 12 SS with SS18/SSX1 and 9 with SS18/SSX2 revealed significant differences in gene expression profiles. Among the discriminators were several genes that have previously been found to be upregulated in SS, including AXL, ZIC2, SPAG7, AGRN, FOXC1, NCAM1 and multiple metallothioneins. Histopathology and degree of cytogenetic complexity did not significantly influence expression, whereas a genetic signature that related to development of metastases could be discerned, albeit with a high false‐positive rate. In conclusion, our findings demonstrate differentially expressed genes for the 2 major gene fusion variants in SS, SS18/SSX1 and SS18/SSX2, and thereby suggest that these result in different downstream effects. © 2005 Wiley‐Liss, Inc.
Cross‐sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia
Authors: Flores Roberto , Papenfuss Mary , Klimecki Walter T. , Giuliano Anna R.
Published: September 2005

In human papillomavirus (HPV)‐associated carcinogenesis, HPV infection characteristics such as viral load may play an important role in lesion development. The purpose of this study was to determine the association between quantitative assessment of oncogenic HPV viral load, and abnormal cytology among women residing along the United States–Mexico border. A cross‐sectional study of 2,319 women was conducted between 1997 and 1998. Viral load of oncogenic HPV types (16, 18, 31, 39, 45, 51, 52, and 58) was measured among 173 HPV (+) women using quantitative real‐time PCR. Overall, HPV 16, 31, 52 and 58 showed the highest viral load. Single type infection had higher viral loads compared to multiple type infections. HPV viral load declined significantly (p = 0.04) with age. No significant association was observed with other known HPV risk factors such as oral contraceptive use, parity, sexual and STD history. Viral load was independently associated with degree of cervical lesions. An adjusted odds ratio (AOR) of 4.7 for the association between increasing total viral load and Atypical Squamous Cells of Undetermined Significance (ASCUS)/Atypical Glandular Cells of Undetermined Significance (AGUS) was observed (p for trend <0.01). Increased risk of low‐grade SIL was observed with higher viral load compared with HPV negative women (AOR = 47.7 for total viral load; AOR = 37.1 for HPV viral load not including HPV16, and AOR = 25.9 for HPV16 viral load). Likewise, increased risk of high‐grade SIL with higher viral loads was observed (AOR = 58.4 for high total viral load compared with HPV negative women, AOR = 58.1 for HPV viral load not including HPV16, and AOR = 69.8 for HPV16 high viral load). Results from this study suggest a dose–response relationship between increasing oncogenic HPV viral load and risk of LSIL and HSIL. © 2005 Wiley‐Liss, Inc.
Signalling responses linked to betulinic acid‐induced apoptosis are antagonized by MEK inhibitor U0126 in adherent or 3D spheroid melanoma irrespective of p53 status
Authors: Rieber Manuel , Rieber Mary Strasberg
Published: September 2005

MEK1/2 inhibitors like U0126 can potentiate or antagonize the antitumor activity of cytotoxic agents such as cisplatin, paclitaxel or vinblastine, depending on the drug or the target cells. We now investigated whether U0126, differentially regulates melanoma signaling in response to UV radiation or betulinic acid, a drug lethal against melanoma. This report shows that U0126 inhibits early response (ERK) kinase activation and cyclin A expression in wt p53 C8161 melanoma exposed to either UV radiation or betulinic acid. However, U0126 does not protect from UV damage, but counteracts betulinic acid‐mediated apoptosis in the same cells. Protection from the latter drug by joint treatment with U0126 was also evident in wt p53 MelJuso melanoma and mutant p53 WM164 melanoma. The latter cells were the most responsive to betulinic acid, showing a selective decline in the cdk4 protein, without a comparable change in other key cell cycle proteins like cdc2, cdk2, cdk7 or cyclin A, prior to apoptosis‐associated PARP fragmentation. Laser scanning cytometry also showed that betulinic acid induced a significant increase in chromatin condensation in WM164 melanoma irrespective of whether they were in adherent form or as multicellular spheroids. All these betulinic acid‐induced changes were counteracted by U0126. Our data show for the first time that (a) cdk4 protein is an early target of betulinic acid‐induced apoptosis and (b) unrestricted ERK signaling favours betulinic acid‐induced apoptosis, but this is counteracted by U0126, partly through counteracting chromatin condensation and restoring Akt activation decreased by betulinic acid treatment. © 2005 Wiley‐Liss, Inc.
Epidermal growth factor receptor and angiogenesis: Opportunities for combined anticancer strategies
Authors: van Cruijsen Hester , Giaccone Giuseppe , Hoekman Klaas
Published: September 2005

Tumor‐induced angiogenesis is essential for malignant growth. This mini review focuses on the role of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) and their receptors in this process, and the rationale to combine inhibitors of these growth factors as anticancer therapy. Concomitantly, targeting the VEGF(R) and the EGF(R) signaling pathway may circumvent the problem of acquired resistance to EGFR inhibitors. By targeting both pathways, the antiangiogenic effect may be more pronounced, which may lead to greater antitumor activity. Preliminary efficacy data from clinical trials encourage further exploration of this combined anticancer strategy. © 2005 Wiley‐Liss, Inc.
Atorvastatin stimulates the production of osteoprotegerin by human osteoblasts
Authors: Viereck Volker , Gründker Carsten , Blaschke Sabine , Frosch Karl‐Heinz , Schoppet Michael , Emons Günter , Hofbauer Lorenz C.
Published: September 2005

Recently, HMG‐CoA reductase inhibitors (statins), potent inhibitors of cholesterol biosynthesis, have been linked to protective effects on bone metabolism. Because of their widespread use, prevention of bone loss and fractures would be a desirable side effect. However, the mechanisms how statins may affect bone metabolism are poorly defined. Here, we evaluated the effect of atorvastatin on osteoblastic production of receptor activator of nuclear factor‐κB ligand (RANKL) and osteoprotegerin (OPG), cytokines that are essential for osteoclast cell biology. While RANKL enhances osteoclast formation and activation, thereby, promoting bone loss, OPG acts as a soluble decoy receptor and antagonizes the effects of RANKL. In primary human osteoblasts (hOB), atorvastatin increased OPG mRNA levels and protein secretion by hOB by up to three fold in a dose‐dependent manner with a maximum effect at 10−6 M (P < 0.001). Time course experiments indicated a time‐dependent stimulatory effect of atorvastatin on OPG mRNA levels after 24 h and on OPG protein secretion after 48–72 h (P < 0.001). Treatment of hOB with substrates of cholesterol biosynthesis that are downstream of the HMG‐CoA reductase reaction (mevalonate, geranylgeranyl pyrophosphate) reversed atorvastatin‐induced enhancement of OPG production. Of note, atorvastatin abrogated the inhibitory effect of glucocorticoids on OPG production. Treatment of hOB with atorvastatin enhanced the expression of osteoblastic differentiation markers, alkaline phosphatase and osteocalcin. In summary, our data suggest that atorvastatin enhances osteoblastic differentiation and production of OPG. This may contribute to the bone‐sparing effects of statins. © 2005 Wiley‐Liss, Inc.
Morphology and Thermal Properties of MCPA6/ABS by in situ Polymerization of ε‐Caprolactam
Authors: Hou Lianlong , Yang Guisheng
Published: September 2005

Summary: In this work, blends of monomer casting polyamide 6 (MCPA6) and acrylonitrile‐butadiene‐styrene (ABS) were successfully prepared by in situ polymerization via the application of ε‐caprolactam as a reactive solvent. The morphology and thermal properties of MCPA6/ABS were investigated by means of wide angle X‐ray diffraction (WAXD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), respectively. The domain sizes of the ABS phase in MCPA6/ABS blends were much finer than those in corresponding polyamide 6 (PA6)/ABS blends prepared by simple melt blending. With an increased amount of ABS in MCPA6, the melt enthalpy (ΔHf), the rate of crystallization (Tc) and the degree of crystallinity (Xc(DSC)) of MCPA6 in MCPA6/ABS blends were all decreased. The degree of supercooling (ΔTd) showed a contrary trend. However, the melting temperatures of these blends were almost unchanged. All the results could be attributed to in situ polymerization and the hydrolysis reaction of ABS that occurred during the polymerization process. Furthermore, WAXD results showed that only α‐form crystals existed in the MCPA6/ABS blends, despite the ABS content and heat treatment.

SEM micrograph of the fractured surface of an MCPA6/ABS blend with an ABS content of 20 wt.‐% (×10 000).

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SEM micrograph of the fractured surface of an MCPA6/ABS blend with an ABS content of 20 wt.‐% (×10 000).
Triggering the Thermosensitive Properties of Hydrophobically Modified Poly(N‐isopropylacrylamide) by Complexation with Cyclodextrin Polymers
Authors: Wintgens Véronique , Charles Michaël , Allouache Farid , Amiel Catherine
Published: September 2005

Summary: Hydrophobically modified poly(N‐isopropylacrylamide) (PNIPAM) containing either an adamantyl or a dodecyl group were prepared and characterized. Self‐association in aqueous solutions was evidenced by fluorescence measurements using pyrene as a probe. The lower critical solution temperatures (LCST) were determined from cloud point measurements. They strongly depended on the hydrophobic group and the substitution level. The association between hydrophobically modified PNIPAM and β‐cyclodextrin (monomers and polymers) was investigated by cloud point and viscosity measurements. The presence of β‐cyclodextrin monomers generally shifted the LCST to a higher temperature, the complexation increasing the solubility of PNIPAM chains. β‐Cyclodextrin polymers mixed with hydrophobically modified PNIPAM generated supramolecular assemblies. This was evidenced by viscosity measurements of the mixtures at temperatures lower than the LCST. Moreover, depending on the substitution level of the PNIPAM, the LCST was increased (1% hydrophobic groups) or decreased (4% hydrophobic groups) by more than 10 °C upon β‐cyclodextrin polymer addition.

Transmission variations of different mixtures of PNIPAM‐C12 with cyclodextrin compounds vs temperature.

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Transmission variations of different mixtures of PNIPAM‐C12 with cyclodextrin compounds vs temperature.
Rod‐Like Silicate‐Epoxy Nanocomposites
Authors: Lu Hongbin , Shen Hongbin , Song Zhenlun , Shing Katherine S. , Tao Wei , Nutt Steven
Published: September 2005

Summary: Epoxy nanocomposites containing rod‐like silicate (attapulgite) were prepared using a simple organic modification to the nanorods. The modification led to effective interfacial adhesion between the ceramic nanorods and the epoxy resin and hence good load transfer. Scanning electron microscopy examination revealed a uniform dispersion of nanorods in the epoxy resin. Compared to the neat resin, nanocomposites with 7.47 vol.‐% nanorods exhibited an increase in the (rubbery state) storage modulus of 122.5%. In addition, the nanocomposites exhibited improved dimensional stability both above and below the Tg.

Storage modulus of the neat resin and nanocomposites.

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Storage modulus of the neat resin and nanocomposites.
RAFT Polymerization of Pentafluorophenyl Methacrylate: Preparation of Reactive Linear Diblock Copolymers
Authors: Eberhardt Marc , Théato Patrick
Published: September 2005

Summary: Reversible addition fragmentation chain transfer (RAFT) polymerization of pentafluorophenyl methacrylate (PFMA) was carried out in the presence of cumyldithiobenzoate and 4‐cyano‐4‐((thiobenzoyl)sulfanyl)pentanoic acid, respectively. These chain transfer agents with 2,2′‐azoisobutyronitrile (AIBN) as initiator yielded the active ester polymer poly(PFMA) with $\overline M _{\rm n}$ up to 17 000 g · mol−1 and low polydispersity index ($\overline M _{\rm w} /\overline M _{\rm n}$ < 1.2). Kinetic analysis using 19F NMR spectroscopy and gel permeation chromatography (GPC) measurements showed controlled polymerization behavior for both chain transfer agents. Successful preparation of linear diblock copolymers consisting of an active ester block and methyl methacrylate, N‐acryloylmorpholine, or N,N‐diethylacrylamide, respectively, could be demonstrated. These polymers could easily react with amines in a polymer analogous reaction to form multifunctional polymers.

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Formation of o‐Phenylenediamine Oligomers and their Self‐Assembly into One‐Dimensional Structures in Aqueous Medium
Authors: Sun Xuping , Dong Shaojun , Wang Erkang
Published: September 2005

Summary: Uniform one‐dimensional (1D) structures of o‐phenylenediamine (oPD) oligomers are obtained by direct mix of AgNO3 and oPD aqueous solutions at room temperature. The formation of the 1D structures involves two stages: (1) oxidation of oPD by AgNO3, yielding individual oPD oligomers; and (2) self‐assembly of the oligomers, forming the 1D structures. Upon decreasing medium pH, the 1D structures can break‐apart to form individual oligomers, or vice versa. It is also found that both the concentration and molar ratio of reactants can influence the morphology of the structures thus formed.

Schematic illustration of the formation mechanism of 1D structures from oPD and AgNO3, and energy‐dispersed spectrum of the precipitate.

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Schematic illustration of the formation mechanism of 1D structures from oPD and AgNO3, and energy‐dispersed spectrum of the precipitate.
Genetic heterogeneity in patients with pantothenate kinase–associated neurodegeneration and classic magnetic resonance imaging eye‐of‐the‐tiger pattern
Authors: Valentino Paola , Annesi Grazia , Cirò Candiano Innocenza C. , Annesi Ferdinanda , Civitelli Donatella , Tarantino Patrizia , Naso Francesco , Spadafora Patrizia , Carrideo Sara , De Marco Elvira V. , Consoli Domenico , Zappia Mario , Gambardella Antonio , Quattrone Aldo
Published: September 2005

We performed a detailed molecular study in two unrelated families with pantothenate kinase–associated neurodegeneration (PKAN) and the specific magnetic resonance imaging (MRI) eye‐of‐the‐tiger pattern. In the first family with classic PKAN, linkage analysis using polymorphic markers from the PANK2 region ruled out linkage with this locus, and no mutation of the PANK2 gene was found. In the second family with atypical PKAN, we identified a novel homozygous C‐to‐T transition at nucleotide 1069 of the PANK2 gene, which resulted in an arginine to tryptophane substitution at codon 357. As far as we are aware, this is the first case of classic PKAN with the specific MRI eye‐of‐the‐tiger pattern not carrying a PANK2 mutation. Therefore, the present observation reinforces the notion of the phenotypic and genetic heterogeneity in PKAN. © 2005 Movement Disorder Society
Orthostatic tremor during modification of standing
Authors: Spiegel Jörg , Krick Christoph , Fuss Gerhard , Sood Dania , Becker Georg , Dillmann Ulrich
Published: September 2005

Primary orthostatic tremor (OT) occurs only during standing. We studied whether modification of the condition standing influences OT. In seven patients with OT, surface EMG was recorded from both tibialis anterior and gastrocnemius muscles during two maneuvers: relief, whereby the patient was gradually lifted by a crane, and tilting, whereby the patient was tilted by a tilting table to positions of 90° (upright standing), 45° (diagonal position), and 0° (lying position). We determined the parameters tremor frequency, tremor intensity, coherence, and phase shift between the different muscles. Relief did not influence OT. In contrast, tilting modified significantly tremor intensity and phase shifts; tremor frequencies and coherences were not influenced. We chose both these maneuvers because of their different impact on the standing condition: relief modifies the factors afferent input and muscle forcing but not the factor postural set, whereas tilting modifies all three factors. The fact that tilting modifies OT, whereas relief does not, suggests an important role of postural set in OT generation. Afferent input and muscle forcing seem to play less important role. © 2005 Movement Disorder Society
Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients
Authors: Dragašević Nataša T. , Čuljković Biljana , Klein Christine , Ristić Aleksandar , Keckarević Milica , Topisirović Ivan , Vukosavić Slobodanka , Svetel Marina , Kock Norman , Stefanova Elka , Romac Stanka , Kostić Vladimir S.
Published: September 2005

The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1–3, 6–8, 12, 17; dentate–rubro–pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult‐onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult‐onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia‐causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult‐onset ataxia. © 2005 Movement Disorder Society
Reply: Akinetic crisis, acute akinesia, neuroleptic malignant‐like syndrome, Parkinsonism–hyperpyrexia syndrome, and malignant syndrome are the same entity and are often independent of treatment withdrawal
Authors: Kipps Christopher M. , Fung Victor S.C. , Grattan‐Smith Padraic , deMoore Gregory M. , Morris John G.L.
Published: September 2005

The original letter to which this reply refers was published in Movement Disorders Mov Disord (2005)DOI 10.1002/mds.20689.
Akinetic crisis, acute akinesia, neuroleptic malignant‐like syndrome, Parkinsonism–hyperpyrexia syndrome, and malignant syndrome are the same entity and are often independent of treatment withdrawal
Authors: Thomas Astrid , Onofrj Marco
Published: September 2005

A reply to this letter has been published in Movement Disorders Mov Disord (2005)DOI 10.1002/mds.20688.
Magnetic stimulation using a triple‐stimulation technique in patients with multifocal neuropathy without conduction block
Authors: Attarian Shahram , Azulay Jean‐Philippe , Verschueren Annie , Pouget Jean
Published: September 2005

It has been suggested previously that multifocal motor neuropathy (MMN) without conduction block (CB) or other features of demyelination is axonal in nature. Conventional transcranial magnetic stimulation (TMS) and the triple‐stimulation technique (TST) performed on 10 MMN patients without CB revealed a proximal focal CB in 4 patients. In 3 other patients, the amplitude ratio obtained in response to conventional TMS was abnormally low, but the area ratio was normal. The TST amplitude ratio and area ratio were normal in these 3 patients. This pattern suggested the occurrence of temporal dispersion without CB. The occurrence of temporal dispersion or CB was associated with a relatively satisfactory response to intravenous immunoglobulins. These findings suggest that some forms of MMN previously thought to be axonal are in fact proximal variants of MMN with CB. Muscle Nerve, 2005
Conformational variation and crystalline phase transformation of low syndiotactic polypropylene films in stretched and stress‐relaxed states
Authors: Zhang Xiu‐Qin , Zhao Ying , Shi Hai‐Feng , Dong Xia , Wang Du‐Jin , Han Charles C. , Xu Duan‐Fu
Published: September 2005

Low syndiotactic polypropylene (sPP; rrrr = 80%) films were isothermally crystallized at 0 °C (sample S0) and 90 °C (sample S90) for 65 h, respectively. Fourier transform infrared spectroscopy, differential scanning calorimetry, and wide‐angle X‐ray diffraction were used to characterize the structure transformation and orientation behavior of samples S0 and S90 at both stretched and stress‐relaxed states. It was found that stretching (λ = 0–700%) induces the transformation of the chain conformation from helical to trans‐planar form for both S0 and S90 films. The stretched S0 and S90 samples show well oriented trans‐planar chains as well as partially retained helices. Simultaneously, crystalline phase transformation occurs during the stretching and relaxing processes of the investigated sPP samples, i.e., stable form I crystals can be transformed into metastable form III or mesophase by stretching samples, and vice versa. For stretched S0 sample, form III with trans‐planar conformation, which generally exists in highly stretched sPP, cannot be observed, even at higher strains. For sample S90, however, stretching might induce the formation of both the form III crystals and mesophase with trans‐planar chains; releasing the tension, form III again gets converted into trans‐planar mesophase and form I crystals. In the stretched and stress‐relaxed states of samples S0 and S90, the difference of the delicate orientation behavior and relative content of chain conformation and crystalline form can be attributed to the different heat‐treating methods of the low syndiotacticity sPP. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2924–2936, 2005
Phase separation behavior of aqueous solutions of a thermoresponsive polymer
Authors: Matsuda Yasuhiro , Miyazaki Yuji , Sugihara Shinji , Aoshima Sadahito , Saito Kazuya , Sato Takahiro
Published: September 2005

Cloud‐point and binodal curves of the LCST type were obtained for aqueous solutions of a thermoresponsive polymer, poly [2‐(2‐ethoxy)ethoxyethyl vinyl ether], poly(EOEOVE). The cloud‐point curve obtained was very flat except in a dilute region, that is the cloud‐point temperature was insensitive to the polymer concentration, resembling the cloud‐point curve for aqueous solutions of poly(N‐isopropylacrylamide). On the other hand, the binodal curve obtained was parabolic, and located within the two‐phase region of the cloud‐point curve. Accompanied with the phase separation, a sharp endothermic peak was observed in a region including the cloud‐point and binodal temperatures. The reciprocal of the osmotic compressibility ∂Π/∂c obtained by sedimentation equilibrium indicated that water changes from a good to poor solvent for poly(EOEOVE) with increasing temperature. Analyzing the ∂Π/∂c data by a thermodynamic perturbation theory, we determined the interchain interaction parameters, the hard‐core diameter d and the depth ε of the square‐well potential. Theoretical binodal and endothermic curves calculated by the perturbation theory using the estimated interaction parameters reproduced experimental ones semiquantitatively, but the theoretical binodal disagreed with the experimental flat cloud‐point curve. The disagreement at high concentrations was in the opposite direction to that expected from the sample polydispersity in the molecular weight. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2937–2949, 2005
Local deformation in photo‐crosslinked polymer blends monitored by Mach‐Zehnder interferometry
Authors: Inoue Kyosuke , Komatsu Satonori , Trinh Xuan‐Anh , Norisuye Tomohisa , Tran‐Cong‐Miyata Qui
Published: September 2005

Local deformation of a polymer mixture crosslinked by irradiation with ultraviolet light was in situ monitored by using a Mach‐Zehnder interferometer. In combination with the refractive index data obtained from independent measurements, the deformation in the nanometer scales of the crosslinked blends was calculated by using the difference in optical path length of the blend measured before and after irradiation. Upon varying the crosslink density of the blend by changing the light intensity, it was found that the local deformation well correlates with the crosslink density obtained from the reaction kinetics experiments. Furthermore, the strain relaxation of the blends was also monitored in situ and analyzed after irradiation over different time intervals. The results obtained in this study reveal the possibility of monitoring the nanometer‐scale deformation in polymers during radiation curing. These data also provide important information on the correlations between the irradiation‐induced elastic strain and the resulting morphology of reacting polymer blends. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2898–2913, 2005
Crystal structure of a purine/pyrimidine phosphoribosyltransferase‐related protein from Thermus thermophilus HB8
Authors: Rehse Peter H. , Tahirov Tahir H.
Published: September 2005

Adenine phosphoribosyltransferase (APRTase) is a widely distributed enzyme involved in the salvage of adenine to form an adenine nucleotide. We crystallized and determined the X‐ray crystallographic structure of a purine/pyrimidine phosphoribosyltransferase‐related protein from the thermophilic bacterium, Thermus thermophilus HB8. The crystal space group was C2 with unit cell dimensions of a = 167.42 Å, b = 61.41 Å, c = 102.39 Å, β = 94.0°. Initial phases were determined to 2.6 Å using the multiple wavelength anomalous dispersion method and selenomethionine substituted protein (Se‐MAD), and refined using a 1.9 Å “native” data set. The asymmetric unit contains two pairs of identical dimers, each related by noncrystallographic two‐fold symmetry. The fifth monomer forms a similar dimer across a crystallographic two‐fold axis. These dimers appear to be the biological unit with both monomers contributing to an unusual highly charged arginine‐rich bridge region separating the two active sites. Comparison with distantly related APRTases reveal similarities and differences of the active site. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Sequence and structural determinants of Cu, Zn superoxide dismutase aggregation
Authors: Khare Sagar D. , Wilcox Kyle C. , Gong Peng , Dokholyan Nikolay V.
Published: September 2005

Diverse point mutations in the enzyme Cu, Zn superoxide dismutase (SOD1) are linked to its aggregation in the familial form of the disease amyotrophic lateral sclerosis. The disease‐associated mutations are known to destabilize the protein, but the structural basis of the aggregation of the destabilized protein and the structure of aggregates are not well understood. Here, we investigate in silico the sequence and structural determinants of SOD1 aggregation: (1) We identify sequence fragments in SOD1 that have a high aggregation propensity, using only the sequence of SOD1, and (2) we perform molecular dynamics simulations of the SOD1 dimer folding and misfolding. In both cases, we identify identical regions of the protein as having high propensity to form intermolecular interactions. These regions correspond to the N‐ and C‐termini, and two crossover loops and two β‐strands in the Greek‐key native fold of SOD1. Our results suggest that the high aggregation propensity of mutant SOD1 may result from a synergy of two factors: the presence of highly amyloidogenic sequence fragments (“hot spots”), and the presence of these fragments in regions of the protein that are structurally most likely to form intermolecular contacts under destabilizing conditions. Therefore, we postulate that the balance between the self‐association of aggregation‐prone sequences and the specific structural context of these sequences in the native state determines the aggregation propensity of proteins. Proteins 2005. © 2005 Wiley‐Liss, Inc.
How do side chains orient globally in protein structures?
Authors: Yan Aimin , Jernigan Robert L.
Published: September 2005

An angle Ω is defined to serve as a metric for global side‐chain orientations, which reflects the orientation of the side chain relative to the radial vector from the center of the protein to an amino acid. The side‐chain orientations of buried residues exhibit characteristically different orientations than do exposed residues, in both monomeric and dimeric structures. Overall, buried side chains point mostly inward, whereas surface side chains tend to point outward from the surface. This difference in behavior also correlates well with the residue hydrophobicity; so a global side‐chain orientation can be viewed as a direct structural manifestation of hydrophobicity. When various solvent‐accessible layers are considered, the behavior is relatively continuous between centrally located and exposed residues. In the case of interfacial residues between subunits, there are statistically significant differences between exposed residues and interface residues for ALA, ARG, ASN, ASP, GLU, HIS, LYS, THR, VAL, MET, PRO, and overall the interface residues have an increased tendency to point inward. Presumably, these substantial differences in orientations of side chains may be a manifestation of hydrophobic forces. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Predicting protein secondary structure and solvent accessibility with an improved multiple linear regression method
Authors: Qin Sanbo , He Yun , Pan Xian‐Ming
Published: September 2005

We have improved the multiple linear regression (MLR) algorithm for protein secondary structure prediction by combining it with the evolutionary information provided by multiple sequence alignment of PSI‐BLAST. On the CB513 dataset, the three states average overall per‐residue accuracy, Q3, reached 76.4%, while segment overlap accuracy, SOV99, reached 73.2%, using a rigorous jackknife procedure and the strictest reduction of eight states DSSP definition to three states. This represents an improvement of approximately 5% on overall per‐residue accuracy compared with previous work. The relative solvent accessibility prediction also benefited from this combination of methods. The system achieved 77.7% average jackknifed accuracy for two states prediction based on a 25% relative solvent accessibility mode, with a Mathews' correlation coefficient of 0.548. The improved MLR secondary structure and relative solvent accessibility prediction server is available at http://spg.biosci.tsinghua.edu.cn/. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Adhesion mechanism of salmon to polymer‐coated can walls
Authors: Dommershuijzen Hans , Hviid Lene , den Hartog Hans , Vereijken Johan
Published: September 2005

Minimization of the amount of salmon adhering to the can wall after emptying is one of the convenience requirements of consumers of canned salmon. In order to achieve this, the mechanism by which salmon adheres to cans needs to be understood. The aim of this study was to provide such knowledge for polymer‐coated cans. The results indicate that gelatin, derived from salmon collagen, and myofibrillar proteins are the major proteins involved in sticking of salmon to the polymer‐coated can wall. Furthermore, it was shown that mainly hydrogen bonds are formed between the salmon proteins and the polymer surface. Therefore, making the surface more apolar can prevent sticking of salmon to polymer‐coated cans. Copyright © 2005 John Wiley & Sons, Ltd.
Identifiability, stratification and minimum variance estimation of causal effects
Authors: Tong Xingwei , Zheng Zhongguo , Geng Zhi
Published: September 2005

The weakest sufficient condition for the identifiability of causal effects is the weakly ignorable treatment assignment, which implies that potential responses are independent of treatment assignment in each fine subpopulation stratified by a covariate. In this paper, we expand the independence that holds in fine subpopulations to the case that the independence may also hold in several coarse subpopulations, each of which consists of several fine subpopulations and may have overlaps with other coarse subpopulations. We first show that the identifiability of causal effects occurs if and only if the coarse subpopulations partition the whole population. We then propose a principle, called minimum variance principle, which says that the estimator possessing the minimum variance is preferred, in dealing with the stratification and the estimation of the causal effects. The simulation results with the detail programming and a practical example demonstrate that it is a feasible and reasonable way to achieve our goals. Copyright © 2005 John Wiley & Sons, Ltd.
Repeated split sample validation to assess logistic regression and recursive partitioning: an application to the prediction of cognitive impairment
Authors: James Kenneth E. , White Roberta F. , Kraemer Helena C.
Published: September 2005

Screening strategies play an important part in the identification and diagnosis of illness. Testing of such strategies in a clinical trial can have important implications for the treatment of such illnesses. Before the clinical trial, however, it is important to develop a practical screening/classification procedure that accurately predicts the presence of the illness in question. Recent published studies have shown a growing preference for classification tree/recursive partitioning procedures.

This paper compares the application of logistic regression and recursive partitioning to a neuropsychological data set of 252 patients recruited from four Veterans Affairs Medical Centers. Logistic regression and recursive partitioning was used to predict cognitive impairment in 12 randomly selected exploratory/validation samples. We assessed the effect of sampling on variable selection and predictive accuracy.

Predictive accuracy of the logistic regression and recursive partitioning procedures was comparable across the exploratory data samples but varied across the validation samples. Based on shrinkage, both classification procedures performed equally well for the prediction of cognitive impairment across the twelve samples. While logistic regression provided an estimated probability of outcome for each patient, it required several mathematical calculations to do so. However, logistic regression selected one or two less predictors than recursive partitioning with comparable predictive accuracy. Recursive partitioning, on the other hand, readily identified patient characteristics and variable interactions, was easy to interpret clinically and required no mathematical calculations. There was a high degree of overlap of the predictor variables between the two procedures.

In the context of neuropsychological screening, logistic regression and recursive partitioning performed equally well and were quite stable in the selection of predictors for the identification of patients with cognitive impairment, although recursive partitioning may be easier to use in a clinical setting because it is based on a simple decision tree. Copyright © 2005 John Wiley & Sons, Ltd.