bluuebunny/crossref_metadata_2025 huggingface dataset:
PRKX, TTBK2 and RSK4 expression causes sunitinib resistance in kidney carcinoma‐ and melanoma‐cell lines
Authors: Bender Claus , Ullrich Axel
Published: October 2011

Resistance to chemotherapeutic agents constitutes a major problem in the treatment of cancer. Over the past years, multi‐targeted protein kinase inhibitors such as Gleevec, Sunitinib and Sorafenib are gaining wider acceptance for cancer treatment. These drugs show anti‐tumor activity in vitro and in patients. Extended usage of these drugs in therapy commonly results in disease progression due to formation of resistance caused by rearrangements and accumulation of mutations in the unstable cancer cell genome. However, the underlying drug‐specific mechanisms for the development of resistance remain elusive. Hence, a detailed understanding of the molecular genetic events involved in this processes is pivotal to counteract are not directly targeted by Sunitinib (unpublished data). Therefore, development of specific or multi‐targeted inhibitors for these kinases for combinatorial therapy with e.g., an IL‐8 neutralizing antibody might circumvent or substantially delay Sunitinib resistance formation and enhance survival prognosis. PRKX, TTBK2 and RSK4 expression. The specific reduction of these genes employing siRNA was sufficient to sensitize the kidney‐ and melanoma‐cell lines against Sunitinib. In line with the elevated expression of PRKX, TTBK2 or RSK4, this sensitization effect was strikingly higher in the Sunitinib resistant cell lines, suggesting an expression‐based mechanism of these genes to trigger Sunitinib resistance. Hence, we propose that PRKX, TTBK2 and RSK4 are potential resistance markers in Sunitinib therapy and might therefore represent targets for the development of novel strategies to overcome resistance.
Chromosomal profiles of high‐grade cervical intraepithelial neoplasia relate to duration of preceding high‐risk human papillomavirus infection
Authors: Bierkens Mariska , Wilting Saskia M. , van Wieringen Wessel N. , van Kemenade Folkert J. , Bleeker Maaike C.G. , Jordanova Ekaterina S. , Bekker‐Lettink Marjolein , van de Wiel Mark A. , Ylstra Bauke , Meijer Chris J.L.M. , Snijders Peter J.F. , Steenbergen Renske D.M.
Published: October 2011

High‐grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5‐year history of high‐risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3‐SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3‐SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short‐term risk of cervical cancer.
Neuroblastoma triggers an immunoevasive program involving galectin‐1‐dependent modulation of T cell and dendritic cell compartments
Authors: Soldati Rocio , Berger Elisa , Zenclussen Ana C. , Jorch Gerhard , Lode Holger N. , Salatino Mariana , Rabinovich Gabriel A. , Fest Stefan
Published: October 2011

The immunosuppressive strategies devised by neuroblastoma (NB), the most common solid extracranial childhood cancer, are poorly understood. Here, we identified an immunoevasive program triggered by NB through secretion of galectin‐1 (Gal‐1), a multifunctional glycan‐binding protein. Human and mouse NB cells express and secrete Gal‐1, which negatively regulates T cell and dendritic cell function. When injected subcutaneously in syngeneic A/J mice, knockdown transfectants expressing low amounts of Gal‐1 (NXS2/L) showed reduction of primary tumor growth by 83–90% and prevented spontaneous liver metastases in contrast to NXS2 cell variants (NXS2/H, NXS2 wildtype) expressing high amounts of Gal‐1. Splenocytes from mice receiving Gal‐1 knockdown NXS2/L cells secreted higher amounts of IFN‐γ and displayed enhanced cytotoxic T‐cell function compared to NXS2/H or NXS2 controls. Immunohistochemical analysis revealed a six‐ to tenfold increase in the frequency of CD4+ and CD8+ T cells infiltrating tumors from mice receiving knockdown transfectants. This effect was confirmed by in vitro migration assays. Finally, supernatants of NXS2/H or NXS2 cells suppressed dendritic cell (DC) maturation and induce T cell apoptosis, whereas these effects were only marginal on DCs and T cells exposed to supernatants from NXS2/L cells. These results demonstrate a novel immunoinhibitory role of the Gal‐1‐glycan axis in NB, highlighting an alternative target for novel immunotherapeutic modalities.
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations
Authors: Mulholland Shani , Pearson Danita M. , Hamoudi Rifat A. , Malley Deborah S. , Smith Caroline M. , Weaver Jamie M.J. , Jones David T.W. , Kocialkowski Sylvia , Bäcklund L. Magnus , Collins V. Peter , Ichimura Koichi
Published: October 2011

We have previously identified a region containing 16 CpGs within the MGMT CpG islands which is critical for the transcriptional control of MGMT (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of MGMT methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The MGMT gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low MGMT expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of MGMT methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with IDH1/IDH2 mutations except two had MGMT methylation, while there were many tumors with MGMT methylation, particularly primary glioblastomas, which had no mutations of IDH1/2. We suggest that MGMT methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.
Characteristics and survival of head and neck cancer by HPV status: a cancer registry‐based study
Authors: Sethi Seema , Ali‐Fehmi Rouba , Franceschi Silvia , Struijk Linda , van Doorn Leen‐Jan , Quint Wim , Albashiti Bassam , Ibrahim Majd , Kato Ikuko
Published: October 2011

Elucidation of the role of human papillomavirus (HPV) in the etiology and prognosis of squamous carcinomas of the head and neck (HNSCC) is essential to optimize prevention and treatment strategies for this disease. We analyzed 385 HNSCC tissue blocks identified through a population‐based cancer registry in Metropolitan Detroit for HPV DNA using a broad‐spectrum PCR technique (SPF10‐LiPA25) to correlate with patient and tumor characteristics and overall survival. Overall, HPV DNA (any type) was detected in 29.4% of all HNSCC, but it was significantly more prevalent (50.6%) in oropharyngeal sites (N = 81), where 90% of HPV were type 16, than in other sites. HPV prevalence (any type) in oropharyngeal sites was highest in patients with a negative smoking indicator, Caucasians and in regional tumor stage. Likewise, only in oropharyngeal sites did patients overall positive to HPV show significantly better survival compared with HPV‐negative patients, notably among those who had been irradiated. The best and the worst survival from cancer in oropharyngeal sites were found, respectively, among HPV‐positive patients with negative smoking indicator and among HPV‐negative patients with positive smoking indicator. The results of this study revealed that the presence of HPV DNA was associated with patients' specific characteristics and better overall survival exclusively in oropharyngeal sites. To define the fraction of HNSCC preventable by HPV vaccination or amenable to less aggressive treatment, however, tobacco exposure and HPV markers other than DNA presence need to be taken into account.
The JmjC domain‐containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene
Authors: Cho Hyun‐Soo , Toyokawa Gouji , Daigo Yataro , Hayami Shinya , Masuda Ken , Ikawa Noriko , Yamane Yuka , Maejima Kazuhiro , Tsunoda Tatsuhiko , Field Helen I. , Kelly John D. , Neal David E. , Ponder Bruce A.J. , Maehara Yoshihiko , Nakamura Yusuke , Hamamoto Ryuji
Published: October 2011

A number of histone demethylases have been identified and biochemically characterized, yet their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. In this study, we describe important roles for the histone demethylase KDM3A, also known as JMJD1A, in human carcinogensis. Expression levels of KDM3A were significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (p < 0.0001), when assessed by real‐time PCR. We confirmed that some other cancers including lung cancer also overexpressed KDM3A, using cDNA microarray analysis. Treatment of cancer cell lines with small interfering RNA targeting KDM3A significantly knocked down its expression and resulted in the suppression of proliferation. Importantly, we found that KDM3A activates transcription of the HOXA1 gene through demethylating histone H3 at lysine 9 di‐methylation by binding to its promoter region. Indeed, expression levels of KDM3A and HOXA1 in several types of cancer cell lines and bladder cancer samples were statistically correlated. We observed the down‐regulation of HOXA1 as well as CCND1 after treatment with KDM3A siRNA, indicating G1 arrest of cancer cells. Together, our results suggest that elevated expression of KDM3A plays a critical role in the growth of cancer cells, and further studies may reveal a cancer therapeutic potential in KDM3A inhibition.
Lack of CCR7 expression is rate limiting for lymphatic spread of pancreatic ductal adenocarcinoma
Authors: Sperveslage Jan , Frank Sunna , Heneweer Carola , Egberts Jan , Schniewind Bodo , Buchholz Malte , Bergmann Frank , Giese Nathalia , Munding Johanna , Hahn Stephan A. , Kalthoff Holger , Klöppel Günter , Sipos Bence
Published: October 2011

CCR7 expression on tumor cells promotes lymphatic spread in several malignant tumors. However, a comprehensive characterization of the CCL19/CCL21–CCR7 axis in pancreatic ductal adenocarcinoma (PDAC), which is known for its high rates of lymph‐node metastases, is still lacking. CCR7 mRNA and CCR7 protein were found to be expressed in spheroid cultures of all six examined PDAC cell lines. In migration assays, CCR7 expressing PDAC cells showed enhanced migration toward CCL19 and CCL21, the two ligands of CCR7. In an orthotopic nude mouse model, CCR7‐transfected PT45P1 cells gave rise to significantly larger tumors and showed a higher frequency of lymph vessel invasion and lymph‐node metastases than mock‐transfected cells. In an analysis using quantitative real‐time PCR, CCR7 showed fourfold overexpression in microdissected PDAC cells compared to normal duct cells. Moderate‐to‐strong immunohistochemical CCR7 expression, found in 58 of 121 well‐characterized human PDACs, correlated with high rates of lymph vessel invasion. Conversely, PDACs completely lacking CCR7 expression showed only low rates of lymph vessel invasion and lymph‐node metastases. The evaluation of CCL21 expression by immunofluorescence staining revealed a significant upregulation of CCL21 in peritumoral and intratumoral lymph vessels compared to lymph vessels in disease‐free pancreata. In conclusion, our study revealed strong evidence that lack of CCR7 impairs the metastatic potential of PDAC. Lymph vessel invasion by CCR7 expressing PDAC cells may be additionally enhanced by upregulation of CCL21 in tumor‐associated lymph vessels, representing a previously unknown factor of lymphatic spread.
CD99 triggers upregulation of miR‐9‐modulated PRDM1/BLIMP1 in Hodgkin/Reed–Sternberg cells and induces redifferentiation
Authors: Huang Xueping , Zhou Xinhua , Wang Zhiqiang , Li Feng , Liu Fanrong , Zhong Lin , Li Xiangzhao , Han Xiqun , Wu Ziqing , Chen Shaohong , Zhao Tong
Published: October 2011

CD99 is a 32‐kDa transmembrane glycoprotein that is encoded by the MIC2 gene. Our study was carried out to examine the role of CD99 in tumor progression of classical Hodgkin lymphoma (cHL). Here, we showed that lowly expressed CD99 protein in cHL cell lines and primary cHL cases correlates with the deficient expression of the positive regulatory domain 1 (PRDM1/BLIMP1). In addition, cHL cell lines showed high levels of miR‐9 expression. We determined that the upregulation of CD99 induced expression of transcription factor PRDM1, a master regulator of plasma‐cell differentiation, which is also a target for miR‐9‐mediated downregulation. Indeed, inhibition of miR‐9 also triggered upregulation of PRDM1 expression. Furthermore, overexpression of CD99 resulted in changed growth features and reorganization of actin cytoskeleton. As upregulation of CD99 led to a decrease in cHL diagnosis marker CD30 and CD15 and an increase in plasma‐cell differentiation marker CD38 and the restoration of B‐cell makers PAX5, CD79α and CD19, we suggest that downregulated CD99 leads to the prevention of plasma‐cell differentiation in Hodgkin/Reed–Sternberg (H/RS) cells. Furthermore, these data indicate that CD99 may control miR‐9 expression, which directly targets PRDM1. Altogether, these results reveal a CD99‐miR‐9‐PRDM1 molecule axis in lymphomagenesis of cHL and suggest that upregulation of CD99 in H/RS cells induces terminal B‐cell differentiation, which may provide a novel therapeutic strategies for cHL.
Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: Reduction post‐bortezomib monotherapy
Authors: Terpos Evangelos , Christoulas Dimitrios , Katodritou Eirini , Bratengeier Cornelia , Gkotzamanidou Maria , Michalis Eurydiki , Delimpasi Sosana , Pouli Anastasia , Meletis John , Kastritis Efstathios , Zervas Konstantinos , Dimopoulos Meletios A.
Published: November 2011

Sclerostin is a Wingless and Int‐1 inhibitor, which is produced by osteocytes and inhibits osteoblast‐driven bone formation. Sclerostin is implicated in the pathogenesis of bone loss in metabolic bone disorders but there is no information for its effect on multiple myeloma (MM)‐related osteolytic disease. We evaluated circulating sclerostin in 157 newly diagnosed patients with symptomatic myeloma, in 25 with relapsed myeloma who received bortezomib monotherapy, in 21 patients with monoclonal gammopathy of undetermined significance (MGUS), and in 21 healthy controls. Patients with active myeloma had elevated circulating sclerostin compared to MGUS patients and controls (p < 0.01). MM patients who presented with fractures at diagnosis (n = 34) had very high levels of circulating sclerostin compared with all others (p < 0.01), whereas sclerostin correlated negatively with bone specific alkaline phosphatase (a bone formation marker; r = −0.541, p < 0.0001) and positively with C‐telopeptide of collagen type‐1 (a bone resorption marker; r = 0.524, p < 0.0001). Patients with International Staging System (ISS)‐3 disease had higher circulating sclerostin compared to ISS‐1 and ISS‐2 MM (p = 0.001). Furthermore, patients with high sclerostin (upper quartile, n = 40) had a median survival of 27 months versus 98 months of all others (p = 0.031). Relapsed MM patients had higher levels of circulating sclerostin even compared to newly diagnosed patients (p < 0.01). Bortezomib monotherapy resulted in a reduction of sclerostin by almost 50% in both responders and non‐responders. These results suggest that patients with active myeloma have elevated circulating sclerostin, which correlated with advanced disease features including severe bone disease. Our study indicates sclerostin as a possible target for the development of novel therapies to enhance osteoblast function in myeloma.
Bisphenol A decreases atrial contractility involving NO‐dependent G‐cyclase signaling pathway
Authors: Pant Jayanti , Ranjan Pratibha , Deshpande Shripad B.
Published: October 2011

Bisphenol A (BPA) is used in manufacturing plastics. Even though BPA is reported to produce reproductive and behavioral toxicity in experimental animals, the direct effect of BPA on the cardiovascular system is not known. The present study was therefore undertaken to evaluate the effect of BPA, on spontaneously beating rat right atrial preparations. In this study, in vitro isometric contractions of right atria were recorded. Cumulative concentration–response of BPA on atrial contractions was obtained in the absence or presence of antagonists. BPA (0.1–100 μ m) decreased the rate and the force of atrial contractions in a concentration‐dependent manner. At 100 μ m, the decreases were >90%. The BPA‐induced changes were not blocked by atropine (muscarinic receptor blocker). However, pretreatment with N‐ω‐nitro‐ l‐arginine methyl ester ( l‐NAME, a nitric oxide synthase inhibitor) or methylene blue (a guanylyl cyclase inhibitor) blocked the BPA‐induced changes in rate and force. Nitroglycerine, an NO‐donor, decreased the rate and force of atrial contractions. Further, the BPA‐induced changes were not due to the solvent (ethanol) used to dissolve it. The present study therefore indicates that BPA decreases the atrial contractility involving NO‐dependent G‐cyclase signaling mechanisms.
Repair of articular cartilage defects with a novel injectablein situforming material in a canine model
Authors: Igarashi Tatsuya , Iwasaki Norimasa , Kawamura Daisuke , Kasahara Yasuhiko , Tsukuda Yukinori , Ohzawa Nobuo , Ito Masayuki , Izumisawa Yasuharu , Minami Akio
Published: October 2011

We developed an ultra‐purifiedin situforming gel as an injectable delivery vehicle of bone marrow stromal cells (BMSCs). Our objective was to assess reparative tissues treated with autologous BMSCs implanted using the injectable implantation system into osteochondral defects in a canine model. Forty‐eight osteochondral defects in the patella groove of the knee joint were created in 12 adult beagle dogs (two defects in each knee). The defects were divided into a defect group (n= 16), an acellular novel material implantation (material) group (n= 16), and a BMSCs implantation using the current vehicle system (material with BMSCs) group (n= 16). The reparative tissues at 16 weeks postoperatively were assessed through gross, histological, and mechanical analyses. The reparative tissues of the material with BMSCs group were substituted with firm and smooth hyaline‐like cartilage tissue that was perfectly integrated into the host tissues. This treatment group obviously enhanced the subchondral bone reconstruction. The compressive modulus of the reparative tissues was significantly higher in the material with BMSCs group than the other groups. This study demonstrated that the implantation of BMSCs using our novelin situforming material induced a mature hyaline‐like cartilage repair of osteochondral defects in a canine model. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
The effect of adding an equine bone matrix protein lyophilisate on fixation and osseointegration of HA‐coated Ti implants
Authors: Baas Jorgen , Jakobsen Thomas , Elmengaard Brian , Bechtold Joan E. , Soballe Kjeld
Published: October 2011

Joint replacements should be firmly anchored in vital bone to avoid early implant subsidence and late aseptic loosening. We investigated whether the fixation of orthopedic implants could be improved by adding an osteoinductive extract of lyophilized equine bone matrix proteins (Colloss E, Ossacur AG, Germany), between the implant and the surrounding bone. Eighteen uncemented HA‐coated implants were inserted pairwise in the proximal tibia of nine dogs. All implants were surrounded by a 2 mm concentric defect. In each dog, the intervention implant was added 20 mg protein lyophilisate. The contralateral control implant was inserted untreated. After four weeks, the treated HA‐coated implants had better mechanical fixation than the untreated control implants. The treated implants were better osseointegrated, there was more newly formed bone around these implants, and fibrous tissue was eliminated. The mechanical implant fixation had a strong positive correlation to new bone formation on and around the implant, and a strong negative correlation to fibrous tissue encapsulation. The results suggest that bone protein extracts such as the Colloss E device may augment early implant fixation of even HA‐coated Ti implants and thereby reduce the risk of long‐term failure. This may be particularly useful in revision arthroplasty with bone loss. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Design and mechanical evaluation of a novel fiber‐reinforced scaffold for meniscus replacement
Authors: Balint Eric , Gatt Charles J. , Dunn Michael G.
Published: October 2011

A fiber‐reinforced degradable scaffold for replacement of meniscal tissue was designed, fabricated, and mechanically evaluated. The hypotheses were that (1) the fiber network design would share a portion of compressive loads via the generation of circumferential tensile loads, and (2) the scaffold tensile properties would be similar to those of the meniscus. Two meniscus scaffold designs varying in fiber content (1000 or 500 fibers: MS1000, MS500) underwent cyclic compressive loading up to 100 and 250N, with resultant tensile loads measured at the anterior and posterior anchors. Standard tensile testing was also performed on each device and ovine menisci. Both scaffolds generated tensile loads directly proportional to the applied compressive loads, with MS1000 scaffolds generating approximately twice the tensile loads of MS500 scaffolds. The tensile strength of MS1000 scaffolds was significantly higher than that of the medial and lateral ovine menisci, and approximately twice that of the MS500 scaffolds. The stiffness of MS1000 scaffolds was lower than that of the lateral meniscus, but not statistically different from that of the medial meniscus. These results support our hypotheses that this novel fiber‐reinforced scaffold can mimic the tensile and hoop stress behavior of normal meniscal tissue under compressive loading. The circumferential tensile strength and stiffness are appropriate for a meniscus replacement device. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Paclitaxel‐loaded silk fibroin nanospheres
Authors: Chen Mengjie , Shao Zhengzhong , Chen Xin
Published: October 2011

Silk fibroin is a very promising biomedical material because of its renewability, nontoxicity, biocompatibility, and biodegradability. On the basis of a simple and mild method for the preparation of silk fibroin nanospheres with controllable size, the authors developed earlier, anti‐cancer drug paclitaxel (PTX)‐loaded silk fibroin nanospheres ranging from 270 to 520 nm were produced accordingly. The drug loading, encapsulation efficiency, and released property of PTX‐loaded silk fibroin nanospheres are depended on the silk fibroin concentration and initial PTX‐loading capacity. The maximum drug loading is about 6.9% and the release time of such a kind of nanospheres is over 9 days. The release time of PTX‐loaded silk fibroin nanospheres can be as long as 2 weeks when the drug loading is about 3.0%. All these results imply that such a kind of biomacromolecule‐based anti‐cancer drug nanocarrier has a great potential for chemotherapy in clinical applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
LOCKING‐IN CARBON, LOCKING‐OUT LIVELIHOODS? ARTISANAL MINING AND REDD IN SUB‐SAHARAN AFRICA
Authors: Hirons Mark
Published: October 2011

This article examines the potential mutual conflict between interventions aimed at formalising artisanal and small‐scale mining (ASM) on the one hand, and policies implemented in response to the Reducing Emissions from Deforestation and Forest Degradation (REDD) initiative on the other. Deforestation caused by ASM undermines sound forest management, and potentially threatens the implementation of REDD. Conversely, the adoption of REDD could further marginalise and criminalise the ASM sector, reducing its contribution to poverty alleviation. Reviewing a series of commonalities between ASM and forest management highlights many difficulties facing policy‐makers. Potentially, contradictory outcomes of evolving governance arrangements means novel cross‐sectoral institutions will be required to realise the full potential of REDD and ASM to address poverty reduction in a complementary fashion. The analysis reiterates the centrality of livelihoods to REDD and the need for policies to take into account local contexts. Copyright © 2011 John Wiley & Sons, Ltd.
Sperm storage by spermatodoses in the spermatheca of Trioza alacris (Flor, 1861) hemiptera, psylloidea, triozidae: A structural and ultrastructural study
Authors: Marchini Daniela , Del Bene Giovanna , Viscuso Renata , Dallai Romano
Published: October 2011

Female insects generally store sperm received during mating in specific organs of their reproductive tract, i.e., the spermathecae, which keep the sperm alive for a long time until fertilization occurs. We investigated spermatheca morphology and ultrastructure in the psylloidean insect Trioza alacris (Flor,1861) in which spheroidal sperm packets that we refer to as ‘spermatodoses’ are found after mating. The ectoderm‐derived epithelium of the sac‐shaped spermatheca that has a proximal neck, consists of large secretory and flat cuticle‐forming cells. Secretory cells are characterized by a wide extracellular cavity, bordered by microvilli, in which electron‐dense secretion accumulates before discharge into the spermathecal lumen. The cuticle‐forming cells produce the cuticular intima of the organ and a peculiar specialized apical structure, through which secretion flows into the lumen. At mating, the male transfers bundles of sperm cells embedded in seminal fluid into the spermathecal neck. Sperm cells proceed towards the spermathecal sac lumen, where they are progressively compacted and surrounded with an envelope that also encloses secretions of both male and female origin. We describe the formation of these sperm containing structures and document the contribution of the female secretion to spermatodose or female‐determined spermatophore construction. We also discuss the choice of the term ‘spermatodose’ for T. alacris and suggest it be used to refer to sperm masses constructed in the female reproductive organs, at least when they involve the contribution of female secretion. © 2011 Wiley Periodicals, Inc.
Observations on the anterior testicular ducts in snakes with emphasis on sea snakes and ultrastructure in the yellow‐bellied sea snake, Pelamis platurus
Authors: Sever David M. , Freeborn Layla R.
Published: October 2011

The anterior testicular ducts of squamates transport sperm from the seminiferous tubules to the ductus deferens. These ducts consist of the rete testis, ductuli efferentes, and ductus epididymis. Many histological and a few ultrastructural studies of the squamate reproductive tract exist, but none concern the Hydrophiidae, the sea snakes and sea kraits. In this study, we describe the anterior testicular ducts of six species of hydrophiid snakes as well as representatives from the Elapidae, Homolapsidae, Leptotyphlopidae, and Uropeltidae. In addition, we examine the ultrastructure of these ducts in the yellow‐bellied Sea Snake, Pelamis platurus, only the third such study on snakes. The anterior testicular ducts are similar in histology in all species examined. The rete testis is simple squamous or cuboidal epithelium and transports sperm from the seminiferous tubules to the ductuli efferentes in the extratesticular epididymal sheath. The ductuli efferentes are branched, convoluted tubules composed of simple cuboidal, ciliated epithelium, and many species possess periodic acid‐Schiff+ granules in the cytoplasm. The ductus epididymis at the light microscopy level appears composed of pseudostratified columnar epithelium. At the ultrastructural level, the rete testis and ductuli efferentes of P. platurus possess numerous small coated vesicles and lack secretory vacuoles. Apocrine blebs in the ductuli efferentes, however, indicate secretory activity, possibly by a constitutive pathway. Ultrastructure reveals three types of cells in the ductus epididymis of P. platurus: columnar principal cells, squamous basal cells, and mitochondria‐rich apical cells. This is the first report of apical cells in a snake. In addition, occasional principal cells possess a single cilium, which has not been reported in reptiles previously but is known in some birds. Finally, the ductus epididymis of P. platurus differs from other snakes that have been studied in possession of apical, biphasic secretory vacuoles. All of the proximal ducts are characterized by widening of adjacent plasma membranes into wide intercellular spaces, especially between the principal cells of the ductus epididymis. Our results contribute to a larger, collaborative study of the evolution of the squamate reproductive tract and to the potential for utilizing cellular characters in future phylogenetic inferences. J. Morphol. 2012. © 2011 Wiley Periodicals, Inc.
CD34 and SMA expression of superficial zone cells in the normal and pathological human meniscus
Authors: Declercq Heidi A. , Forsyth Ramses G. , Verbruggen August , Verdonk René , Cornelissen Maria J. , Verdonk Peter C.M.
Published: October 2011

The aim of this study was to evaluate histological changes in torn (0.5–27 weeks after injury) and osteoarthritic (OA) knee menisci versus normal menisci after PAS‐AB, SAF‐O‐FG, and immunostaining for CD34, CD31, and smooth muscle actin (SMA). Cell layers in the superficial zone and the cell density in the deep zone of the menisci were counted. In the superficial zone of normal menisci, cells expressing CD34 were demonstrated. CD34+ CD31− cells were absent in OA menisci and disappeared in torn menisci as a function of time. In contrast, an increase of SMA+ cells combined with an increase of cell layers was observed in the superficial zone of torn menisci. SMA+ cells were absent in normal and OA menisci. The predominant tissue type in torn menisci evolved from fibrocartilage‐like to fibrous‐like tissue as a function of time, whereas in OA menisci it became cartilage‐like. The response of the superficial zone was reflected by the decrease of CD34+ and the increase of SMA+ cells in torn menisci and the transformation of a fibrous‐like into a cartilage‐like surface layer in OA menisci. These results potentially illustrate the contribution of CD34+ cells to the homeostasis of meniscus tissue. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:800–808, 2012
Atypical fibroxanthoma: Clinicopathologic determinants for recurrence and implications for surgical management
Authors: Davidson John S. , Demsey Daniel
Published: October 2011

Background and Objectives

Atypical fibroxanthoma (AFX) is an uncommon skin tumor occurring primarily in the head and neck region of elderly Caucasian males. Treated with local excision, the disease is thought to be fairly benign but can occasionally demonstrate aggressive local recurrence as well as distant metastasis.

Methods

Seventy‐one cases of AFX were reviewed, representing all patients presenting to the Health Sciences Centre of South Eastern Ontario with the diagnosis of AFX in the period 1989–2008. Demographic and pathologic data were obtained from patient charts for analysis.

Results

Mean age at presentation was 76, with a male:female ratio of 4:1. Recurrence occurred in 10 patients after an average period of 7.3 months. Three recurrent lesions went on to distant metastasis, on average 14.3 months after initial presentation. The remaining 60 tumors did not recur. Histologically, tumor extending beyond the dermis into the underlying adipose and muscular tissue had a 29.4% chance of local recurrence and an 11.8% chance of metastasis compared to lesions confined to the dermis only (9.3% and 1.8%).

Conclusions

While the majority of AFX presentations are benign, there is a real possibility of metastatic spread. Invasion beyond the dermis and a rapid rate of recurrence are suggestive of a more aggressive clinical course. J. Surg. Oncol. 2012; 105:559–562. © 2011 Wiley Periodicals, Inc.
DIVERSITY AND DYNAMICS OF MANAGEMENT OF GUM AND RESIN RESOURCES IN ETHIOPIA: A TRADE‐OFF BETWEEN DOMESTICATION AND DEGRADATION
Authors: Lemenih M. , Wiersum K. F. , Woldeamanuel T. , Bongers F.
Published: October 2011

Although the human domestication of forest and tree resources is often considered to result in resource degradation, it may also lead to improved resource potentials. This paper assesses the nature and dynamics of gum and resin focused woodland exploitation and management systems in Ethiopia in the context of degradation and domestication processes. In three sites with commercial gum resin producing woodlands and production history, we studied variation in (i) woodland management and gum resin production systems and (ii) socio‐economic and biophysical factors that condition the management and production systems. On the basis of their organizational features, we formulated nine production models and related them to different phases of domestication and different degrees of ecosystem degradation. The production systems gradually evolved from the extraction of wild trees to production in an adapted forest system. However, domesticated woodlands with an adapted forest structure and composition and increased provisioning services are still little developed despite decades of production history. Many of these woodlands are undergoing serious degradation because of low quality management practices. This is mainly attributable to existing land use practices and the social arrangements for the production of and trade in the gums and resins. The findings illustrate that domestication involves not only a change in ecological and production systems but also the development of social arrangements for production and trade. We conclude that the status of domestication in a social sense determines whether forests and/or specific forest resources are degraded or aggraded in the sense of resource enrichment. Copyright © 2011 John Wiley & Sons, Ltd.
Cladosporol a stimulates G1‐phase arrest of the cell cycle by up‐regulation of p21waf1/cip1 expression in human colon carcinoma HT‐29 cells
Authors: Zurlo Diana , Leone Cinzia , Assante Gemma , Salzano Salvatore , Renzone Giovanni , Scaloni Andrea , Foresta Caterina , Colantuoni Vittorio , Lupo Angelo
Published: October 2011

Cladosporols, purified and characterized as secondary metabolites from Cladosporium tenuissimum, display an antifungal activity. In this study, we tested the antiproliferative properties of cladosporol A, the main isoform of this metabolite family, against human cancer cell lines. By assessing cell viability, we found that cladosporol A inhibits the growth of various human colon cancers derived cell lines (HT‐29, SW480, and CaCo‐2) in a time‐ and concentration‐dependent manner, specifically of HT‐29 cells. The reduced cell proliferation was due to a G1‐phase arrest, as assessed by fluorescence activated cell sorting analysis on synchronized HT‐29 cells, and was associated with an early and robust over‐expression of p21waf1/cip1, the well‐known cyclin‐dependent kinases inhibitor. This suggests that the drug may play a role in the control of cancer cell proliferation. Consistently, cyclin D1, cyclin E, CDK2, and CDK4 proteins were reduced and histone H1‐associated CDK2 kinase activity inhibited. In addition to p21waf1/cip1, exposure to 20 µM cladosporol A caused a simultaneous increase of pERK and pJNK, suggesting that this drug activates a circuit that integrates cell cycle regulation and the signaling pathways both involved in the inhibition of cell proliferation. Finally, we showed that the increase of p21waf1/cip1 expression was generated by a Sp1‐dependent p53‐independent stimulation of its gene transcription as mutagenesis of the Sp1 binding sites located in the p21 proximal promoter abolished induction. To our knowledge, this is the first report showing that cladosporol A inhibits colon cancer cell proliferation by modulating p21waf1/cip1 expression. © 2011 Wiley Periodicals, Inc.
Multiple Criteria Decision Making (MCDM): From Paradigm Lost to Paradigm Regained?
Authors: Zeleny Milan
Published: October 2011

Because trade‐offs (Pareto optimal, non‐dominated or efficient sets) are not properties of criteria or objectives, but of sets of feasible alternatives, the proper task of decision making is to work on designing proper sets of alternatives rather than assuming them to be fixed and given a priori. In fact, decision making takes place only when multiple criteria and trade‐offs are present. All the rest (single criteria, aggregates or utilities) are simply analysis, measurement and search, not decision making.

Similarly, optimization must involve design of the configuration or ‘shape’ of sets of alternatives because no given and fixed system can be optimized. Traditional ‘optimization’ is therefore measurement and search, or just computation. Anything given and fixed a priori cannot be optimized. Multiple criteria or objectives can never be conflicting per se because their properties emerge only when applied to different sets of alternatives. Criteria are only ‘measure tapes’ and no trade‐offs can exist among them. Because decision making is incompatible with a single criterion, all decision making involves multiple criteria: thus, Multiple Criteria Decision Making (MCDM) becomes a redundant designation.

These and similar insights and conclusions call for MCDM paradigm re‐assessment: is it about decision making, or about analysis, measurement and search (explication) through computation? Eight different concepts of optimality are presented, as well as theories and models of trade‐offs elimination, conflict dissolution, optimal system design, de novo programming, theory of the displaced ideal and other advances related to feasible set optimal re‐design and re‐configuration. Copyright © 2011 John Wiley & Sons, Ltd.
Sample size requirements for the internal validation of psychiatric scales
Authors: Rouquette Alexandra , Falissard Bruno
Published: October 2011

The ratio of subjects to variables (N/p), as a rule to calculate the sample size required in internal validity studies on measurement scales, has been recommended without any strict theoretical or empirical basis being provided. The purpose of the present study was to develop a tool to determine sample size for these studies in the field of psychiatry. First, a literature review was carried out to identify the distinctive features of psychiatric scales. Then, two simulation methods were developed to generate data according to: (1) the model for factor structure derived from the literature review and (2) a real dataset. This enabled the study of the quality of solutions obtained from principal component analysis or Exploratory Factor Analysis (EFA) on various sample sizes. Lastly, the influence of sample size on the precision of Cronbach's alpha coefficient was examined. The N/p ratio rule is not upheld by this study: short scales do not allow smaller sample size. As a rule of thumb, if one's aim is to reveal the factor structure, a minimum of 300 subjects is generally acceptable but should be increased when the number of factors within the scale is large, when EFA is used and when the number of items is small. Copyright © 2011 John Wiley & Sons, Ltd.
Crisis and employment: The case of Korea
Authors: Cho Dongchul , Shin Sukha
Published: October 2011

This paper examines Korea's employment dynamics and analyzes how adverse impacts could be mitigated during the recent economic crisis in comparison with the 1997 to 1998 Asian crisis. A clear lesson is that policies to mitigate adverse impacts of financial crisis on the macroeconomic level should be given priority for preserving employment. In this regard, expansionary monetary and fiscal policies to keep aggregate demand from collapsing need to be emphasized once a crisis breaks out. However, equally crucial is the maintenance of sound pre‐crisis fundamentals to help keep negative impacts from proliferating, even when a crisis is triggered. In addition, flexible labor market structures and temporary employment‐boosting policies appear to be necessary to reduce the negative impacts of a crisis on workers. © 2011 by the Association for Public Policy Analysis and Management.
Parvovirus B19 infection and amniocentesis
Authors: Dick Oepkes , Eveline De Jong , frans Walther , Aloys Kroes
Published: October 2011

Abstract: Author's response to letter by Bogers et al. Copyright © 2011 John Wiley & Sons, Ltd.
Aortic isthmus blood flow in fetuses of diabetic mothers
Authors: Zielinsky Paulo , Frajndlich Renato , Nicoloso Luiz Henrique , Manica João Luiz Langer , Piccoli Antonio Luiz , de Morais Marina Resener , Bender Luciano , Silva Júlia , Pizzato Patrícia , Naujorks Alexandre
Published: October 2011

Objective

To test the hypothesis that the aortic isthmus flow index (IFI) is lower in fetuses of diabetic mothers than in fetuses of nondiabetic mothers.

Study Design

We performed a cross‐sectional observational study to assess the IFI in fetuses, with (n = 13) and without (n = 37) myocardial hypertrophy, of mothers with diabetes mellitus and in fetuses of nondiabetic mothers (n = 23). Analysis of variance and Tukey test were used to assess differences among the groups.

Results

There were no differences in maternal or gestational age among the groups. In fetuses of diabetic mothers, the mean IFI in fetuses with myocardial hypertrophy was 1.19 ± 0.06, and in fetuses without it was 1.18 ± 0.09. The mean IFI in fetuses of nondiabetic mothers was 1.32 ± 0.07 (P < 0.001).

Conclusions

The IFI in fetuses of diabetic mothers is lower than in fetuses of nondiabetic mothers, possibly as a result of a decreased left ventricular compliance. Copyright © 2011 John Wiley & Sons, Ltd.
Array CGH analysis in high‐risk pregnancies: comparing DNA from cultured cells and cell‐free fetal DNA
Authors: Gruchy Nicolas , Decamp Matthieu , Richard Nicolas , Jeanne‐Pasquier Corinne , Benoist Guillaume , Mittre Hervé , Leporrier Nathalie
Published: October 2011

Objective

To compare results of array comparative genomic hybridization (CGH) on cell‐free fetal (cff) DNA from amniotic fluid supernatant and DNA from cultured amniocytes in high‐risk pregnancies.

Method

We selected 48 cases of high‐risk pregnancies (in utero growth retardation [IUGR] and/or at least two fetal malformations [polymalformation]). Bacterial artificial chromosome array CGH (BlueGnome) was performed on 38 fetal samples (frozen cff DNA and DNA from cultured cells) with previously normal karyotypes.

Results

From the 38 specimens, we obtained an adequate amount of sufficient quality DNA with a better quality profile using cff DNA compared to cellular DNA.

Aberrations of clinical relevance were detected in three fetuses, and copy number variations considered as benign polymorphism were detected in one case using both sources of DNA. This results in an 8% detection rate of significant abnormalities in high‐risk pregnancies with a normal karyotype using array CGH (two cases with IUGR, one with polymalformation).

Conclusion

These findings indicate the possibility of using cff DNA from amniotic fluid supernatant for array CGH with excellent results, even in late pregnancy when culture is no longer available. In this small series, pathogenic copy number variations are detected more often in the presence of IUGR than with polymalformation. Copyright © 2011 John Wiley & Sons, Ltd.
Evolution of prenatal detection of neural tube defects in the pregnant population of the city of Barcelona from 1992 to 2006
Authors: Salvador Joaquín , Arigita Marta , Carreras Elena , Lladonosa Anna , Borrell Antoni
Published: October 2011

Objectives

To assess the prenatal ultrasound detection rates (DR) of neural tube defects (NTDs) and its evolution over the 1992 to 2006 period in the pregnant population of the city of Barcelona.

Methods

Data on the population‐based register of birth defects were used to assess the evolution of the prenatal DR for isolated NTD, including anencephaly, spina bifida and encephalocele by trimester of gestation.

Results

In the register, 127 isolated NTD cases, including 71 anencephalic fetuses, 49 spina bifidas and 7 encephaloceles were noted. Overall, prenatal ultrasound DR for isolated NTD was 94%. All fetuses with anencephaly or encephalocele were prenatally detected (100% DR), whereas DR for spina bifida was 84%, with no apparent variation over the observation period. An important increase in first trimester DRs was observed for anencephaly, rising from 16% in the first years of the study (1992–1996) to 71% in the last years (2002–2006).

Conclusion

A high DR (94%) for isolated NTD was observed in the city of Barcelona. The single significant change across the study period was an increase in the first trimester DR for anencephaly (from 16% to 71%). Copyright © 2011 John Wiley & Sons, Ltd.
Sheet bowing in thermoforming
Authors: Vodak P.B. , Mix A.W. , Giacomin A.J.
Published: October 2011

Sheets to be thermoformed are often heated unevenly, with a higher temperature above the sheet. This results in upward bowing of the sheet, and this is caused by thermal expansion. We combine the analytical solution for the temperature gradient in a slab heated by radiation with a relationship developed from the cylindrical geometry of the sheet as it bows. We thus derive a dimensionless equation for sheet bowing as an implicit function of time for both top and dual heating. We thus uncover a new dimensionless group which we call sheet bowability. We find good agreement between our theory and our new top‐heated sheet bowing measurements. We provide a worked example so that the engineer can see how to apply our results. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers