bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine‐needle aspiration diagnosis of an intraosseous amyloidoma
Authors: Factor Rachel E. , Layfield Lester J. , Grossmann Allie H. , Crim Julia R. , Price Shawn L. , Randall RL
Published: May 2011

Fine‐needle aspiration (FNA) is frequently used as the initial diagnostic procedure for the investigation of bone and soft tissue masses. The majority of the lesions detected will represent metastatic carcinoma. Amyloid is a rare cause of a bone mass, with less than 15 published reports describing amyloid deposition within bone. The majority of reported cases involve the vertebral column. We report the finding of a massive amyloidoma of the iliac wing in a 46‐year‐old man. FNA smears and cell block preparations demonstrated fragments of waxy acellular material misinterpreted as necrotic debris. Subsequent open biopsy established the diagnosis of amyloid with congo red staining demonstrating apple green birefringence. Subsequent workup disclosed the patient to have anemia, hypogammaglobulinemia and trace monoclonal light chain gammopathy. Bone marrow examination revealed CD138a positive lambda restricted plasma cells consistent with plasma cell dyscrasia. Careful attention to the staining characteristics of amyloid in FNA derived material should allow the diagnosis of amyloidoma. 2012. © 2011 Wiley Periodicals, Inc.
Morphometric image analysis of pancreatic disease by ThinPrep liquid‐based cytology
Authors: Taira Tomoki , Kawahara Akihiko , Yamaguchi Tomohiko , Abe Hideyuki , Ishida Yusuke , Okabe Yoshinobu , Naito Yoshiki , Yano Hirohisa , Kage Masayoshi
Published: May 2011

Liquid‐based cytology preparations are being increasingly used in nongynecologic specimens. The aim of this study is to objectively evaluate pancreatic disease by ThinPrep (TP) liquid‐based cytology using morphometric image analysis. In all, 30 patients undergoing preoperative evaluation of pancreatic disease by TP were investigated from January to April 2009. We analyzed cytological features, such as cluster area, cluster circularity, and nucleus area, using morphometric image analysis software and further investigated the cytological findings of TP to determine which are useful for detecting malignancy. Pancreatic cytological findings of TP showed small clusters and loss of cluster irregularity in malignant cells. The patients were diagnostically categorized as inadequate, normal or benign, indeterminate, suspected malignancy, and malignant in 6.6% (2), 46.7% (14), 13.3% (4), 13.3% (4), and 20.0% (6) of the cases, respectively. Morphometric image analysis of 28 patients by TP,excluding two inadequate patients, showed no statistical difference in cluster area or cluster circularity among these cytological categories. In contrast, nucleus area in the normal or benign, indeterminate, suspected malignancy, and malignant categories was 17.6, 57.2, 67.4, and 68.0 μm2, respectively, and was associated with diagnostic category (P < 0.05). Pancreatic cytological findings of TP preparations generally show small, round cluster shapes in pancreatic disease; however, nucleus size is a more important criteria for detecting malignancy by TP in pancreatic disease. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Cytomorphologic findings of Schneiderian papilloma: A case report
Authors: Rodic Nemanja , Maleki Zahra
Published: May 2011

Schneiderian papilloma or inverted papilloma (IP) is the most common sinonasal papilloma yet a rare tumor with the greatest potential for recurrence and local destruction and association with malignant transformation. Tissue biopsy is routinely performed to examine these lesions. However, Fine needle aspiration may provide an immediate diagnosis. Herein, we report cytomorphologic findings of IP in a 46‐year‐old man with histopathologic correlation and review of the literature. 2012. © 2011 Wiley Periodicals, Inc.
Paget's disease of the breast masquerading as squamous cell carcinoma on cytology: A case report
Authors: Vohra Poonam , Ljung Britt‐Marie E. , Miller Theodore R. , Hwang Eun‐Sil , van Zante Annemieke
Published: May 2011

Paget's disease is an uncommon manifestation of breast carcinoma occurring in 1–2% of female patients with breast cancer. Here, we present a case of Paget's disease of the breast, which was initially interpreted as squamous cell carcinoma on cytology. This case report raises two issues. First, histological and cytological specimens of Paget's disease show a mixed population of epithelial cells including squamous cells with reactive changes and malignant glandular cells. In the current case, a mixed population of atypical keratinizing and nonkeratinizing epithelial cells was initially interpreted as squamous cell carcinoma of cutaneous origin. The marked reactive changes in the squamous epithelium involved by Paget's disease should be recognized. Second, this case is an unusual clinical presentation for Paget's disease of the breast as the nipple‐areolar complex and underlying breast tissue were surgically absent at the time of diagnosis. Clinical suspicion, along with an awareness of the cytologic features and clinical presentation of Paget's disease, can help in reaching the correct diagnosis in a timely fashion. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
The diagnostic reliability of urinary cytology: A retrospective study
Authors: Raisi O. , Magnani C. , Bigiani N. , Cianciavicchia E. , D'Amico R. , Muscatello U. , Ghirardini C.
Published: May 2011

The aim of this study was twofold. The first aim was to estimate the diagnostic reliability of urinary cytology for detection and management of urothelial neoplasms by using a specific preserving fluid for sample collection, and the liquid‐based thin layer method for specimen preparation, the estimate was based on the correlation between the cytological findings of 10,000 non‐hospitalized patients, and their histological diagnoses. A second aim was to compare the reliability of two instruments for thin‐layer preparation, i.e., TP2000, TP3000, capable of processing the specimens at very different rates. The preservation of cell structure is ameliorated by the procedure of sample collection and treatment here described. This allows a more accurate reading of LBC slides as shown by: (a) the significant concordance between cytological and histological diagnosis (92%); (b) the significant number of low‐grade urothelial carcinomas (20.5%) revealed by urinary cytology and validated by histologic diagnosis; (c) the low rate (8%) of misjudgement of cytological diagnosis reached in this study. The quality of performances of the two instruments tested for thin‐layer preparation, i.e., TP2000 and TP3000, is statistically comparable. We recommend the procedure that makes use of preserving fluid for sample collection (cytolyt™) and treatment (preservcyt ™) as here described. We also recommend the use of thin‐layer method for specimen preparation since it allows a more uniform distribution of the cells on the support with reduction of overlapping phenomena. Finally, economic considerations suggest the preferential use of Thin Prep 3000. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Transfer Hydrogenation of Ketones and Activated Olefins Using Chelating NHC Ruthenium Complexes
Authors: Horn Sabine , Gandolfi Claudio , Albrecht Martin
Published: May 2011

N‐Heterocyclic carbene (NHC) ruthenium complexes consisting of different donor substituents attached to the NHC ligand efficiently catalyse the transfer hydrogenation of ketones and of activated olefins in α,β‐unsaturated ketones to give saturated alcohols. The most active catalyst precursor contains a tethered olefin as a hemilabile donor site. This complex also converts nitriles and, depending on the reaction conditions, either benzylamines are produced by means of transfer hydrogenation, or amides from formal addition of H2O. Kinetic analysis of the double hydrogenation of α,β‐unsaturated ketones indicates fast isomerisation of the enol intermediate to its saturated ketone tautomer prior to the second hydrogenation.
Bidentate Lewis Acids for the Activation of 1,2‐Diazines – A New Mode of Catalysis
Authors: Kessler Simon N. , Neuburger Markus , Wegner Hermann A.
Published: May 2011

Bidentate Lewis acids were applied as catalysts for the inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 1,2‐diazines. The concept of catalysis is based on the coordination of the bidentate Lewis acid to both nitrogen atoms of the 1,2‐diazine moiety, thereby reducing the electron density and lowering the energy of the LUMO. This should, according to frontier molecular orbital (FMO) theory, facilitate the cycloaddition step. This new concept was successfully applied to a variety of dienophiles and substituted phthalazine substrates. Careful investigations of the mechanism led to the isolation and characterization of key intermediates; all of which support the presented catalytic cycle.
The Dinosyl Group: A Powerful Activator for the Regioselective Alcoholysis of Aziridines
Authors: Stanetty Christian , Blaukopf Markus K. , Lachmann Bodo , Noe Christian R.
Published: May 2011

The N‐2,4‐dinitrophenylsulfonyl group (dinosyl, DNs) was found to be an excellent choice for the N‐activation of aziridines towards ring cleavage with primary, secondary, andsterically demanding tertiary alcohols. Alcoholysis does not need any additional catalyst and is regioselective for the less‐hindered position. No racemization in the aziridine formation or cleavage step was observed, and the resulting DNs‐sulfonamides can be deprotected quantitatively under mild conditions.
Fluid–structure interaction analysis in microfluidic devices: A dimensionless finite element approach
Authors: Afrasiab Hamed , Movahhedy Mohammad R. , Assempour Ahmad
Published: May 2011

In this paper, the so‐called small time‐step instability in finite element simulation of the fluid part is considered in fluid–structure interaction (FSI) problems in which a high‐frequency vibrating structure interacts with an incompressible fluid. Such a situation is common in many microfluid manipulating devices. A treatment has been proposed that uses the dimensionless set of FSI governing equations in order to scale up the problem time step to a proper level that precludes the potential small time‐step instability. Two‐dimensional and three‐dimensional finite element simulations of a mechanical micropumping device are performed to verify the efficiency of the presented approach. Solid structure vibrations of high frequency and nano‐scale amplitude are used to derive the fluid flow in this kind of micropump. Results of FEM simulations are in good agreement with experimental data. The fluid problem is formulated and solved in arbitrary Lagrangian–Eulerian description. Copyright © 2011 John Wiley & Sons, Ltd.
Astrocytic activation of A1 receptors regulates the surface expression of NMDA receptors through a Src kinase dependent pathway
Authors: Deng Qiudong , Terunuma Miho , Fellin Tommaso , Moss Stephen J. , Haydon Philip G.
Published: May 2011

Chemical transmitters released from astrocytes, termed gliotransmitters, modulate synaptic transmission and neuronal function. Using astrocyte‐specific inducible transgenic mice (dnSNARE mice), we have demonstrated that inhibiting gliotransmission leads to reduced activation of adenosine A1 receptors (A1R) and impaired sleep homeostasis (Halassa et al. (2009) Neuron 61:213–219); Pascual et al. (2005) Science 310:113–116). Additionally, synaptic N‐methyl‐D‐aspartate receptor (NMDAR) currents are reduced in these astrocyte‐specific transgenic animals (Fellin et al. (2009) Proc Natl Acad Sci USA 106:15037–15042). Because of the importance of adenosine and NMDA receptors to sleep processes we asked whether there is a causal linkage between changes in A1R activation and synaptic NMDA receptors. We show that astrocytic dnSNARE expression leads to reduced tyrosine phosphorylation of Src kinase and NR2 subunits concomitant with the decreased surface expression of the NR2 subunits. To test the role of A1R signaling in mediating these actions, we show that incubation of wildtype (WT) slices with an A1R antagonist reduces tyrosine phosphorylation of Src kinase and NR2B, decreases the surface expression of the NR2B subunits and leads to smaller NMDA component of miniature EPSCs. In dnSNARE mice we could rescue WT phenotype by incubation in an A1R agonist: activation of A1 receptor led to increased tyrosine phosphorylation of Src kinase and NR2B subunits as well as increased the surface expression of the NR2B subunit and increased NMDA component of the synaptic mEPSC. These results provide the first demonstration that astrocytes can affect neuronal excitability on a long time scale by regulating the surface expression of NMDA receptors through the activation of specific intracellular signaling pathways. © 2011 Wiley‐Liss, Inc.
Differentiation of postnatal cerebellar glial progenitors is controlled by Bmi1 through BMP pathway inhibition
Authors: Zhang Xinyu , Santuccione Antonella , Leung Carly , Marino Silvia
Published: May 2011

Bmi1 is a polycomb group (Pc‐G) protein involved in heritable gene repression, maintenance of cell identity, and proliferation. During the development of the central nervous system, Bmi1 is crucial for self‐renewal of neural stem cells and for proliferation of neuronal (granule cell) progenitors of the cerebellum. Here, we use loss of function mouse models and in vitro assays—granule cell cultures and glial‐neuronal co‐cultures—to show that Bmi1 plays a crucial role in specification of glial progenitors during postnatal cerebellar development. Moreover, we demonstrate in in vitro assays that Bmi1 exerts this novel function through repression of BMP pathway and that this is independent of its known role in mediating the cellular response to Shh signaling. Thus modulation of Bmi1 expression in glial progenitors may represent a key event in determining the differentiation potential of these cells. © 2011 Wiley‐Liss, Inc.
Novel molecular targeted therapies for refractory thyroid cancer
Authors: Perez Cesar A. , Santos Edgardo S. , Arango Belisario A. , Raez Luis E. , Cohen Ezra E. W.
Published: May 2011

The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine‐refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B‐Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR‐2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi‐kinase inhibitors such as axitinib, sorafenib, motesanib, and XL‐184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Chondromyxoid fibroma of the nasal septum: Case report and review of literature
Authors: McClurg Stanley W. , Leon Marino , Teknos Theodoros N. , Iwenofu O. Hans
Published: May 2011

Background.

Chondromyxoid fibroma (CMF) is a rare bone tumor, accounting for less than 0.5% of all bone tumors, with a predilection for lower extremity bone metaphyses. Involvement of the head and neck is extremely rare, with only 3 cases reported in the nasal septum in world literature.

Methods.

This is a case report of a CMF in the nasal septum of a 49‐year‐old woman with a 6‐month history of congestion. MRI showed a bilobed mass originating from the nasal septum. Histologic and immunoperoxidase staining as well as electron microscopic studies were performed. A literature review was performed.

Results.

The patient underwent a midface‐degloving approach for surgical resection. The final pathology was prototypic of CMF. The patient was disease‐free 16 months postoperatively.

Conclusions.

CMF is a rare, benign neoplasm occasionally occurring in the head and neck. Surgical resection is often curative. CMF must be differentiated from chondrosarcoma, given the substantial differences in treatment. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Circulating micro‐RNA expression profiles in early stage nonsmall cell lung cancer
Authors: Heegaard Niels H.H. , Schetter Aaron J. , Welsh Judith A. , Yoneda Mitsuhiro , Bowman Elise D. , Harris Curtis C.
Published: May 2011

Circulating micro‐RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro‐RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT‐PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro‐RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR‐146b, miR‐221, let‐7a, miR‐155, miR‐17‐5p, miR‐27a and miR‐106a were significantly reduced in the serum of NSCLC cases, while miR‐29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let‐7b was modestly associated with worse cancer‐specific mortality in all patients, and reduced serum expression of miR‐223 was modestly associated with cancer‐specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let‐7b is associated with prognosis in NSCLC.
Anti‐tumour/metastasis effects of the potassium‐sparing diuretic amiloride: An orally active anti‐cancer drug waiting for its call‐of‐duty?
Authors: Matthews Hayden , Ranson Marie , Kelso Michael J.
Published: May 2011

Amiloride.HCl is clinically used as an oral potassium‐sparing diuretic, but multiple studies in biochemical, cellular and animal models have shown that the drug also possesses anti‐tumour and anti‐metastasis activities. The additional effects appear to arise through inhibition of two discrete targets: (i) the sodium–hydrogen exchanger 1 (NHE1), a membrane protein responsible for the characteristically low extracellular pH of tumours and (ii) the urokinase‐type plasminogen activator (uPA), a serine protease mediator of cell migration, invasion and metastasis and well‐known marker of poor prognosis in cancer. This mini‐review summarises for the first time the reported anti‐tumour/metastasis effects of amiloride in experimental models, discusses the putative molecular mechanisms responsible for these effects and concludes by commenting on the pros and cons of trialling amiloride or one of its structural analogues as potential new anti‐tumour/metastasis drugs.
Quinacrine has anticancer activity in breast cancer cells through inhibition of topoisomerase activity
Authors: Preet Ranjan , Mohapatra Purusottam , Mohanty Suchitra , Sahu Sushil Kumar , Choudhuri Tathagata , Wyatt Michael D. , Kundu Chanakya Nath
Published: May 2011

The small molecule Quinacrine (QC, a derivative of 9‐aminoacridine), an anti‐malaria drug, displays activity against cancer cell lines and can simultaneously suppress nuclear factor‐κB (NF‐κB) and activate p53 signaling. In this study, we investigated the anticancer mechanism underlying these drug activities in breast cancer cell lines. QC caused a dose‐dependent decrease of both anchorage dependent and independent growth of breast cancer cells (MCF‐7 and MDA‐MB‐231) without affecting normal breast epithelial cells (MCF‐10A), as evident from clonogenic cell survival, [3‐(4,5‐dimethylthiazol‐2yl‐)‐2,5‐diphenyl tetrazolium bromide] viability, wound healing and soft agar growth. QC activated the proapoptotic marker Bax, PARP cleavage, p53 and its downstream target, p21 (Cip1/Waf1) and downregulated the antiapoptotic marker Bcl‐xL and relative luciferase activity of NF‐κB in MCF‐7 cells. Results of DAPI nuclear staining and FACS analysis show that QC increased apoptosis in a dose‐dependent manner. QC caused apoptosis by increasing the cell population in S‐phase and simultaneously decreasing the G1 and G2/M populations. A dose‐dependent increase of DNA damage as measured by the comet assay was seen in MCF‐7 cells after exposure to QC. With regards to the mechanism of DNA damage, we found that QC inhibited topoisomerase activity in MCF‐7 cells by increasing the unwinding of supercoiled DNA. Collectively, the results demonstrate that QC has efficient anticancer potential against breast cancer cells via not only an induction of p53 and p21 but also an induction of S phase arrest, DNA damage and inhibition of topoisomerase activity.
Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma
Authors: Nagata Masayoshi , Sakurai‐Yageta Mika , Yamada Daisuke , Goto Akiteru , Ito Akihiko , Fukuhara Hiroshi , Kume Haruki , Morikawa Teppei , Fukayama Masashi , Homma Yukio , Murakami Yoshinori
Published: May 2011

Renal clear cell carcinoma (RCCC) is the most frequent subpopulation of renal cell carcinoma and is derived from the proximal uriniferous tubules. We have previously reported that an actin‐binding protein, 4.1B/DAL‐1, is expressed in renal proximal tubules, whereas it is inactivated in 45% of RCCC by promoter methylation. In the lung and several epithelial tissues, 4.1B is shown to associate with a tumor suppressor protein, CADM1, belonging to the immunoglobulin‐superfamily cell adhesion molecules. Here, we demonstrate by immunohistochemistry that another member of the CADM‐family protein, CADM4, as well as 4.1B is expressed specifically in human proximal tubules, while CADM1 and 4.1N, another member of the 4.1 proteins, are expressed in the distal tubules. Immunoprecipitation analysis coupled with Western blotting revealed that CADM4 associated with 4.1B, while CADM1 associated with 4.1N in the lysate from normal human kidney, implicating that a cascade of CADM4 and 4.1B plays an important role in normal cell adhesion of the proximal tubules. On the other hand, CADM4 expression was lost or markedly reduced in 7 of 10 (70%) RCC cell lines and 28 of 40 (70%) surgically resected RCCC, including 10 of 16 (63%) tumors with T1a. CADM4 expression was more preferentially lost in RCCC with vascular infiltration (p = 0.04), suggesting that loss of CADM4 is involved in tumor invasion. Finally, introduction of CADM4 into an RCC cell line, 786‐O, dramatically suppressed tumor formation in nude mice. These findings suggest that CADM4 is a novel tumor suppressor candidate in RCCC acting with its binding partner 4.1B.
Body fat distribution, weight change during adulthood, and thyroid cancer risk in the NIH‐AARP Diet and Health Study
Authors: Kitahara Cari M. , Platz Elizabeth A. , Park Yikyung , Hollenbeck Albert R. , Schatzkin Arthur , Berrington de González Amy
Published: May 2011

Body mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH‐AARP Diet and Health Study who completed a second mailed questionnaire in 1996–1997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow‐up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: >102 cm in men and >88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.21–2.63) and women (HR = 1.54, 95% CI: 1.05–2.26). Having both a large waist and BMI in the obese range (≥30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.18–3.85; HR in women = 1.91, 95% CI: 1.31–3.25) compared to having a normal waist circumference/normal BMI (18.5–24.9 kg/m2). We also observed positive association for weight gain between ages 18–35 in men (gained ≥10.0 kg vs. lost/gained <5 kg, HR = 1.49, 95% CI: 0.93–2.39, p‐trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.
Genetic variability in the metabolism of the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) to 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL)
Authors: Ter‐Minassian Monica , Asomaning Kofi , Zhao Yang , Chen Feng , Su Li , Carmella Steven G. , Lin Xihong , Hecht Stephen S. , Christiani David C.
Published: May 2011

Urinary metabolites of the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL) and its glucuronides, termed total NNAL, have recently been shown to be good predictors of lung cancer risk, years before diagnosis. We sought to determine the contribution of several genetic polymorphisms to total NNAL output and inter‐individual variability. The study subjects were derived from the Harvard/Massachusetts General Hospital Lung cancer case‐control study. We analyzed 87 self‐described smokers (35 lung cancer cases and 52 controls), with urine samples collected at time of diagnosis (1992–1996). We tested 82 tagging SNPs in 16 genes related to the metabolism of NNK to total NNAL. Using weighted case status least squares regression, we tested for the association of each SNP with square‐root (sqrt) transformed total NNAL (pmol per mg creatinine), controlling for age, sex, sqrt packyears and sqrt nicotine (ng per mg creatinine). After a sqrt transformation, nicotine significantly predicted a 0.018 (0.014, 0.023) pmol/mg creatinine unit increase in total NNAL for every ng/mg creatinine increase in nicotine at p < 10E‐16. Three HSD11B1 SNPs and AKR1C4 rs7083869 were significantly associated with decreasing total NNAL levels: HSD11B1 rs2235543 (p = 4.84E‐08) and rs3753519 (p = 0.0017) passed multiple testing adjustment at FDR q = 1.13E‐05 and 0.07 respectively, AKR1C4 rs7083869 (p = 0.019) did not, FDR q = 0.51. HSD11B1 and AKR1C4 enzymes are carbonyl reductases directly involved in the single step reduction of NNK to NNAL. The HSD11B1 SNPs may be correlated with the functional variant rs13306401 and the AKR1C4 SNP is correlated with the enzyme activity reducing variant rs17134592, L311V.
Candidate driver genes in microsatellite‐unstable colorectal cancer
Authors: Alhopuro Pia , Sammalkorpi Heli , Niittymäki Iina , Biström Mia , Raitila Anniina , Saharinen Juha , Nousiainen Kari , Lehtonen Heli J. , Heliövaara Elina , Puhakka Jani , Tuupanen Sari , Sousa Sónia , Seruca Raquel , Ferreira Ana M. , Hofstra Robert M. W. , Mecklin Jukka‐Pekka , Järvinen Heikki , Ristimäki Ari , Ørntoft Torben F. , Hautaniemi Sampsa , Arango Diego , Karhu Auli , Aaltonen Lauri A.
Published: May 2011

Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in ∼ 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers. Here, we evaluated somatic mutations in microsatellite repeats of 790 genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat of 6–10 bp in length. All the repeats were initially sequenced in 30 primary MSI CRC samples and whenever frameshift mutations were identified in >20%, additional 70 samples were sequenced. To distinguish driver mutations from passengers, we similarly analyzed the occurrence of frameshift mutations in 121 intronic control repeats and utilized a statistical regression model to determine cut‐off mutation frequencies for repeats of all types (A/T and C/G, 6–10 bp). Along with several know target genes, including TGFBR2, ACVR2, and MSH3, six novel candidate driver genes emerged that harbored significantly more mutations than identical control repeats. The mutation frequencies in 100 MSI CRC samples were 51% in G8 of GLYR1, 47% in T9 of ABCC5, 43% in G8 of WDTC1, 33% in A8 of ROCK1, 30% in T8 of OR51E2, and 28% in A8 of TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in tumors carrying biallelic mutations, supporting a loss of function hypothesis. This is a large scale, unbiased effort to identify genes that when mutated are likely to contribute to MSI CRC development.
Targeting of pancreatic and prostate cancer stem cell characteristics by Crambe crambe marine sponge extract
Authors: Ottinger Sabine , Klöppel Anne , Rausch Vanessa , Liu Li , Kallifatidis Georgios , Gross Wolfgang , Gebhard Martha‐Maria , Brümmer Franz , Herr Ingrid
Published: May 2011

Cancer stem cells (CSCs) are suggested as reason for resistance of tumors toward conventional tumor therapy including pancreatic and advanced prostate cancer. New therapeutic agents are urgently needed for targeting of CSCs. Marine sponges harbor novel and undefined compounds with antineoplastic activity but their potential to eliminate CSC characteristics is not examined so far. We collected 10 marine sponges and one freshwater sponge by diving at the seaside and prepared crude methanolic extracts. The effect to established pancreatic and prostate CSC lines was evaluated by analysis of apoptosis, cell cycle, side population, colony and spheroid formation, migratory potential in vitro and tumorigenicity in vivo. While each sponge extract at a 1:10 dilution efficiently diminished viability, Crambe crambe marine sponge extract (CR) still strongly reduced viability of tumor cells at a dilution of 1:1,000 but was less toxic to normal fibroblasts and endothelial cells. CR inhibited self‐renewal capacity, apoptosis resistance, and proliferation even in gemcitabine‐selected pancreatic cancer cells with acquired therapy resistance and enhanced CSC characteristics. CR pretreatment of tumor cells diminished tumorigenicity of gemcitabine‐resistant tumor cells in mice and totally abolished tumor take upon combination with gemcitabine. Our data suggest that CR contains substances, which render standard cancer therapy more effective by targeting of CSC characteristics. Isolation of bioactive metabolites from CR and evaluation in mice are required for development of new CSC‐specific chemotherapeutic drugs from a marine sponge.
DEALING WITH SEDIMENTATION ISSUES IN SPATE IRRIGATION SYSTEMS
Authors: Embaye T. G. , Beevers L. , Mehari Haile A.
Published: May 2011

With growing water variability and scarcity in Africa a reality, a renewed interest in spate irrigation systems, which harness water in ephemeral environments, has emerged. Spate irrigation is seen as practical solution to supplement food production and improve food security in areas where water supply is scarce or highly variable. The political will in support of the system is evident in countries like Ethiopia, where significant investment is currently underway to upgrade the system.

While the potential exists, the actual contribution of spate irrigation systems to food security has, so far, not been significant. One of the major reasons is the very high sedimentation rates of canals and irrigated fields. In spate irrigation systems sediment is a double‐edged sword. Fine sediment brings fertility and makes it possible to build up well‐structured soils, while on the other hand coarser sediment reduces spate flow diversion efficiency, raises the bed level and removes fields from the irrigation command. As is the case in several other countries, the spate irrigation systems in Ethiopia that were modernized through conventional civil engineering practices, lack effective technical and operational measures that maximize the benefits of sediments. To address this particular problem, a study was conducted in the Fokisa Spate Irrigation System in Ethiopia. The study employed field observations and simulations with various one‐dimensional hydraulic models. Primarily based on the study, but also drawing from experience in other spate irrigation systems, this paper analyses the effectiveness of settling basins and canal designs with non‐uniform cross sections and varying slopes. The results indicate that settling basins are not an optimal alternative and that designing canals with non‐uniform sections and slope leads to better performance. It is concluded that the former are not applicable in spate systems. Copyright © 2011 John Wiley & Sons, Ltd.
Optical diagnostic test of stress conditions of aquatic organisms
Authors: Axenov‐Gribanov Denis V. , Gurkov Anton N. , Shakhtanova Nadezhda S. , Bedulina Daria S. , Timofeyev Maxim A. , Meglinski Igor
Published: May 2011

Global climate change has become a dire reality and its impact is expected to rise dramatically in the near future. Combined with the day‐to‐day human activities the climatic changes heavily affect the environment. In particular, a global temperature increase accompanied by a number of anthropogenic chemicals falling within the freshwater ecosystem results in a dramatic enhancement of the overall stress for most aquatic organisms. This leads to a significant shift in the species inventory and potential breakdown of the water ecosystem with severe consequences for local economies and water supply. In order to understand and predict the influence of climatic changes on the physiological and biochemical processes that take place in living aquatic organisms we explore the application of optical spectroscopy for monitoring and quantitative assessment of antioxidant enzymes activity in benthic amphipods of Lake Baikal. We demonstrate that the changes of the enzymes activity in Baikal amphipods undergoing thermal and/or hypoxia stress can be observed and documented by UV and optical spectroscopy both in vivo and in vitro. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Intraperitoneal adhesions—an ongoing challenge between biomedical engineering and the life sciences
Authors: Brochhausen Christoph , Schmitt Volker H. , Rajab Taufiek K. , Planck Constanze N. E. , Krämer Bernhard , Wallwiener Markus , Hierlemann Helmut , Kirkpatrick C. James
Published: May 2011

Peritoneal adhesions remain a relevant clinical problem despite the currently available prophylactic barrier materials. So far, the physical separation of traumatized serosa areas using barriers represents the most important clinical strategy for adhesion prevention. However, the optimal material has not yet been found. Further optimization or pharmacological functionalization of these barriers could give an innovative input for peritoneal adhesion prevention. Therefore, a more complete understanding of pathogenesis is required. On the basis of the pathophysiology of adhesion formation the main barriers currently in clinical practice as well as new innovations are discussed in the present review. Physiologically, mesothelial cells play a decisive role in providing a frictionless gliding surface on the serosa. Adhesion formation results from a cascade of events and is regulated by a variety of cellular and humoral factors. The main clinically applied strategy for adhesion prevention is based on the use of liquid or solid adhesion barriers to separate physically any denuded tissue. Both animal and human trials have not yet been able to identify the optimal barrier to prevent adhesion formation in a sustainable way. Therefore, further developments are required for effective prevention of postoperative adhesion formation. To reach this goal the combination of structural modification and pharmacological functionalization of barrier materials should be addressed. Achieving this aim requires the interaction between basic research, materials science and clinical expertise. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Degradation, cytotoxicity, and biocompatibility of NIPAAm‐based thermosensitive, injectable, and bioresorbable polymer hydrogels
Authors: Cui Zhanwu , Lee Bae Hoon , Pauken Christine , Vernon Brent L.
Published: May 2011

A thermosensitive, injectable, and bioresorbable polymer hydrogel, poly(N‐isopropylacrylamide‐co‐dimethyl‐γ‐butyrolactone acrylate‐co‐acrylic acid) [poly(NDBA)], was synthesized by radical copolymerization with 7.00 mol % dimethyl‐γ‐butyrolactone acrylate in tetrahydrofuran. The chemical composition was determined by acid titration in conjunction with 1H NMR quantification. The molecular weight and polydispersity were determined by gel permeation chromatography in conjunction with static light scattering. The degradation properties of the polymer hydrogel were characterized using differential scanning calorimetry, percentage mass loss, cloud point test, and swelling ratio over time. It was found that the initial lower critical solution temperature (LCST) of the polymer is between room temperature and body temperature and that it takes about 2 weeks for the LCST to surpass body temperature under physiological conditions. An indirect cytotoxicity test indicated that this copolymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells. The in vivo‐gelation and degradation study showed good agreement with in vitro‐degradation findings, and no detrimental effects to adjacent tissues were observed after the complete dissolution of the polymer. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Development of bioactive photocrosslinkable fibrous hydrogels
Authors: Stephens‐Altus J. S. , Sundelacruz P. , Rowland M. L. , West J. L.
Published: May 2011

Three‐dimensional (3D) fibrous hydrogels were fabricated by blending two photoactive polymers, poly(ethylene glycol) diacrylate (PEGDA) and poly(vinyl alcohol) (PVA), and the resulting solution was electrospun. PEGDA is a commonly used hydrogel material for tissue engineering applications since its interaction with cells can be tuned by crosslinking in a variety of bioactive molecules including peptides and proteins. The PVA in these materials aids in fiber formation and stabilizes the fibrous network when hydrated. The average dry fiber diameter in the hydrogels was 1.02 μm and upon swelling, the fiber diameter increased approximately six‐fold. Fibers were stable under cell culture conditions for up to 5 days. The adhesive ligand, RGDS, was readily incorporated into the fibrous network via the conjugation of RGDS to PEG‐monoacrylate which was then crosslinked with the fibers. The bioactivity of the fibrous hydrogels was compared with peptide‐modified PEGDA‐based hydrogels. The two hydrogel materials had similar cell adhesion and viability. Cell morphology on the fibrous hydrogels was dendritic showing a more in vivo like representation, as compared to spread cell morphology on the PEGDA gels. The ability to generate 3D fibrous architectures in hydrogel systems opens up new areas of investigation in cell‐material interactions and tissue formation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
The ionic products of bioactive glass particle dissolution enhance periodontal ligament fibroblast osteocalcin expression and enhance early mineralized tissue development
Authors: Varanasi Venu G. , Owyoung Jeremy B. , Saiz Eduardo , Marshall Sally J. , Marshall Grayson W. , Loomer Peter M.
Published: May 2011

This study resulted in enhanced collagen type 1 and osteocalcin expression in human periodontal ligament fibroblasts (hPDLF) when exposed to bioactive glass conditioned media that subsequently may promote early mineralized tissue development. Commercial Bioglass™ (45S5) and experimental bioactive coating glass (6P53‐b), were used to make a glass conditioned media (GCM) for comparison to control medium. ICP‐MS analysis showed increased concentrations of Ca2+, PO43−, Si4+, and Na+, for 45S5 GCM and Mg2+, K+, Ca2+, PO43−, Si4+, and Na+ for 6P53‐b GCM (relative to control medium). Differentiating hPDLF cultures exposed to 45S5 and 6P53‐b GCM showed enhanced expression of collagen type 1 (Col1α1, Col1α2), osteocalcin, and alkaline phosphatase gene expression. These GCM also enhanced osteocalcin protein expression. After 16 d of culture, 45S5 and 6P53‐b GCM treated cells showed regions of deep red Alizarin staining, indicating increased Ca within their respective extracellular matrices (ECM), while control‐treated cells did not exhibit these features. SEM analysis showed more developed ECM in GCM treated cultures, indicated by multiple tissue layering and abundant collagen fiber bundle formation, while control treated cells did not exhibit these features. SEM analysis showed polygonal structures suggestive of CaP in 45S5 GCM treated cultures. These results indicate the osteogenic potential of bioactive coating glass in periodontal bone defect filling applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
In situ forming poly(ethylene glycol)‐based hydrogels via thiol‐maleimide Michael‐type addition
Authors: Fu Yao , Kao Weiyuan John
Published: May 2011

The incorporation of cells and sensitive compounds can be better facilitated without the presence of UV or other energy sources that are common in the formation of biomedical hydrogels such as poly(ethylene glycol) hydrogels. The formation of hydrogels by the step‐growth polymerization of maleimide‐ and thiol‐terminated poly(ethylene glycol) macromers via Michael‐type addition is described. The effects of macromer concentration, pH, temperature, and the presence of biomolecule gelatin on gel formation were investigated. Reaction kinetics between maleimide and thiol functional groups were found to be rapid. Molecular weight increase over time was characterized via gel permeation chromatography during step‐growth polymerization. Swelling and degradation results showed incorporating gelatin enhanced swelling and accelerated degradation. Increasing gelatin content resulted in the decreased storage modulus (G′). The in vitro release kinetics of fluorescein isothiocyanate (FITC)‐labeled dextran from the resulting matrices demonstrated the potential in the development of novel in situ gel‐forming drug delivery systems. Moreover, the resulting networks were minimally adhesive to primary human monocytes, fibroblasts, and keratinocytes thus providing an ideal platform for further biofunctionalizations to direct specific biological response. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Relationship between vitamin D status and bone mineralization, mass, and metabolism in children with osteogenesis imperfecta: Histomorphometric study
Authors: Edouard Thomas , Glorieux Francis H , Rauch Frank
Published: May 2011

The effect of low vitamin D levels in children with bone fragility disorders has not been examined in detail. In this study, we evaluated the relationship between vitamin D status and parameters of skeletal mineralization, mass, and metabolism in a group of pediatric osteogenesis imperfecta (OI) patients. This retrospective study consisted of 71 patients with a diagnosis of OI type I, III, or IV (ages 1.4 to 17.5 years; 36 girls) who had not received bisphosphonate treatment before iliac bone biopsy. Serum 25-hydroxyvitamin D [25(OH)D] levels ranged from 13 to 103 nmol/L and were less than 50 nmol/L in 37 patients (52%). None of the OI patients had radiologic signs of rickets or fulfilled the histomorphometric criteria for the diagnosis of osteomalacia (ie, elevated results for both osteoid thickness and mineralization lag time). Serum 25(OH)D levels were negatively correlated with age and serum parathyroid hormone levels but were not correlated with any parameter of bone mineralization (ie, osteoid thickness, mineralization lag time, or bone-formation rate per bone surface) or bone mass (ie, lumbar spine areal bone mineral density, iliac bone volume per tissue volume, or iliac cortical width). We found no evidence that serum 25(OH)D levels in the range from 13 to 103 nmol/L were associated with measures of bone mineralization, metabolism, or mass in children with OI. © 2011 American Society for Bone and Mineral Research
Inhibitory effect of thrombin on the expression of secretory group IIA phospholipase A2
Authors: Bae Jong‐Sup
Published: May 2011

It is well known that the expression level of secretory group IIA phospholipase A2 (sPLA2‐IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS) up‐regulates the expression of sPLA2‐IIA in human umbilical vein endothelial cells (HUVECs). Recently, lower concentration thrombin could elicit anti‐inflammatory responses in HUVECs. Here, the effects of lower concentration thrombin on the expression of sPLA2‐IIA in LPS‐stimulated HUVECs were investigated. Prior treatment of cells with thrombin (25–75 pM) inhibited LPS‐induced sPLA2‐IIA expression by activating its receptor, protease‐activated receptor‐1 (PAR‐1). And pretreatment of cells with either PI3‐kinase inhibitor (LY294002) or cholesterol depleting agent (methyl‐β‐cyclodextrin, MβCD) abolished the inhibitory activity of thrombin against sPLA2‐IIA expression. Therefore, these results suggest that PAR‐1 activation by lower concentration thrombin inhibited LPS mediated expression of sPLA2‐IIA by PAR‐1 and PI3‐kinase‐dependent manner in lipid raft on the HUVECs. J. Cell. Biochem. 112: 2502–2507, 2011. © 2011 Wiley‐Liss, Inc.
Impact of HMG‐CoA reductase inhibition on oxidant‐induced injury in human retinal pigment epithelium cells
Authors: Qian Jinqiao , Keyes Kyle T. , Long Bo , Chen Guanglin , Ye Yumei
Published: May 2011

In addition to cholesterol‐lowering effect, HMG‐CoA reductase inhibition by statins has been shown to have protective effect in many cells type. The loss of vision in retinal degeneration disease associates with oxidative stress and apoptosis in retinal pigment epithelium (RPE) cell. This study was designed to examine the effect of statins on oxidant‐induced damage in human RPE cells. Cultured human ARPE‐19 (ARPE) cells were challenged with hydrogen peroxide (H2O2) plus tumor necrosis factor alpha (TNFα) in the presence or absence of statins or various stress signaling inhibitors, including anti‐oxidants N‐acetyl cysteine (NAC), the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI), and the p38 mitogen‐activated protein kinase (p38 MAPK) inhibitor SB203580. Apoptosis was evaluated by TUNEL analysis and cell viability was determined by MTT assay. Reactive oxygen species (ROS) were detected by 2′,7′‐dichlorodihydrofluorescein diacetate (H2DCFH‐DA). Expression of p‐p38 MAPK protein was measured by Western blot analysis. Our findings indicate that statins treatment significantly suppressed oxidant‐induced ROS accumulation and RPE apoptosis. Statins increased cell viability in a dose‐dependent manner. In addition, statins treatment prevented the activation of NADPH oxidase and p38 MAPK signaling induced by oxidative stress. These results suggest that statins protects ARPE cells from oxidative stress via an NADPH oxidase and/or p38 MAPK‐dependent mechanisms, which may contribute to statins‐induced beneficial effects on RPE function. J. Cell. Biochem. 112: 2480–2489, 2011. © 2011 Wiley‐Liss, Inc.