bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Oncogenic Activity of the Novel TRIM59 Gene in Mouse Cancer Models
Authors: Valiyeva Fatma , Jiang Fei , Elmaadawi Ahmed , Moussa Madeleine , Yee Siu-Pok , Raptis Leda , Izawa Jonathan I. , Yang Burton B. , Greenberg Norman M. , Wang Fen , Xuan Jim W.
Published: May 2011

A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene–directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue–specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag–mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer. Mol Cancer Ther; 10(7); 1229–40. ©2011 AACR.
Downregulation of Sec23A Protein by miRNA-375 in Prostate Carcinoma
Authors: Szczyrba Jaroslaw , Nolte Elke , Wach Sven , Kremmer Elisabeth , Stöhr Robert , Hartmann Arndt , Wieland Wolf , Wullich Bernd , Grässer Friedrich A.
Published: May 2011

Prostate carcinoma (CaP) is a leading cause of cancer-related death in men. We have previously determined the microRNA (miRNA) profile of primary CaP in comparison with nontumor prostate tissue. miRNAs are small, noncoding RNAs that inhibit protein synthesis on a posttranscriptional level by binding to the 3′-untranslated region (3′-UTR) of their target genes. In primary CaP tissue, we have previously found by miRNA sequencing that miR-375 and miR-200c were upregulated 9.1- and 4.5-fold, respectively. A computational analysis predicted the 3′-UTR of the SEC23A gene as a potential target for both miR-375 and miR-200c. Here, we show that the 3′-UTR of SEC23A mRNA is indeed a target for miR-375 and miR-200c and that both miRNAs downregulate Sec23A protein expression when ectopically expressed in human 293T cells. In primary samples of CaP, we found a direct correlation between reduction of SEC23A mRNA and overexpression of miR-375 but not of miR-200c. The reduced levels of Sec23A protein were inversely correlated to the increased amount of miR-375 in the LNCaP and DU145 CaP cell lines when compared with normal prostate fibroblasts. In primary CaP, we also detected decreased amounts of Sec23A protein when compared with corresponding normal prostate tissue. Ectopically overexpressed Sec23A in LNCaP and DU145 CaP cells significantly reduced the growth properties, indicating that Sec23A might play a role in the induction or growth of prostate carcinoma. Sec23A overexpression reduced cell growth but did not induce apoptosis, whereas inhibition of Sec23A stimulated cell proliferation. Mol Cancer Res; 9(6); 791–800. ©2011 AACR.
Rapamycin Partially Mimics the Anticancer Effects of Calorie Restriction in a Murine Model of Pancreatic Cancer
Authors: Lashinger Laura M. , Malone Lauren M. , Brown Graham W. , Daniels Elizabeth A. , Goldberg Jason A. , Otto Glen , Fischer Susan M. , Hursting Stephen D.
Published: May 2011

Etiologic factors for pancreatic cancer, the 4th deadliest malignant neoplasm in the United States, include obesity and abnormal glucose metabolism. Calorie restriction (CR) and rapamycin each affect energy metabolism and cell survival pathways via inhibition of mammalian target of rapamycin (mTOR) signaling. By using a Panc02 murine pancreatic cancer cell transplant model in 45 male C57BL/6 mice, we tested the hypothesis that rapamycin mimics the effects of CR on pancreatic tumor growth. A chronic regimen of CR, relative to an ad libitum-fed control diet, produced global metabolic effects such as reduced body weight (20.6 ± 1.6 g vs. 29.3 ± 2.3 g; P < 0.0001), improved glucose responsiveness, and decreased circulating levels of insulin-like growth factor (IGF)-1 (126 ± 8 ng/mL vs. 199 ± 11 ng/mL; P = 0.0006) and leptin (1.14 ± 0.2 ng/mL vs. 5.05 ± 1.2 ng/mL; P = 0.01). In contrast, rapamycin treatment (2.5 mg/kg intraperitoneal every other day, initiated in mice following 20 weeks of ad libitum control diet consumption), relative to control diet, produced no significant change in body weight, IGF-1 or leptin levels, but decreased glucose responsiveness. Pancreatic tumor volume was significantly reduced in the CR group (221 ± 107 mm3; P < 0.001) and, to a lesser extent, the rapamycin group (374 ± 206 mm3; P = 0.04) relative to controls (550 ± 147 mm3), and this differential inhibition correlated with expression of the proliferation marker Ki-67. Both CR and rapamycin decreased phosphorylation of mTOR, p70/S6K, and S6 ribosomal protein, but only CR decreased phosphorylation of Akt, GSK-3β, extracellular signal regulated kinase/mitogen-activated protein kinase, and STAT3TYR705. These findings suggest that rapamycin partially mimics the anticancer effects of CR on tumor growth in a murine model of pancreatic cancer. Cancer Prev Res; 4(7); 1041–51. ©2011 AACR.
Genetic Reduction of Insulin-like Growth Factor-1 Mimics the Anticancer Effects of Calorie Restriction on Cyclooxygenase-2–Driven Pancreatic Neoplasia
Authors: Lashinger Laura M. , Malone Lauren M. , McArthur Mark J. , Goldberg Jason A. , Daniels Elizabeth A. , Pavone Amy , Colby Jennifer K. , Smith Nicole C. , Perkins Susan N. , Fischer Susan M. , Hursting Stephen D.
Published: May 2011

Risk of pancreatic cancer, the fourth deadliest cancer in the United States, is increased by obesity. Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of IGF-1. In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 levels and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing COX-2 [bovine keratin-5 promoter (BK5.COX-2)]. These findings in CR mice correlated with reductions in Ki-67–positive cells, vascular luminal size, VEGF expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. Cell lines derived from BK5.COX-2 ductal lesions (JC101 cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1–deficient (LID) mice. The approximate 65% reduction of serum IGF-1 levels in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. These data show that CR prevents development of dysplasia and growth of pancreatic cancer through alterations in IGF-1, suggesting that modulation of this pathway with dietary and/or pharmacologic interventions is a promising pancreatic cancer prevention strategy. Cancer Prev Res; 4(7); 1030–40. ©2011 AACR.
Safety of Parecoxib in Asthmatic Patients with Aspirin-Exacerbated Respiratory Disease
Authors: Valero Antonio , Sánchez-López Jaime , Bartra Joan , Serrano Carlos , Muñoz-Cano Rosa , Roca Jordi , Picado Cesar
Published: May 2011

Background: Aspirin-exacerbated respiratory disease (AERD) affects a subset of patients with asthma. Cyclooxygenase 2 inhibitors are a safe alternative in patients with AERD. Parecoxib is the first cyclooxygenase 2 selective drug for parenteral administration, especially useful after surgery thanks to its analgesic power. The aim of the study is to assess the tolerance of parecoxib (Dynastat®; Pfizer) given by intramuscular route in patients with AERD. Methods: Patients evaluated were referred to the Pneumology and Respiratory Allergy Department of the Hospital Clinic (Barcelona, Spain) for asthma exacerbations precipitated by 2 or more different non-steroidal anti-inflammatory drugs (NSAIDs). AERD was confirmed by a nasal challenge test with aspirin. Patients were challenged with parecoxib, and urine samples were collected to measure the leukotriene E4 concentration. Results: Ten patients were challenged with parecoxib. No symptoms were reported with any of the administered doses, and there were no signs of immediate or delayed hypersensitivity. There were no alterations in the forced expiratory volume in 1 s or in acoustic rhinometry measurements. No significant differences between leukotriene E4 levels were detected. Conclusion: The drug was well tolerated by all patients, with no adverse reactions. This lack of reactions found in our study supports the fact that parecoxib could be a safe alternative in postsurgery analgesia in NSAID-intolerant asthma patients.
Hyaluronidase and Hyaluronan in Insect Venom Allergy
Authors: King Te Piao , Wittkowski Knut M.
Published: May 2011

Background: Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. Methods: HA oligomers (8- to 50-mer; 3–20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300–2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. Results: OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p < 0.05), respectively, for the polymer. Conclusion: Hyaluronidase by its action on HA in skin can function indirectly as adjuvant to promote IgE and IgG1 response in mice. Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people.
Fourier Transform Infrared Imaging Analysis of Cancellous Bone in Alendronate- and Raloxifene-Treated Osteopenic Sheep
Authors: Calton Ericka F. , MacLeay Jennifer , Boskey Adele L.
Published: May 2011

Fourier transform infrared imaging spectroscopy (FTIRI)-assessed bone composition parameters (mineral content, collagen maturity, crystal size and perfection, and carbonate content) describe bone quality and correlate to bone fracture risk. The challenge with studying bone quality in patients treated with antiresorptive drugs such as bisphosphonates (e.g., alendronate) and selective estrogen receptor modulators (SERMs) (e.g. raloxifene) is being able to test bone mechanical performance and material properties pre- and posttreatment. The purpose of this study was to evaluate the FTIRI changes in a large animal model of osteoporosis (female sheep with dietary induced metabolic acidosis; MA). Previous studies have investigated the relationship between bone material properties and bone strength in humans and smaller animals and have shown that changes in compositional properties influence fracture risk. Here we characterize the MA model at 6 and 12 months, demonstrate the loss of bone and changes in compositional properties, and show that 6 months of treatment with both antiresorptives ameliorate the bone loss as assessed by bone mineral density and FTIRI. This preliminary data suggest that the MA sheep model allows investigation of whether drug treatments preserve bone properties that exist at the time of treatment or if they induce further beneficial changes.
Amelogenesis Imperfecta: Genotype-Phenotype Studies in 71 Families
Authors: Wright J. Timothy , Torain Melody , Long Kimberly , Seow Kim , Crawford Peter , Aldred Michael J. , Hart P. Suzanne , Hart Tom C.
Published: May 2011

Amelogenesis imperfecta (AI) represents hereditary conditions affecting the quality and quantity of enamel. Six genes are known to cause AI (AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72). Our aim was to determine the distribution of different gene mutations in a large AI population and evaluate phenotype-genotype relationships. Affected and unaffected family members were evaluated clinically and radiographically by one examiner. Genotyping was completed using genomic DNA obtained from blood or saliva. A total of 494 individuals were enrolled, with 430 (224 affected, 202 unaffected, and 4 not definitive) belonging to 71 families with conditions consistent with the diagnosis of AI. Diverse clinical phenotypes were observed (i.e. hypoplastic, hypocalcified, and hypomaturation). Genotyping revealed mutations in all 6 candidate genes. A molecular diagnosis was made in 132 affected individuals (59%) and in 26 of the families (37%). Mutations involved 12 families with FAM83H (46%), 6 families with AMELX (23%), 3 families with ENAM (11%), 2 families with KLK4 and MMP20 (8% for each gene), and 1 family with a WDR72 mutation (4%). Phenotypic variants were associated with allelic FAM83H and AMELX mutations. Two seemingly unrelated families had the same KLK4 mutation. Families affected with AI where candidate gene mutations were not identified could have mutations not identifiable by traditional gene sequencing (e.g. exon deletion) or they could have promoter sequence mutations not evaluated in this study. However, the results suggest that there remain new AI causative genes to be identified.
Differential Effects of Fibromodulin Deficiency on Mouse Mandibular Bones and Teeth: A Micro-CT Time Course Study
Authors: Goldberg Michel , Marchadier Arnaud , Vidal Catherine , Harichane Yassine , Kamoun-Goldrat Agnès , Kellermann Odile , Kilts Tina , Young Marian
Published: May 2011

Fibromodulin (Fmod) is a keratan sulfate small leucine-rich proteoglycan which is enriched in bones and teeth. In order to determine its functions on bone and tooth mineralization we characterized the phenotype of Fmod-deficient (Fmod-KO) mice using a new-generation microfocus computerized tomography system (micro-CT) and software allowing advanced visualization of 3-D data. Three-week-old and 10- week-old Fmod-KO mandibles and teeth were compared with those of age-matched wild-type (WT) mice. In both young and mature mice the Fmod-KO mandibles were hypomineralized, especially the posterior (proximal) part of the mandible as it appeared to be the main target of the molecule deficiency whereas less extensive alterations were found in the alveolar bone. In transverse sections, larger marrow spaces were observed in the Fmod-KO mice compared with age-matched young or mature WT mice. Quantitative evaluation of the pulp volume of the first molar and 3-D reconstructions suggested that dentinogenesis was diminished in 3-week-old Fmod-KO teeth. In contrast, increased dentin formation was found in 10-week-old Fmod-KO mice and it was accompanied by a reduced pulp volume. Thus, the differential effects of Fmod deficiency on bones and teeth appear to diverge in adult mice. This may result from the previously reported differences in the molecular weight of Fmod in the 2 tissues or from compensatory mechanisms due to the overexpression of DSP and DMP-1 in the dental pulp of Fmod-KO. It is also possible that a single molecule plays diverging roles in a tissue-specific or region-specific manner.
Poorly Ordered Bone as an Endogenous Scaffold for the Deposition of Highly Oriented Lamellar Tissue in Rapidly Growing Ovine Bone
Authors: Kerschnitzki Michael , Wagermaier Wolfgang , Liu Yifei , Roschger Paul , Duda Georg N. , Fratzl Peter
Published: May 2011

The mechanical properties of bone are known to depend on its structure at all length scales. In large animals, such as sheep, cortical bone grows very quickly and it is known that this occurs in 2 stages whereby a poorly ordered (mostly woven) bone structure is initially deposited and later augmented and partially replaced by parallel fibered and lamellar bone with much improved mechanical properties, often called primary osteons. Most interestingly, a similar sequence of events has also recently been observed during callus formation in a sheep osteotomy model. This has prompted the idea that fast intramembranous bone formation requires an intermediate step where bone with a lower degree of collagen orientation is deposited first as a substrate for osteoblasts to coordinate the synthesis of lamellar tissue. Since some osteoblasts become embedded in the mineralizing collagen matrix which they synthesize, the resulting osteocyte network is a direct image of the location of osteoblasts during bone formation. Using 3-dimensional imaging of osteocyte networks as well as tissue characterization by polarized light microscopy and backscattered electron imaging, we revisit the structure of growing plexiform (fibrolamellar) bone and callus in sheep. We show that bone deposited initially is based on osteocytes without spatial correlation and encased in poorly ordered matrix. Bone deposited on top of this has lamellar collagen orientation as well as a layered arrangement of osteocytes, both parallel to the surfaces of the initial tissue. This supports the hypothesis that the initial bone constitutes an endogenous scaffold for the subsequent deposition of parallel fibered and lamellar bone.
Abnormalities in the Enamel in Bmp2-Deficient Mice
Authors: Feng Junsheng , Yang Guobin , Yuan Guohua , Gluhak-Heinrich Jelica , Yang Wuchen , Wang Lynn , Chen Zhi , Schulze McDaniel Jennifer , Donly Kevin J. , Harris Stephen E. , MacDougall Mary , Chen Shuo
Published: May 2011

Tooth development is regulated by epithelial-mesenchymal interactions and their reciprocal molecular signaling. Bone morphogenetic protein 2 (Bmp2) is essential for tooth formation. However, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in the regulation of postnatal enamel formation was investigated via the conditional ablation of Bmp2 in enamel using the (Osx-Cre) mouse. Bmp2 gene ablation was confirmed by PCR analysis in Osx-Cre, Bmp2flox/flox mice. Bmp2-null mice displayed a severe and profound tooth phenotype with asymmetric and open forked incisors. Microradiographs revealed broken incisor tips and dental pulp chamber exposure. The enamel layer of incisors and molars was thin with hypomineralization. Scanning electron microscopy analysis showed that the enamel surface was rough with chipping and the enamel lacked a typical prismatic architecture. These results demonstrate that Bmp2 is essential for enamel formation.
Theoretical Study of Bone Sialoprotein in Bone Biomineralization
Authors: Yang Yang , Mkhonto Donald , Cui Qiang , Sahai Nita
Published: May 2011

Bone sialoprotein (BSP) is an acidic, non-collagenous protein specific to bone proposed previously to promote hydroxyapatite (HAP) nucleation and modulate HAP nanocrystal growth. Specifically, two phosphorylated acidic amino acid sequences in BSP, highly conserved across several vertebrates, are the proposed active sites. We selected one of these sites, i.e. (Sp)2E8, where Sp represents a phosphoserine as a model peptide to study the role of BSP. We used molecular dynamics simulations to determine whether an α-helix or a random coil peptide conformation promotes templated HAP nucleation. A bioinformatics method helps infer preferential crystal growth directions by predicting the likely peptide conformations adsorbed on the (001), (100), and (110) crystal faces of HAP. Results suggest that, independent of conformation, no stable nucleating template is formed and, thus, the ion distributions in the vicinity of the peptide that eventually lead to a stable nucleus start out with disordered arrangements of ions. When adsorbed on all three faces, the Sp residues bind strongly regardless of the peptide conformation, and the Glu residues show different propensities to form helical conformations. The lack of geometrical templating between the peptide residues and all HAP surface sites indicates that adsorption and subsequent crystal growth modulation may be structurally nonspecific.
Differential Enamel and Osteogenic Gene Expression Profiles in Odontogenic Tumors
Authors: Ren C. , Diniz M.G. , Piazza C. , Amm H.M. , Rollins D.L. , Rivera H. , Devilliers P. , Kestler D.P. , Waite P.D. , Mamaeva O.A. , MacDougall M.
Published: May 2011

Odontogenic tumors occur within the jaw bones and may be derived from odontogenic epithelium or ectomesenchyme or contain active components of both tissue types. We investigated the gene expression profile of enamel matrix proteins (EMPs), genes related to osteogenesis, and the mineralization process in odontogenic tumor cell populations focusing on an ameloblastoma (AB-1), a keratocystic odontogenic tumor (KCOT-1), and a calcifying epithelial odontogenic tumor (CEOT-1). All cell populations were shown to be epithelial in origin by CK14 expression. All tested EMPs were expressed by all odontogenic tumor cell types, with higher transcript levels seen in the AB-1 population especially for AMEL, AMBN, and ODAM. CEOT-1 cell populations showed a greater content of ALP-positive cells as well as higher ALP mRNA levels. Using qRT-PCR, we found a higher expression of 8 genes in the CEOT-1 compared to the AB-1 and KCOT-1. In this study we demonstrated the establishment of AB-1, KCOT-1 and CEOT-1 cell populations. The unique gene expression profiles of AB-1, KCOT-1, and CEOT-1 cells and their interactions with the surrounding microenvironment may support their unique tumor development, progression, and survival.
Epigenetic Regulation of Early Osteogenesis and Mineralized Tissue Formation by a HOXA10-PBX1-Associated Complex
Authors: Gordon Jonathan A.R. , Hassan Mohammad Q. , Koss Matthew , Montecino Martin , Selleri Licia , van Wijnen Andre J. , Stein Janet L. , Stein Gary S. , Lian Jane B.
Published: May 2011

Homeodomain-containing (HOX) factors such as the abdominal class homeodomain protein HOXA10 and the TALE-family protein PBX1 form coregulatory complexes and are potent transcriptional and epigenetic regulators of tissue morphogenesis. We have identified that HOXA10 and PBX1 are expressed in osteoprogenitors; however, their role in osteogenesis has not been established. To determine the mechanism of HOXA10-PBX-mediated regulation of osteoblast commitment and the related gene expression, PBX1 or HOX10 were depleted (shRNA or genetic deletion, respectively) or exogenously expressed in C3H10T1/2, bone marrow stromal progenitors, and MC3T3-E1 (preosteoblast) cells. Overexpression of HOXA10 increased the expression of osteoblast-related genes, osteoblast differentiation and mineralization; expression of PBX1 impaired osteogenic commitment of pluripotent cells and the differentiation of osteoblasts. In contrast, the targeted depletion of PBX1 by shRNA increased the expression of bone marker genes (osterix, alkaline phosphatase, BSP, and osteocalcin). Chromatin-associated PBX1 and HOXA10 were present at osteoblast-related gene promoters preceding gene expression, but PBX1 was absent from promoters during the transcription of bone-related genes, including osterix (Osx). Further, PBX1 complexes were associated with histone deacetylases normally linked with chromatin inactivation. Loss of PBX1 but not of HOXA10 from the Osx promoter was associated with increases in the recruitment of histone acetylases (p300), as well as decreased H3K9 methylation, reflecting transcriptional activation. We propose PBX1 plays a central role in attenuating the activity of HOXA10 as an activator of osteoblast-related genes and functions to establish the proper timing of gene expression during osteogenesis, resulting in proper matrix maturation and mineral deposition in differentiated osteoblasts.
Hypoadiponectinemia Is Associated with Valvular Inflammation and Faster Disease Progression in Patients with Aortic Stenosis
Authors: Mohty D. , Pibarot P. , Côté N. , Cartier A. , Audet A. , Després J.P. , Mathieu P.
Published: May 2011

Objectives: Adiponectin is a protein secreted by adipocytes which has anti-inflammatory properties. The objective of this study was to examine the relationship between adiponectinemia and the hemodynamic progression of aortic stenosis (AS) as well as the degree of inflammation in the valve explanted at the time of aortic valve replacement (AVR). Methods: The plasma level of adiponectin was measured in 122 patients undergoing AVR. The explanted aortic valves were analyzed and the density of leukocytes (CD45+), T cells (CD3+) and blood vessels (von Willebrand factor positive; vWF+) was documented. Also, a subset of patients (n = 67) had ≧2 echocardiographic studies separated by at least 6 months, thereby allowing assessment of the rate of progression of stenosis during the preoperative period. Results: Patients with lower plasma levels of adiponectin (<5.4 µg/ml) had a faster progression rate of the mean transvalvular gradient before surgery than those with higher levels (9 ± 1 vs. 4 ±1 mm Hg/year; p = 0.008). Moreover, these patients with hypoadiponectinemia had significantly more leukocytes (CD45+), T cells and blood vessels (vWF+) in their explanted valves compared to those with higher adiponectin levels. Conclusion: These findings support the concept that adiponectin may play a protective role against the inflammatory process and progression of calcific AS.
Health Care Professionals Underestimate the Mean Life Expectancy of Older People
Authors: Wirth R. , Sieber C.C.
Published: May 2011

Background: The estimated life expectancy of older persons is an important component of medical decision-making. To date, no data are available on the accuracy of health care professionals in estimating the remaining life expectancy of older subjects. Methods: A survey estimating the mean remaining life expectancy of Germans of both sexes at the ages of 0, 70, 80 and 90 years was performed from September to November 2010. Results: Two hundred and six health care professionals underestimated the mean remaining life expectancy of older persons by 10%, on average, and with great variance (SD = 34%). Medical doctors, especially those not specialized in geriatrics, estimated worst. Conclusions: Underestimation of the remaining life expectancy of older people is prevalent in health care professionals and may lead to patients being managed inappropriately. This underscores the need for further studies and better training on this issue in health care education.
Prospective Phase II Trial of Gemcitabine in Combination with Irinotecan as First-Line Chemotherapy in Patients with Advanced Biliary Tract Cancer
Authors: Chung Moon Jae , Kim Yoon Jae , Park Jeong Youp , Bang Seungmin , Song Si Young , Chung Jae Bock , Park Seung Woo
Published: May 2011

Background: Chemotherapy is a critical treatment option in advanced biliary tract cancer (BTC), which is often diagnosed at advanced stage and is therefore inoperable. The aim of this phase II trial was to evaluate the efficacy and safety of a combination therapy with gemcitabine and irinotecan as the first-line chemotherapy in patients with previously untreated advanced BTC. Patients and Methods: Patients with pathologically confirmed advanced BTC received gemcitabine (1,000 mg/m2 over 30 min) and irinotecan (100 mg/m2 over 2 h) on days 1 and 8 every 3 weeks. Results: Of 39 patients eligible for this trial, 6 had intrahepatic bile duct cancer, 2 had extrahepatic bile duct cancer and 31 had gallbladder cancer. A total of 193 cycles of chemotherapy were administered, with a median of 4 cycles per patient (range 1–18). The objective response rate was 20.5%, and the disease control rate was 66.7% in intention-to-treat analysis. The median progression-free survival was 4.3 months (95% CI 2.70–5.90), and overall survival was 7.6 months (95% CI 4.56–10.64). Grade 3 and 4 toxicities included anemia (20.5% of patients), thrombocytopenia (2.3%), neutropenia (10.3%), aspartate transaminase increase (10.3%), alanine transaminase increase (5.1%) and emesis (5.1%). Conclusion: Combination therapy of gemcitabine and irinotecan had an efficacy comparable to historic control and can be a viable treatment option. It was well tolerated by patients with advanced BTC.
Changes in the Frequency of Different Categories of Temperature Extremes in India
Authors: Dash S. K. , Mamgain Ashu
Published: May 2011

In the context of climate change and its impact on sectors like agriculture and health, it is important to examine the changes in the characteristics of temperature extremes of different intensities and duration. In this study, an India Meteorological Department gridded temperature dataset is used to examine the changes in the frequency of occurrence of extreme temperatures over India and its seven homogeneous regions during the period 1969–2005. Results indicate a significant decrease in the frequency of occurrence of cold nights in the winter months in India and in its homogeneous regions in the north except in the western Himalaya. Southern regions show a drastic decrease in the frequency of cold nights relative to the period 1969–75. A significant increasing trend in the number of warm days in summer is noticed only in the interior peninsula. In the entire country and on the east coast and west coast, the maximum number of warm days in summer has been noticed only during the last decade, 1996–2005. Further, in the whole country the maximum number of intense warm days and nights in summer has been observed in the last decade. A significant increase in the number of cold days in winter is observed in the north-central and northeast regions. Changes in the frequency of warm and cold exceedances indicate maximum warming in the west coast as compared with all other regions. In sum, such spatial and temporal changes in the characteristics of all categories of temperature extremes broadly suggest warming trends in large parts of India.
Snow Cover and Spring Flood Flow in the Northern Part of Western Siberia (the Poluy, Nadym, Pur, and Taz Rivers)
Authors: Zakharova E. A. , Kouraev A. V. , Biancamaria S. , Kolmakova M. V. , Mognard N. M. , Zemtsov V. A. , Kirpotin S. N. , Decharme B.
Published: May 2011

The paper aims to quantitatively estimate the role of snowmelt in the spring flood flow and the redistribution of river runoff for the northern (Arctic) part of the western Siberian Plain (the rivers Poluy, Nadym, Pur, and Taz). In this region, the presence of wetlands and thermokarst lakes significantly influences the seasonal redistribution of river discharge. First the study region is described, and the snow regime from in situ observations at the Tarko-Sale meteorological station is analyzed. As Special Sensor Microwave Imager (SSM/I) estimates of snow depth for this region are lower than in situ observations, a correction of the SSM/I snow depth estimates is done using snow parameters measured on the snow transect near the meteorological station Tarko-Sale for 1991–96. This reestimated snow depth is then used to assess the volume of water stored every winter on the watersheds for 1989–2006. This snow product is compared with the spring flood streamflow estimated from in situ observations, and the regional relationship between the snow water storage and flood flow is constructed. The proportion of meltwater that does not reach the main rivers and is thus evaporated or stored by the wetlands is estimated to be on average 30% (varying from 0% to 74%). We observe an increasing trend of this value from 20%–30% in the early 1990s to 50%–60% in the mid-2000s. This increase could be attributed to several factors such as increased air temperature (leading to increased evaporation, changes in vegetation cover, and active layer depth) and also to human activity.
Prevalence, Characteristics, and In-Hospital Outcomes of Metabolic Syndrome Among Acute Coronary Syndrome Patients From Oman
Authors: Al-Rasadi Khalid , Sulaiman Kadhim , Panduranga Prashanth , Al-Zakwani Ibrahim
Published: May 2011

We evaluated in-hospital outcomes of acute coronary syndrome (ACS) patients with metabolic syndrome (MetS) in Oman. We analyzed the records of 1392 patients admitted with a diagnosis of ACS as part of the Gulf Registry of Acute Coronary Events. The prevalence of MetS among patients with ACS was 66%, with female preponderance (80% vs 57%; P < .001). MetS was associated with several characteristics including diabetes (45% vs 19%; P < .001), hyperlipidemia (40% vs 23%; P < .001), hypertension (62% vs 34%; P < .001), renal impairment (9.3% vs 3.4%; P < .001), Killip score > II (13% vs 8%; P = .004), and non-ST segment elevation myocardial infarction (78% vs 68%; P < .001). After multivariate adjustment, MetS was associated with higher risk of in-hospital heart failure (odds ratio [OR], 1.37; 95% CI: 1.03-1.81; P = .028) and mortality (OR, 4.42; 95% CI: 1.25-15.5; P = .020). Prevalence of MetS among patients with ACS in Oman is high. MetS was associated with higher in-hospital heart failure and mortality.
Retinal Circulation After Carotid Artery Revascularization
Authors: Cardia Giuseppe , Porfido Domenico , Guerriero Silvana , Loizzi Domenico , Giancipoli Giovanni
Published: May 2011

Doubts still exist concerning the mechanisms involved in ocular ischemic syndrome (OIS) and its dependence on carotid disease. We report findings from 14 surgical patients undergoing carotid artery reconstruction for symptomatic cerebrovascular disease. All of them had fluorescein angiography (FA) of the eye ipsilateral to the carotid operation before surgery and 3 months after to provide information regarding retinal circulation time. Before the surgical procedure, the mean circulation time was 29.4 ± 9.4 seconds (CI 95%: 24.5-34.3). After 3 months, a significant (P < .001) decrease in the circulation time was observed: 18.9 ± 8.4 seconds (CI 95%: 14.5-23.4). The present series demonstrates that carotid revascularization surgery improved retinal flow in approximately 80% of the patients.
Comparison of Hyperemic Changes in Carotid-Radial Pulse Wave Velocity by Upper and Lower Arm Cuff Occlusion
Authors: Kamran Haroon , Salciccioli Louis , Prudhvi Kalyan , Bastien Carl , Berman Heather , Sharma Abhishek , Lazar Jason M.
Published: May 2011

Carotid-radial pulse wave velocity (PWV) normally decreases following release of upper arm cuff occlusion (hyperemia). Lower arm (LA) elicits less brachial artery dilation than upper arm (UA) occlusion but more closely reflects endothelial function. Using applanation tonometry, we compared changes (Δ) in PWV induced by UA and LA hyperemia in 65 healthy participants. Pulse wave velocity was measured serially. Both techniques decreased PWV maximally at 1 minute with gradual return to baseline by 9 minutes. ΔPWV1min was greater for UA than LA occlusion (-11.5% vs -6.8%, P = .02). Multivariate analysis showed arm location independently related to ΔPWV (P = .036). In participants with variable cardiovascular risk, PWV decline lessened with increasing Framingham risk for both techniques. In conclusion: UA and LA occlusion decrease PWV maximally at 1 minute after release of arterial occlusion. PWV 1 min decline are more marked after UA than LA occlusion and progressively lessens with increasing Framingham risk.
When Gray Matters More Than Black or White
Authors: Williams Rhina Maria Fernandes
Published: May 2011

Although research is scant, there is a growing interest in the manifestation of the racial and cultural context on the schooling of biracial students. The purpose of this qualitative research study was to explore the schooling experiences of 10 Black–White biracial students. Specifically, the goals of the study were to (a) identify the factors Black–White biracial students, ages 16 to 22, perceive as influential in their schooling; and (b) identify the factors the students’ parents perceive as influential in their children’s schooling. This study includes a brief review of the literature related to the schooling experiences of Black–White Biracial students. A qualitative phenomenological methodology was used to guide the design, implementation, and analysis of the study. The findings from the interviews with the biracial youth and their parents resulted in five themes, which were (a) region and school diversity; (b) peers; (c) teachers; (d) curriculum; and (e) socioeconomic status. Implications for researchers, policy makers, and teachers are outlined.
Qualifying Sociopolitical Consciousness
Authors: Dallavis Christian
Published: May 2011

This article explores the intersection of culturally responsive pedagogy and faith-based schooling. The author presents a portion of a larger ethnographic research project conducted at a Catholic elementary school that serves a predominantly Latino population in urban Chicago. This work contributes to theories of culturally responsive education by pointing to tensions that emerge when teachers in faith-based schools seek to foster sociopolitical consciousness, an important tenet of culturally responsive pedagogy. The author proposes the extension of theories of culturally responsive pedagogy to include a form of sociopolitical consciousness that is informed by the religious institutions of the teachers, the students, and the school. By preparing teachers to foster a qualified form of sociopolitical consciousness, school leaders may facilitate the efforts of America’s 325,000 faith-based school teachers to adopt culturally responsive teaching practices in religious school contexts.
Clinical Effectiveness of Orthodontic Miniscrew Implants: a Meta-analysis
Authors: Papadopoulos M.A. , Papageorgiou S.N. , Zogakis I.P.
Published: May 2011

The aim of this meta-analysis was to examine the clinical effectiveness of miniscrew implants (MI) used for anchorage reinforcement compared with that of conventional orthodontic means, as well as to assess the success rates of MIs and the possible risk factors affecting their clinical effectiveness. Literature searches were conducted, and, using specific inclusion and exclusion criteria, two independent investigators performed data extraction and analysis. Overall pooled estimates with 95% confidence intervals (CI) were obtained with the random-effects model. Eight out of 3183 original papers met the inclusion criteria. The mean difference of anchorage loss between the MI and conventional anchorage group was −2.4 mm (95% CI = −2.9 mm to −1.8 mm, p = 0). MIs significantly decreased or negated loss of anchorage. Anchorage loss seemed to be less in the mandible, when the MIs were inserted between the second premolar and the first molar, when 2 MIs were inserted per patient jaw, when they were directly connected, as well as when treatment lasted more than 12 months. MIs presented a success rate of 87.7%, with no significant differences between the various subgroups. However, the results of this meta-analysis should be interpreted with some caution because of the number, quality, and heterogeneity of the included studies.
Alcohol Outlets and Community Levels of Interpersonal Violence
Authors: Pridemore William Alex , Grubesic Tony H.
Published: May 2011

This study examined the association between alcohol outlets and violence. Employing Cincinnati block groups as units of analysis, the authors estimated spatially lagged regression models to determine if the variation in spatial density of alcohol outlets is related to the spatial density of simple and aggravated assaults. The authors estimated separate models for off-premise outlets, bars, and restaurants. The results revealed a positive and significant association between outlet density and assault density. This association held for simple and aggravated assaults and for total outlet density and the density of each type of outlet. Further tests showed the outlet-violence association to be stronger for off-premise outlets relative to bars and restaurants and for simple relative to aggravated assaults. Estimation of attributable fractions (AFs) showed that off-premise outlets may account for approximately one-quarter and one-third of simple and aggravated assaults, respectively.
Deconstructing Ostalgia: The national past between commodity and simulacrum in Wolfgang Becker’s Good Bye Lenin! (2003)
Authors: Godeanu-Kenworthy Oana
Published: May 2011

Using Wolfgang Becker’s film Good Bye Lenin!, this paper analyses the phenomenon of Ostalgia through the lens of Jean Baudrillard’s theories on simulation and simulacra. It argues that Becker’s film deconstructs the nostalgic transformation and commodification of the socialist national past in the post-communist age by exposing the deep collective needs to which this phenomenon responds. Confronted with the ideological dominance of Western ideology after 1989, the characters in the film struggle to render their own past relevant by creating alternative personal and collective narratives hinting at how the core of one’s identity is intrinsically bound to both personal memory and to the collective past that frames this personal memory.
Playing with risk: Balzac, the insurance industry and the creation of fiction
Authors: Tilby Michael
Published: May 2011

In the context of the controversial emergence of insurance companies in France after 1815, and their provision of subject matter for the popular stage and for contemporary visual caricature, this article examines some of the ways in which the fictions comprising Balzac’s Comédie humaine incorporate a response to changing perceptions of risk. The sale of insurance is placed at the heart of L’Illustre Gaudissart (1833), but Balzac was led to allude to insurance, both literally and metaphorically, in a range of other fictional and non-fictional writings. Insurance was promoted by Utopian thinkers, but Balzacian realism, in contrast, issued an ironic challenge to its idealist tenets, thereby developing a new kind of fictional plot that broke with Gothic notions of danger and aligned the novel with radically different notions of catastrophe encouraged by the new socio-economic order.
Effects of Alcohol on the Pharmacokinetics of Morphine Sulfate and Naltrexone Hydrochloride Extended Release Capsules
Authors: Johnson Franklin K. , Ciric Sabrina , Boudriau Sophie , Kisicki James , Stauffer Joseph
Published: May 2011

Although contraindicated, coingestion of alcohol and opioids by patients or drug abusers is a major health concern because of dangerous additive and potentially life‐threatening sedative and respiratory effects. In addition, alcohol has been shown to disrupt the extended‐release characteristics of certain extended‐release opioid formulations, releasing a hazardous amount of opioid over a short time period. Morphine sulfate and naltrexone hydrochloride extended release capsules (MS‐sNT), which contain naltrexone sequestered in each pellet core, are indicated for management of chronic, moderate to severe pain. Sequestered naltrexone is designed for release upon product tampering (crushing) to potentially mitigate morphine‐induced subjective effects. This open‐label, single‐dose, 4‐way crossover, pharmacokinetic drug interaction study compared the relative bioavailability of morphine and naltrexone when MS‐sNT is administered (under fasting conditions) with increasing doses of alcohol. Thirty‐two healthy, opioid‐naive adults were randomized to MS‐sNT administered with 240 mL of 4%, 20%, or 40% alcohol or water. No drug interaction was found between morphine in MS‐sNT and 4% or 20% alcohol. Administration with 40% alcohol did not affect overall morphine exposure but was associated with a 2‐fold increase in Cmax and reduction of tmax from 9 to 4 hours versus MS‐sNT taken with water. Naltrexone sequestering was successful in all treatment arms and not affected by coadministration with alcohol over the dose range tested.
Microdosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1), and Interaction (Grapefruit Juice) Profiles of Celiprolol Following the Oral Microdose and Therapeutic Dose
Authors: Ieiri Ichiro , Doi Yohei , Maeda Kazuya , Sasaki Tomohiro , Kimura Miyuki , Hirota Takeshi , Chiyoda Takeshi , Miyagawa Mayuko , Irie Shin , Iwasaki Kazuhide , Sugiyama Yuichi
Published: May 2011

The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype‐matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 μg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC0–24 of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype‐dependent differences disappeared following the MD. Dose‐normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.
Are You Doing What I’m Doing? Goal Projection in Conversation
Authors: Palomares Nicholas A.
Published: May 2011

The primary focus of the current research is goal projection or the ascription of a perceiver’s own goal onto an interaction partner (i.e., target). Extending the finding that perceivers project their goal onto a target (Kawada, Oettingen, Gollwitzer, & Bargh, 2004), two studies applied a cognitive conceptualization of goal pursuit and detection to explain boundary conditions for goal projection in conversation. Experiment 1 demonstrated that the strength of the cognitive association between perceivers’ goal and the social context moderated projection: Projection was greater for strongly than moderately or weakly linked goals. Experiment 2 established that the target’s goal pursuit efficiency and the congruency between the perceiver’s and the target’s goals influenced projection: Compared with targets’ efficient pursuit of nonidentical goals, projection was greater (a) when the target and perceiver had the same goal regardless of efficiency or (b) when they had different goals but the target was inefficient.