bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of Polymerization Shrinkage Stress and Marginal Microleakage Using Soft‐Start Polymerization
Authors: ERNST CLAUS‐PETER , BRAND NICOLE , FROMMATOR ULRIKE , RIPPIN GERD , WILLERSHAUSEN BRITA
Published: October 2006

Purpose: This study evaluated the influence of a soft‐start light‐curing exposure on polymerization shrinkage stress and marginal integrity of adhesive restorations.

Materials and Methods: Six resin‐based composites (Pertac II, Tetric Ceram, Definite, Surefil, Solitaire, and Visio‐Molar) were adhesively bonded to a cylindrical cavity (n = 9 per material/light) in a photoelastic material. Visible light‐curing was applied using either the standard polymerization mode (800 mW/cm2 exposure duration 40 s) of the curing light (Elipar TriLight, 3M ESPE) or the exponential mode from the same device (ramp‐curing: 150 mW/cm2 to 800 mW/cm2 within the first 15 s of a total curing time of 40 s). Polymerization stress was calculated at 5 minutes, 1 hour, and 24 hours postexposure from the second‐order isochromatic curves obtained from photoelastic images (Matrox‐Inspector). Two standardized Class V preparations were made each on the facial and lingual surfaces of 80 extracted human molars and premolars. Resin restorative systems (Pertac II/EBS Multi, Tetric Ceram/Syntac, Definite/Etch&Prime 3.0, and Surefil/Prime & Bond 2.1) were exposed using both light exposure modes (n = 20). Marginal dye penetration (2% methylene blue) was investigated separately for enamel and cementum margins after thermocycling. To obtain information on equivalent depth of cure, relative surface hardness measurements were performed on resin samples of the same material at the top surface and at 1.5 mm and 3.0 mm thickness (Zwick 3212, 10 N).

Results: A significant (p < .01) reduction in polymerization stress of 7.1% for Pertac II, 4.1% for Tetric Ceram, 3.6% for Definite, 3.7% for Surefil, and 6.2% for Solitaire was observed when using the exponential mode as opposed to the standard. A significant (p = .04) reduction of marginal dye penetration was found only for Pertac II/EBS Multi at the cementum margins when the soft‐start polymerization was used. For the sample thickness of 3 mm, a significant higher relative bottom to top surface ratio in favor of the standard exposure mode was found (p = .001).

CLINICAL SIGNIFICANCE

Depending on the restorative material, soft‐start polymerization may lead to a significant reduction in marginal microleakage of adhesive Class V restorations. This effect might be attributable to a significantly lower polymerization stress, as seen from photoelastic analysis, and/or a decrease in the degree of conversion, as deducted from surface hardness ratios. However, the effect of soft‐start curing mode depends on the material itself, with the most effective response from hybrid resin‐based composites.
Use of a Modified Ovate Pontic in Areas of Ridge Defects: A Report of Two Cases
Authors: LIU CHIUN‐LIN STEVEN
Published: October 2006

A modified design for ovate pontics is proposed to achieve the esthetic, functional, and hygienic requirements for fixed partial dentures. This design should aid the clinician in preparing the edentulous area, thus resulting in less discomfort for the patient because little to no ridge augmentation is required. The same emergence profile can be developed as with the classic ovate pontic design.
Clinical Strategies for Success in Proximoincisal Composite Restorations. Part I: Understanding Color and Composite Selection
Authors: FELIPPE LUÍS ANTÔNIO , Jr SYLVIO MONTEIRO , CALDEIRA DE ANDRADA CESAR ALVES , CERQUEIRA AMANDA DIXON DI , RITTER ANDRE V.
Published: October 2006

The restoration of proximoincisal (Class IV) defects with direct resin‐based composites requires attention to many technical and artistic details. This article is the first of a series of two articles that aim at presenting clinical strategies for optimal success when direct resin‐based composites are used for the restoration of moderate or large proximoincisal defects. Concepts of natural anatomy, color as it relates to dental structures, and composite selection are discussed in this article and are illustrated with a preclinical exercise and two clinical cases in which these concepts are applied.
COMPARISON OF TWO‐ VS. THREE‐VIEW THORACIC RADIOGRAPHIC STUDIES ON CONSPICUITY OF STRUCTURED INTERSTITIAL PATTERNS IN DOGS
Authors: OBER CHRISTOPHER P. , BARBER DON
Published: November 2006

Three‐view thoracic radiography is often used to evaluate patients for pulmonary metastatic disease. Although use of three views has been reported to be more sensitive than two views for focal lung disease, it also requires increased time, effort, and radiographic exposure of patients and personnel. This study was performed to evaluate the conspicuity of lesions on two‐view vs. three‐view radiographic procedures to determine the proportion of diagnoses that would change. One hundred three‐view radiographic studies of the canine thorax were randomized, and four protocols were reviewed for each study: right lateral and ventrodorsal views, left lateral and ventrodorsal views, both lateral views, and all three views. Radiographs were interpreted as either positive or negative for structured interstitial pulmonary disease, and the certainty of the reading was recorded using a visual analog scale. There was 85–88% agreement between each two‐view group and the three‐view group, with the κ statistic ranging from 0.698 to 0.758. There were no differences in certainty of diagnosis among the groups, though within each group there was more certainty for positive diagnoses than negative diagnoses. These findings indicate that three‐view studies should be continued when evaluating for possible structured interstitial pulmonary disease, including metastatic disease, as eliminating one view from a three‐view study would change the diagnosis in 12–15% of patients.
ULTRASONOGRAPHIC FEATURES OF CANINE LIPOMAS
Authors: VOLTA ANTONELLA , BONAZZI MATTIA , GNUDI GIACOMO , GAZZOLA MARGHERITA , BERTONI GIORGIO
Published: November 2006

The purpose of this study was to evaluate the ultrasonographic features of canine lipomas. A group of 94 dogs with a soft tissue mass was considered. All dogs were examined ultrasonographically and cyto/histologic examination was performed. Twenty‐four dogs, whose mass was diagnosed as a lipoma, were selected. Fifty‐five lipomas were present on the 24 dogs. Fifty‐one lipomas were superficial and located subcutaneously. Four lipomas were deep and located in the paratesticular region. Ultrasonographically, lipomas appeared as oval, well‐defined, encapsulated, striated masses.
Defining the Clinical Characteristics of Peyronie’s Disease in Young Men
Authors: Deveci Serkan , Hopps Carin V. , O’Brien Keith , Parker Marilyn , Guhring Patricia , Mulhall John P.
Published: November 2006

Introduction

Peyronie’s disease (PD) is usually seen in men in their fifth decade of life.

Aim

In this study, we investigated the characteristics of the disease in young men.

Main Outcome Measures

The demographics, clinical features, and associated comorbidities of the patients with PD were retrospectively reviewed.

Methods

The findings were compared between men with the disease who were under 40 years of age with those over 40 years. Statistical analyses were conducted to define differentiating features between these two groups.

Results

Of the 296 patients, 32 were under the age of 40 years and 264 over 40 years. The mean duration of the disease was 2 ± 4 and 6 ± 8 months in the respective age groups. Fifty-six percent of the patients under the age of 40 years and 75% of the patients over this age presented with curvature (P < 0.01). Thirty-seven percent under 40 years and 12% men over 40 years had more than one plaque at presentation (P < 0.01). Dupuytren’s contracture was seen only in patients over 40 years of age. Pain at presentation was found in 75% under the age of 40 years and in 65% over 40 years (P = 0.03). Trauma history was found in 18% under 40 years and in 5% over this age (P < 0.01). Statistical significant differences were found between the groups under and over the age of 40 years for hypertension (P < 0.01) and dyslipidemia (P < 0.01). Diabetes was noted in 50% of the patients under the age of 40 years and in 18% of the patients over this age (P < 0.001). Multivariate analysis of conditions associated in men with PD under 40 years of age showed statistical significant differences for diabetes (P = 0.015), presentation within 6 months (P = 0.004), and having multiple plaques (P = 0.008).

Conclusion

Young men with PD are more likely to present at an earlier stage of the disease, to have diabetes, and to have more than one plaque at the time of presentation.
Currents in Contemporary Ethics: Shocking Treatment: The Use of Tasers in Psychiatric Care
Authors: Erwin Cheryl , Philibert Robert
Published: October 2006

The use of restraints on psychiatric patients has long been criticized, and the need for self-restraint of professionals in response to new technologies has been documented from the nineteenth century. Since the middle ages, when leprosy disappeared from civilized society, individuals with a “deranged mind” came to occupy the public space of outcast once reserved for the leper. This diminished social status conflicts with the ethical precept of respect for all patients and the need for humane treatment within the clinical care setting. Psychiatric patients may be presented as a physically dangerous presence in clinical care facilities. New technologies may seem to offer a solution to the problem of balancing the safety of staff with the ethical requirement to treat patients with respect and attention to their medical needs. The Taser, promoted as a safe method of law enforcement, has received notoriety in at least one case involving restraint of psychiatric patients.
plcR papR-Independent Expression of Anthrolysin O byBacillus anthracis
Authors: Ross Caná L. , Koehler Theresa M.
Published: November 2006

Cholesterol-dependent cytolysins (CDCs) are secreted, pore-forming toxins that are associated with pathogenesis in a variety of gram-positive bacteria.Bacillus anthracisproduces anthrolysin O (ALO), a CDC that is largely responsible for the hemolytic activity of culture supernates when the bacterium is cultured in appropriate conditions.B. cereusandB. thuringiensis, species closely related toB. anthracis, produce CDCs with significant amino acid sequence homology to ALO. Transcription of theB. cereusandB. thuringiensisCDC genes is controlled by PlcR, a transcription regulator that requires a pentapeptide derived from thepapRgene product for binding to a consensus sequence (PlcR box) and transcriptional activation of downstream genes. A PlcR box precedes theB. anthracis alogene, and theB. anthracisgenome contains threeplcR-like genes, one of which harbors a nonsense mutation that is predicted to result in a truncated, nonfunctional protein. We detected mRNA ofalo,papR, and the threeplcR-like genes in spleens ofB. anthracis-infected mice, indicating gene expression in vivo. Analysis ofalotranscription in batch culture revealed a potential transcription start located between the PlcR box and the translational start. Nevertheless, steady-state levels ofalotranscripts and ALO protein were unaffected by deletion ofpapRor disruption of the PlcR box. Our data indicate that despite the presence of the transcriptionally activeplcRandpapRgenes inB. anthracisand a PlcR box in the promoter region of thealogene,aloexpression is independent of this control system.
Mutation of His-157 in the Second Pore Loop Drastically Reduces the Activity of the
Synechocystis
Ktr-Type Transporter
Authors: Zulkifli Lalu , Uozumi Nobuyuki
Published: November 2006

Mutation of a conserved His-157 in the second pore loop of KtrB drastically reduced the activity of the K
+
transporter from
Synechocystis
sp. strain PCC 6803. This result suggests that His-157 plays an essential role in the K
+
transport activity of the transporter system.
ExsY and CotY Are Required for the Correct Assembly of the Exosporium and Spore Coat of
Bacillus cereus
Authors: Johnson Matt J. , Todd Sarah J. , Ball David A. , Shepherd Andrew M. , Sylvestre Patricia , Moir Anne
Published: November 2006

The exosporium-defective phenotype of a transposon insertion mutant of
Bacillus cereus
implicated ExsY, a homologue of
B. subtilis
cysteine-rich spore coat proteins CotY and CotZ, in assembly of an intact exosporium. Single and double mutants of
B. cereus
lacking ExsY and its paralogue, CotY, were constructed. The
exsY
mutant spores are not surrounded by an intact exosporium, though they often carry attached exosporium fragments. In contrast, the
cotY
mutant spores have an intact exosporium, although its overall shape is altered. The single mutants show altered, but different, spore coat properties. The
exsY
mutant spore coat is permeable to lysozyme, whereas the
cotY
mutant spores are less resistant to several organic solvents than is the case for the wild type. The
exsY cotY
double-mutant spores lack exosporium and have very thin coats that are permeable to lysozyme and are sensitive to chloroform, toluene, and phenol. These spore coat as well as exosporium defects suggest that ExsY and CotY are important to correct formation of both the exosporium and the spore coat in
B. cereus.
Both ExsY and CotY proteins were detected in Western blots of purified wild-type exosporium, in complexes of high molecular weight, and as monomers. Both
exsY
and
cotY
genes are expressed at late stages of sporulation.
Endothelial dysfunction and decreased vascular responsiveness in the anterior cruciate ligament-deficient model of osteoarthritis
Authors: Miller Daniel , Forrester Kevin , Hart David A. , Leonard Catherine , Salo Paul , Bray Robert C.
Published: November 2006

Chronic inflammation associated with osteoarthritis (OA) may alter normal vascular responses and contribute to joint degradation. Vascular responses to vasoactive mediators were evaluated in the medial collateral ligament (MCL) of the anterior cruciate ligament (ACL)-deficient knee. Chronic joint instability and progressive OA were induced in rabbit knees by surgical transection of the ACL. Under halothane anesthesia, laser speckle perfusion imaging (LSPI) was used to measure MCL blood flow in unoperated control ( n = 12) and 6-wk ACL-transected knees ( n = 12). ACh, bradykinin, histamine, substance P (SP), and prostaglandin E2 (PGE2) were applied to the MCL vasculature in topical boluses of 100 μl (dose range 10−14 to 10−8 mol). In normal joints, ACh, bradykinin, histamine, and PGE2 evoked a dilatory response. Substance P caused a biphasic response that was dilatory from 10−14 to 10−11 mol and constricting at higher doses. In ACL-deficient knees, ACh, bradykinin, histamine, and SP decreased perfusion, whereas PGE2 had a biphasic response that decreased perfusion at 10−14 to 10−11 mol and was dilatory at higher concentrations. Sodium nitroprusside increased perfusion in resting and phenylephrine-precontracted vessels with no significant differences between ACL-transected and control knees. Femoral artery occlusion and release increased perfusion by 74.3 ± 11.1% in control knees but only by 25.8 ± 4.4% in ACL-deficient knees. The altered responsiveness of the MCL vasculature to these inflammatory mediators may indicate endothelial dysfunction in the MCL, which may contribute to the progression and severity of OA and to the adaptation of the joint in an altered mechanical environment.
Long-Term Potentiation (LTP) in the Central Amygdala (CeA) Is Enhanced After Prolonged Withdrawal From Chronic Cocaine and Requires CRF1Receptors
Authors: Fu Yu , Pollandt Sebastian , Liu Jie , Krishnan Balaji , Genzer Kathy , Orozco-Cabal Luis , Gallagher Joel P. , Shinnick-Gallagher Patricia
Published: November 2006

The amygdala is part of the brain reward circuitry that plays a role in cocaine-seeking and abstinence in animals and cocaine craving and relapse in humans. Cocaine-seeking is elicited by cocaine-associated cues, and the basolateral amygdala (BLA) and CeA are essential in forming and communicating drug-related associations that are thought to be critical in long-lasting relapse risk associated with drug addiction. Here we simulated a cue stimulus with high-frequency stimulation (HFS) of the BLA–CeA pathway to examine mechanisms that may contribute to drug-related associations. We found enhanced long-term potentiation (LTP) after 14-day but not 1-day withdrawal from 7-day cocaine treatment mediated through N-methyl-d-aspartate (NMDA) receptors (NRs), L-type voltage-gated calcium channels (L-VGCCs), and corticotropin-releasing factor (CRF)1receptors; this was accompanied by increased phosphorylated NR1 and CRF1protein not associated with changes in NMDA/AMPA ratios in amygdalae from cocaine-treated animals. We suggest that these signaling mechanisms may provide therapeutic targets for the treatment of cocaine cravings.
Nerve-Evoked Synchronous Release and High K+-Induced Quantal Events Are Regulated Separately by Synaptotagmin I at Drosophila Neuromuscular Junctions
Authors: Tamura Takuya , Hou Jiamei , Reist Noreen E. , Kidokoro Yoshiaki
Published: November 2006

The distal Ca2+-binding domain of synaptotagmin I (Syt I), C2B, has two Ca2+-binding sites. To study their function in Drosophila, pairs of aspartates were mutated to asparagines and the mutated syt I was expressed in the syt I–null background ( P[ syt I B-D1,2N] and P[ syt I B-D3,4N]). We examined the effects of these mutations on nerve-evoked synchronous synaptic transmission and high K+-induced quantal events at embryonic neuromuscular junctions. The P[ syt I B-D1,2N] mutation virtually abolished synaptic transmission, whereas the P[ syt I B-D3,4N] mutation strongly reduced but did not abolish it. The quantal content in P[ syt I B-D3,4N] increased with the external Ca2+ concentration, [Ca2+]e, with a slope of 1.86 in double-logarithmic plot, whereas that of control was 2.88. In high K+ solutions the quantal event frequency in P[ syt I B-D3,4N] increased progressively with [Ca2+]e between 0 and 0.15 mM as in control. In contrast, in P[ syt I B-D1,2N] the event frequency did not increase progressively between 0 and 0.15 mM and was significantly lower at 0.15 than at 0.05 mM [Ca2+]e. The P[ syt I B-D1,2N] mutation inhibits high K+-induced quantal release in a narrow range of [Ca2+]e (negative regulatory function). When Sr2+ substituted for Ca2+, nerve-evoked synchronous synaptic transmission was severely depressed and delayed asynchronous release was appreciably increased in control embryos. In high K+ solutions with Sr2+, the quantal event frequency was higher than that in Ca2+ and increased progressively with [Sr2+]e in control and in both mutants. Sr2+ partially substitutes for Ca2+ in synchronous release but does not support the negative regulatory function of Syt I.
Moving equilibria in the public health care sector: A low‐quality trap and a resolution
Authors: Kara Ahmet
Published: November 2006

This paper demonstrates the existence, in a particular subset of the Turkish public health care sector, of equilibria moving towards a low‐quality trap over time. The dynamics of the movement in question hinges, in part, on the socially necessary but demographically asymmetric burden, on some public health care institutions, of providing affordable health care to certain sections of the population. The paper formulates a policy option that could help the sector to escape the trap, moving the sector towards high quality‐high welfare equilibria.
Short Hairpin RNA Knockdown of the Androgen Receptor Attenuates Ligand-Independent Activation and Delays Tumor Progression
Authors: Cheng Helen , Snoek Rob , Ghaidi Fariba , Cox Michael E. , Rennie Paul S.
Published: November 2006

Progression to androgen independence is the lethal end stage of prostate cancer. We used expression of androgen receptor (AR)-targeted short hairpin RNAs (shRNA) to directly test the requirement for AR in ligand-independent activation of androgen-regulated genes and hormone-independent tumor progression. Transient transfection of LNCaP human prostate cancer cells showed that AR shRNA decreased R1881 induction of the prostate-specific antigen (PSA)-luciferase reporter by 96%, whereas activation by forskolin, interleukin-6, or epidermal growth factor was inhibited 48% to 75%. Whereas the antiandrogen bicalutamide provided no further suppression, treatment with the mitogen-activated protein kinase (MAPK) inhibitor U0126 completely abrogated the residual activity, indicating a MAPK-dependent, AR-independent pathway for regulating the PSA promoter. Expression of doxycycline-inducible AR shRNA expression in LNCaP cells resulted in decreased levels of AR and PSA as well as reduced proliferation in vitro. When these cells were grown as xenografts in immunocompromised mice, induction of AR shRNA decreased serum PSA to below castration nadir levels and significantly retarded tumor growth over the entire 55-day experimental period. This is the first demonstration that, by inducibly suppressing AR expression in vivo, there is an extensive delay in progression to androgen independence as well as a dramatic inhibition of tumor growth and decrease in serum PSA, which exceeds that seen with castration alone. Based on these findings, we propose that suppressing AR expression may provide superior therapeutic benefit in reducing tumor growth rate than castration and may additionally be very effective in delaying progression to androgen independence. (Cancer Res 2006; 66(21): 10613-20)
Characterization of GD2 Peptide Mimotope DNA Vaccines Effective against Spontaneous Neuroblastoma Metastases
Authors: Fest Stefan , Huebener Nicole , Weixler Silke , Bleeke Matthias , Zeng Yan , Strandsby Anne , Volkmer-Engert Rudolf , Landgraf Christiane , Gaedicke Gerhard , Riemer Angelika B. , Michalsky Elke , Jaeger Ines S. , Preissner Robert , Förster-Wald Elisabeth , Jensen-Jarolim Erika , Lode Holger N.
Published: November 2006

Disialoganglioside GD2 is an established target for immunotherapy in neuroblastoma. We tested the hypothesis that active immunization against the glycolipid GD2 using DNA vaccines encoding for cyclic GD2-mimicking decapeptides (i.e., GD2 mimotopes) is effective against neuroblastoma. For this purpose, two GD2 peptide mimotopes (MA and MD) were selected based on docking experiments to anti-GD2 antibody ch14.18 (binding free energy: −41.23 kJ/mol for MA and −48.06 kJ/mol for MD) and Biacore analysis (Kd = 12.3 × 10−5 mol/L for MA and 5.3 × 10−5 mol/L for MD), showing a higher affinity of MD over MA. These sequences were selected for DNA vaccine design based on pSecTag2-A (pSA) also including a T-cell helper epitope. GD2 mimicry was shown following transfection of CHO-1 cells with pSA-MA and pSA-MD DNA vaccines, with twice-higher signal intensity for cells expressing MD over MA. Finally, these DNA vaccines were tested for induction of tumor protective immunity in a syngeneic neuroblastoma model following oral DNA vaccine delivery with attenuated Salmonella typhimurium (SL 7207). Only mice receiving the DNA vaccines revealed a reduction of spontaneous liver metastases. The highest anti-GD2 humoral immune response and natural killer cell activation was observed in mice immunized with the pSA-MD, a finding consistent with superior calculated binding free energy, dissociation constant, and GD2 mimicry potential for GD2 mimotope MD over MA. In summary, we show that DNA immunization with pSA-MD may provide a useful strategy for active immunization against neuroblastoma. (Cancer Res 2006; 66(21): 10567-75)
Neurospheres Enriched in Cancer Stem–Like Cells Are Highly Effective in Eliciting a Dendritic Cell–Mediated Immune Response against Malignant Gliomas
Authors: Pellegatta Serena , Poliani Pietro Luigi , Corno Daniela , Menghi Francesca , Ghielmetti Francesco , Suarez-Merino Blanca , Caldera Valentina , Nava Sara , Ravanini Maria , Facchetti Fabio , Bruzzone Maria Grazia , Finocchiaro Gaetano
Published: November 2006

Cancer stem–like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma cells because neurospheres can be enriched in CSC. We obtained murine neurospheres by growing GL261 cells in epidermal growth factor/basic fibroblast growth factor without serum. GL261-NS recapitulated important features of glioblastoma CSC and expressed higher levels of radial glia stem cell markers than GL261 cells growing under standard conditions (GL261 adherent cells, GL261-AC), as assessed by DNA microarray and real-time PCR. GL261-NS brain gliomas were highly infiltrating and more rapidly lethal than GL261-AC, as evidenced by survival analysis (P < 0.0001), magnetic resonance imaging and histology. DC from the bone marrow of syngeneic mice were then used for immunotherapy of GL261-NS and GL261-AC tumors. Strikingly, DC loaded with GL261-NS (DC-NS) cured 80% and 60% of GL261-AC and GL261-NS tumors, respectively (P < 0.0001), whereas DC-AC cured only 50% of GL261-AC tumors (P = 0.0022) and none of the GL261-NS tumors. GL261-NS expressed higher levels of MHC and costimulatory molecules (CD80 and CD86) than GL261-AC; the JAM assay indicated that DC-NS splenocytes had higher lytic activity than DC-AC splenocytes on both GL261-NS and GL261-AC, and immunohistochemistry showed that DC-NS vaccination was associated with robust tumor infiltration by CD8+ and CD4+ T lymphocytes. These findings suggest that DC targeting of CSC provides a higher level of protection against GL261 gliomas, a finding with potential implications for the design of clinical trials based on DC vaccination. (Cancer Res 2006; 66(21): 10247-52)
Interleukin-6 Contributes to Growth in Cholangiocarcinoma Cells by Aberrant Promoter Methylation and Gene Expression
Authors: Wehbe Hania , Henson Roger , Meng Fanyin , Mize-Berge Janna , Patel Tushar
Published: November 2006

The association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. IL-6 can regulate the activity of DNA methyltransferases, and moreover, aberrant DNA methylation can contribute to carcinogenesis. We therefore investigated the effect of chronic exposure to IL-6 on methylation-dependent gene expression and transformed cell growth in human cholangiocarcinoma. The relationship between autocrine IL-6 pathways, DNA methylation, and transformed cell growth was assessed using malignant cholangiocytes stably transfected to overexpress IL-6. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine decreased cell proliferation, growth in soft agar, and methylcytosine content of malignant cholangiocytes. However, this effect was not observed in IL-6-overexpressing cells. IL-6 overexpression resulted in the altered expression and promoter methylation of several genes, including the epidermal growth factor receptor (EGFR). EGFR promoter methylation was decreased and gene and protein expression was increased by IL-6. Thus, epigenetic regulation of gene expression by IL-6 can contribute to tumor progression by altering promoter methylation and gene expression of growth-regulatory pathways, such as those involving EGFR. Moreover, enhanced IL-6 expression may decrease the sensitivity of tumor cells to therapeutic treatments using methylation inhibitors. These observations have important implications for cancer treatment and provide a mechanism by which persistent cytokine stimulation can promote tumor growth. (Cancer Res 2006; 66(21): 10517-24)
Increased Expression of Tissue Transglutaminase in Pancreatic Ductal Adenocarcinoma and Its Implications in Drug Resistance and Metastasis
Authors: Verma Amit , Wang Huamin , Manavathi Bramanandam , Fok Jansina Y. , Mann Aman P. , Kumar Rakesh , Mehta Kapil
Published: November 2006

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases and is virtually incurable. The molecular mechanisms that contribute to the intrinsic resistance of PDAC to various anticancer therapies are not well understood. Recently, we have observed that several drug-resistant and metastatic tumors and tumor cell lines expressed elevated levels of tissue transglutaminase (TG2). Because PDAC exhibits inherent resistance to various drugs, we determined the constitutive expression of TG2 in 75 PDAC and 12 PDAC cell lines. Our results showed that 42 of 75 (56%) PDAC tumor samples expressed higher basal levels of TG2 compared with the normal pancreatic ducts [odds ratio (OR), 2.439; P = 0.012]. The increased expression of TG2 in PDAC was strongly associated with nodal metastasis (OR, 3.400; P = 0.017) and lymphovascular invasion (OR, 3.055; P = 0.045). Increased expression of TG2 was also evident in all 12 cell lines examined. The elevated expression of TG2 in PDAC cell lines was associated with gemcitabine resistance and increased invasive potential. Overexpression of catalytically active or inactive (C277S mutant) TG2 induced focal adhesion kinase (FAK) activation and augmented invasive functions in the BxPC-3 cell line. Conversely, down-regulation of TG2 by small interfering RNA attenuated FAK phosphorylation. Immunoprecipitation and confocal microscopy data revealed that TG2 was associated with FAK protein in PDAC cells. The activated FAK colocalized with TG2 at focal adhesion points. These results show for the first time that elevated expression of TG2 can induce constitutive activation of FAK and thus may contribute to the development of drug resistance and invasive phenotypes in PDAC. (Cancer Res 2006; 66(21): 10525-33)
A Simple Stereotactic Method for Frameless Deep Brain Stimulation
Authors: Eljamel M. Sam , Tulley Mark , Spillane Kate
Published: October 2006

Background: Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease, other movement and psychiatric disorders. DBS implantation requires application of a stereotactic frame throughout a lengthy procedure, making it uncomfortable and tiring. We designed a stereotactic cube to stage the operation, perform frameless microelectrode recording (MER) and fix the DBS. Methods: The 15-mm cube is implanted in a burr hole using bone cement. It contains 5 parallel trajectories (central + 4 around). It is aligned by stereotactic frame so that central trajectory reaches the target. Frameless MER is performed by attaching a micro-driver to the cube using 2–5 cannulae (4 cm). The DBS is fixed to the cube by a mini-plate and 1 screw. Ninety-six cubes were compared with 43 Bennet spheres (BS). Results: No cube moved compared to 2 (5%) BS (p < 0.05). The final trajectory was central in 64.4% of cubes compared to 47.5% of BS, and the final target was >2 mm out in no cubes compared to 12.5% of BS (p < 0.01). Infection and haemorrhage were observed in 2.5% and 3.3% of cubes, respectively, while 5% of BS developed infection, 5% haemorrhage and 7.5% skin erosion. Conclusions: This method is simple and effective in staging DBS procedures, performing frameless MER and DBS implantation, fixation and revision.
Regulation of Wolffian Duct Development
Authors: Hannema Sabine E. , Hughes Ieuan A.
Published: November 2006

Wolffian ducts (WDs) are the embryonic structures that form the male internal genitalia. These ducts develop in both the male and female embryo. However, in the female they subsequently regress, whereas in the male they are stabilised by testosterone. The WDs then develop into separate but contiguous organs, the epididymis, vas deferens and seminal vesicles. Recently, considerable progress has been made in identifying genes that are involved in these different stages of development which is described in this review. In addition, WD development in (atypical forms of) cystic fibrosis and intersex disorders, such as the complete androgen insensitivity syndrome, 17β-hydroxysteroid dehydrogenase deficiency and LH-receptor defects, is discussed. The apparent increase in male reproductive tract disorders is briefly discussed from the perspective of the potential endocrine-disrupting effects of the numerous chemicals in the environment to which the developing male foetus can be exposed.
Buttressing of the Staple Line in Gastrointestinal Anastomoses: Overview of New Technology Designed to Reduce Perioperative Complications
Authors: Yo L.S.F. , Consten E.C.J. , Quarles van Ufford H.M.E. , Gooszen H.G. , Gagner M.
Published: November 2006

Background: Mechanical stapling devices are widely used in all fields of surgery as they can cut and sew tissue in a quick and easy manner. However, complications like bleeding or leakage at the staple line are frequently encountered and can have devastating consequences. Recent developments have led to the introduction of staple line reinforcement to reduce these complications. Methods: The literature has been reviewed to find and describe different methods to improve stapled resections and to give an extensive overview of the different staple line reinforcement materials, their properties and indications. Results: Several types of staple line reinforcement are available. Reinforcement of the staple line with membranes of either non-, semi- or absorbable material seems to be effective in minimizing the risk of leakage and bleeding by providing strength to the cut tissue. Conclusion: Application of staple line reinforcement material seems a promising technique in preventing leakage and bleeding at the stapled suture line, thus potentially reducing complications of gastrointestinal surgery. More studies are needed to investigate the exact properties, behavior and effects of the staple line reinforcement material.
Airway Smooth Muscle Relaxations Induced by Dipyrone
Authors: Gulmez S. Ezgi , Gurdal Hakan , Tulunay F. Cankat
Published: November 2006

Background: Dipyrone differs from other nonsteroidal anti-inflammatory drugs with a distinctive spasmolytic effect; however, the mechanism of action is not clear yet. The possible mechanism behind this effect was investigated on airway smooth muscle tone in vitro. Method:The effect of dipyrone on inositol phosphate (IP) accumulation was evaluated on guinea pig trachea smooth muscle. Changes in intracellular free calcium levels and IP accumulation were evaluated in LTK8 cells.Results: Dipyrone (0.01, 0.1, 1 mmol/l) had a relaxing effect on histamine (0.02 mmol/l)- and adenosine triphosphate- (ATP) (0.01 mol/l)-induced contractions, but not potassium chloride (KCl)-stimulated contractions. This relaxing effect was not observed with in- domethacin. Indomethacin did not inhibit the relaxation response of dipyrone. In isolated tracheal smooth muscle, histamine- (0.02 mmol/l) and ATP (0.01 mmol/l)-induced IP accumulation was significantly inhibited by dipyrone (1 mmol/l). ATP (0.01 mmol/l)-induced IP accumulation was also significantly inhibited by dipyrone (0.01 mmol/l) in LTK8 cells. Dipyrone inhibited ATP-induced (0.01 and 0.1 mmol/l) intracellular calcium increase in LTK8 cells.Conclusion: Inhibition of the release of intracellular Ca2+ may play a role in the smooth muscle relaxing effect of dipyrone. The inhibitor effect of dipyrone on IP accumulation may be due to direct inhibition of phospholipase C (PLC) or impairment of the activation of PLC by G protein-coupled receptor (GPCR).
Mechanisms for Diurnal Variability of Global Tropical Rainfall Observed from TRMM
Authors: Yang Song , Smith Eric A.
Published: October 2006

The behavior and various controls of diurnal variability in tropical–subtropical rainfall are investigated using Tropical Rainfall Measuring Mission (TRMM) precipitation measurements retrieved from the three level-2 TRMM standard profile algorithms for the 1998 annual cycle. Results show that diurnal variability characteristics of precipitation are consistent for all three algorithms, providing assurance that TRMM retrievals are producing consistent estimates of rainfall variability. As anticipated, most ocean areas exhibit more rainfall at night, while over most land areas, rainfall peaks during daytime; however, important exceptions are noted.

The dominant feature of the oceanic diurnal cycle is a rainfall maximum in late-evening–early-morning (LE–EM) hours, while over land the dominant maximum occurs in the mid- to late afternoon (MLA). In conjunction with these maxima are pronounced seasonal variations of the diurnal amplitudes. Amplitude analysis shows that the diurnal pattern and its seasonal evolution are closely related to the rainfall accumulation pattern and its seasonal evolution. In addition, the horizontal distribution of diurnal variability indicates that for oceanic rainfall, there is a secondary MLA maximum coexisting with the LE–EM maximum at latitudes dominated by large-scale convergence and deep convection. Analogously, there is a preponderancy for an LE–EM maximum over land coexisting with the stronger MLA maximum, although it is not evident that this secondary continental feature is closely associated with the large-scale circulation. Neither of the secondary maxima exhibit phase behavior that can be considered semidiurnal in nature. Diurnal rainfall variability over the ocean associated with large-scale convection is clearly an integral component of the general circulation.

Phase analysis reveals differences in regional and seasonal features of the diurnal cycle, indicating that underlying forcing mechanisms differ from place to place. This is underscored by the appearance of secondary ocean maxima in the presence of large-scale convection, along with other important features. Among these, there are clear-cut differences between the diurnal variability of seasonal rainfall over the mid-Pacific and Indian Ocean Basins. The mid-Pacific exhibits double maxima in spring and winter but only LE–EM maxima in summer and autumn, while the Indian Ocean exhibits double maxima in spring and summer and only an LE–EM maximum in autumn and winter. There are also evident daytime maxima within the major large-scale marine stratocumulus regions off the west coasts of continents. The study concludes with a discussion concerning how the observational evidence either supports or repudiates possible forcing mechanisms that have been suggested to explain diurnal rainfall variability.
Diagnosing the Annual Cycle Modes in the Tropical Atlantic Ocean Using a Directly Coupled Atmosphere–Ocean GCM
Authors: DeWitt David G. , Schneider Edwin K.
Published: October 2006

The annual cycle of sea surface temperature (SST) in the tropical Atlantic of a directly coupled atmosphere–ocean general circulation model (CGCM) is decomposed into the parts forced by different surface fluxes (denoted as modes) for the two extreme months of March and August using forced ocean experiments. Almost all previous diagnostic work of the forcing of the SST annual cycle in the Atlantic has concentrated on the near-equatorial region. Here, the annual cycle is examined within the latitude range of 25°S–25°N to facilitate comparison with the interannual variability. The structure of the response to the different surface flux forcings bears some resemblance to the interannual SST modes in the tropical Atlantic, which are diagnosed using rotated empirical orthogonal function (REOF) analysis. Diagnosis of the forcing of the annual cycle modes and the interannual modes shows that they do not always have a common cause. Hence, the simple interpretation that the leading interannual modes are perturbations to the annual cycle is not always valid.

In particular, the equatorial SST annual cycle mode is primarily driven by variations in vertical velocity while the equatorial interannual mode is associated with eastward-propagating thermocline anomalies and is forced by both thermocline anomalies and vertical velocity anomalies. As for the interannual modes, there exist off-equatorial annual cycle modes in both the Northern and Southern Hemispheres. The annual cycle off-equatorial mode in both hemispheres is shown to be primarily driven by heat flux variations. The Southern Hemisphere interannual mode is primarily driven by heat flux variations while the Northern Hemisphere interannual mode shows a strong influence of thermocline depth anomalies. In addition, the Southern Hemisphere interannual mode is centered about 10° south of the annual cycle mode. An interannual mode that has maximum variability along the South American coast south of the equator is shown to be associated with thermocline depth anomalies. This interannual mode has no analog in the annual cycle modes.

The coupled model simulation of the annual cycle is found to be fairly realistic so that the results presented here could have applicability to the observed Atlantic.
“The One Who Did Not Break His Promises”
Authors: Smith Andrea
Published: November 2006

This article examines Native peoples within the race reconciliation movement in evangelical Christianity. Native evangelicals have become increasingly prominent within New Charismatic movements, particularly through the work of the Promise Keepers movement. This presence promotes male dominance, political quietism, and Christian imperialism within Native communities. At the same time, however, Native peoples have used race reconciliation as an opportunity to promote treaty rights and sovereignty struggles within White evangelical communities. Thus, it is unclear if the race reconciliation movement will ultimately push people of color to the Right or White evangelicals to the Left.
The Logic of Practices in Pierre Bourdieu
Authors: Costa Ricardo L.
Published: November 2006

This work proposes a comparative critical approach to the terms in which Pierre Bourdieu formulates, on one hand, the theory of practices and, on the other, those implicit in what he calls ‘public position taking’, a theory of social change. The question that guides the article is: to what degree is the logic of practices contained in the theory of action that the author develops and defends in his scientific works consistent with that enunciated in his public interventions when referring to conditions and mechanisms for change? The analysis leads to a consideration of an important difference between the terms in which Bourdieu analyses and explains social practices, and those he uses when depicting the conditions under which social change is possible.
Genetic-Social Science and the Study of Human Biotechnology
Authors: Owen Tim
Published: November 2006

We require an ontologically flexible, meta-theoretical framework in order to study the ethical implications of genomics and the social construction of the Genome Project. It is argued in this article that a modification of Sibeon's anti-reductionist sociology, which focuses upon agency–structure, micro–macro and time–space, to include a focus upon the biological variable, psychobiography and power would be a ‘starting point’ for a sociology of genomics. The intention is to ‘build bridges’ between sociology and biology, to combine a modified anti-reductionist framework with some of the insights into the sociology–biology divide from the work of Benton, Bury, Hochschild, Layder and Newton for the purpose of conceptualizing the sociological implications of genomics. The term genetic-social science is used to describe the new framework in order to distance it from the association with sociobiology. Such a post-postmodern approach is not reductionist or essentialist. It acknowledges that genes do influence behaviour, yet ‘environment’ is still extremely important.
A Description and Analysis of the German Packaging Take-Back System
Authors: Nakajima Nina , Vanderburg Willem H.
Published: November 2006

The German packaging ordinance is an example of legislated extended producer responsibility (also known as product take-back). Consumers can leave packaging with retailers, and packagers are required to pay for their recycling and disposal. It can be considered to be successful in reducing waste, spurring the redesign of packaging to be more environmentally sustainable, and increasing refilling and recycling. The exception is waste packaging made of plastics, which faces the problems of export due to lack of markets for recycled products within Germany, the lack of capacity for recycling, the allowance for energy recovery within the ordinance, and the manufacturers’ focus on back-to-feedstock rather than back-to-plastics as a solution. This article looks at the ordinance and its effects to consider why this take-back program worked better than others.
Le paradoxe libéral-parétien: un second théorème d'impossibilité dû aux “effets d'indépendance”
Authors: Igersheim Herrade
Published: October 2006

The aim of this article is to take stock of the Sen liberal paradox debate so as to identify a number of approaches to a credible resolution. We demonstrate that, when authors propose solutions to the Pareto-liberal conflict, they ultimately show a marked conceptual preference for one or another condition that in the end weakens the competing condition. We argue that these attempts, none of which is truly satisfactory, reveal the independence effects at the root of the paradox. Explicitly detailed by some, intuited by others, these effects are rarely taken into account globally, for if they were we would then be led to reconsider formalism as a whole, and not merely one condition or another. After Arrow’s, the Pareto-liberal paradox can thus be regarded as a second impossibility theorem, once more affirming the failure of the new welfare economics.
Effect of Interactions between Interface Modifiers and Viscosity Modifiers on the Performance and Processibility of the Rice Hulls-HDPE Composites
Authors: Dixit N. , Kortschot M. T. , Sain M. , Gulati D.
Published: November 2006

Coupling agents are used in wood plastic composites to improve interfacial adhesion between natural fibers and polymers. However, improvement in interfacial adhesion leads to increased melt viscosity, thereby affecting the processing rate. To overcome this limitation, viscosity modifiers are added. Since interface modifiers and viscosity modifiers are chemically active substances, there is a high possibility of interactions between them. To investigate this point, the effect of interactions between viscosity modifiers and an interface modifier on melt flow viscosity and mechanical properties of the composite were analyzed. The results showed that the acrylated maleated polyethylene based interface modifier interacts synergistically with the partially halogenated viscosity modifier, whereas its interaction is antagonistic with the carboxylic acid amide based viscosity modifier.
Use of Methylene Blue in Sepsis: A Systematic Review
Authors: Kwok Edmund S. H. , Howes Daniel
Published: November 2006

A systematic review of the literature was conducted to determine if the administration of methylene blue in humans improves hemodynamic status and/or outcome in patients with septic shock. Studies were identified from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials database. The review included human studies of patients with septic shock treated with methylene blue in which hemodynamic variables or mortality rates were reported. An electronic form was used to extract items including study design, population characteristics, intervention details, and outcomes. No meta-analysis was performed. Methylene blue administration in patients with septic shock increases mean arterial pressure and systemic vascular resistance while decreasing vasopressor requirements. Increased pulmonary vascular resistance has been reported with bolus administration but might be avoided by continuous infusion. No other ill effects were reported. Effects on mortality have not been adequately evaluated in the literature.