bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐overexpression of p21 and Ki‐67 in head and neck squamous cell carcinoma relative to a significantly poor prognosis
Authors: Fischer Claude A. , Jung Minoa , Zlobec Inti , Green Edith , Storck Claudio , Tornillo Luigi , Lugli Alessandro , Wolfensberger Markus , Terracciano Luigi M.
Published: June 2010

Background.

Head and neck squamous cell carcinomas (HNSCC) are treated by surgery or radiotherapy. Tumor cell death–related markers, such as p21 and Ki‐67, may predict response to therapy and improve treatment choice. We evaluated and compared the effect of their coexpression between patients treated by surgery or radiotherapy.

Methods.

Immunohistochemistry for p21 and Ki‐67 expression in 144 pharyngeal and laryngeal HNSCC samples was analyzed and correlated with follow‐up parameters.

Results.

p21 expression correlated significantly with positive cN classification (p < .001), locoregional relapse (p = .031), and poor overall survival (p = .016), and Ki‐67 positivity with poor survival only (p = .025). Coexpressing tumor phenotypes showed the worst survival (p = .009), observed primarily in patients treated by radiotherapy (p = .077).

Conclusions.

Coexpression of p21/Ki‐67 is a strong negative prognostic factor in HNSCC and could be of particular relevance in tumors treated by primary radiotherapy. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Lectin Complement Pathway Gene Profile of Donor and Recipient Determine the Risk of Bacterial Infections After Orthotopic Liver Transplantation†,‡
Authors: de Rooij Bert-Jan F. , van Hoek Bart , ten Hove Rogier W. , Roos Anja , Bouwman Lee H. , Schaapherder Alexander F. , Porte Robert J. , Daha Mohamed R. , van der Reijden Johan J. , Coenraad Minneke J. , Ringers Jan , Baranski Andrzej G. , Hepkema Bouke G. , Hommes Daniel W. , Verspaget Hein W.
Published: June 2010

Infectious complications after orthotopic liver transplantation (OLT) are a major clinical problem. The lectin pathway of complement activation is liver-derived and a crucial effector of the innate immune defense against pathogens. Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (

MBL2

), the ficolin-2 gene (

FCN2

), and the MBL-associated serine protease gene (

MASP2

) of recipients and donors were determined. Recipients receiving a donor liver in the principal cohort with polymorphisms in all three components i.e.,

MBL2

(XA/O; O/O),

FCN2

+6359T, and

MASP2

+371A, had a cumulative risk of an infection of 75% as compared to 18% with wild-type donor livers (

P

= 0.002), an observation confirmed in the second cohort (

P

= 0.04). In addition, a genetic (mis)match between donor and recipient conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52;

P

= 8.1 × 10−6) and the donor-recipient (mis)match genotype (hazard ratio = 6.41;

P

= 1.9 × 10−7), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and

P

< 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality (

P

= 0.9 × 10−8), of which 80% was infection-related.

Conclusion:

Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT.
Serum Cholesterol and Statin Use Predict Virological Response to Peginterferon and Ribavirin Therapy†,‡
Authors: Harrison Stephen A. , Rossaro Lorenzo , Hu Ke-Qin , Patel Keyur , Tillmann Hans , Dhaliwal Sandeep , Torres Dawn M. , Koury Kenneth , Goteti Venkata S. , Noviello Stephanie , Brass Clifford A. , Albrecht Janice K. , McHutchison John G. , Sulkowski Mark S.
Published: June 2010

Elevated low-density lipoprotein (LDL) levels and statin use have been associated with higher sustained virological response (SVR) rates in patients receiving chronic hepatitis C therapy. However, these relationships have not been well characterized in randomized controlled trials. Furthermore, little is known about the relationship between high-density lipoprotein (HDL) and virological response. To determine whether baseline LDL or HDL levels and statin use affect SVR rates, we retrospectively evaluated the IDEAL (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial, in which 3070 treatment-naive, hepatitis C virus (HCV) genotype 1–infected patients were treated for up to 48 weeks in one of the following arms: (1) peginterferon (PEG-IFN) alfa-2b at 1.5 μg/kg/week with ribavirin (RBV) at 800 to 1400 mg/day, (2) PEG-IFN alfa-2b at 1.0 μg/kg/week with RBV at 800 to 1400 mg/day, or (3) PEG-IFN alfa-2a at 180 μg/week with RBV at 1000 to 1200 mg/day. Virological responses were assessed by pretreatment statin use and baseline elevated LDL levels (≥130 mg/dL) or low HDL levels (<40 mg/dL for men and <50 mg/dL for women). In 1464 patients with baseline elevated LDL levels or low HDL levels, the SVR rate was significantly higher than that in patients with normal levels (44.9% versus 34.0%,

P

< 0.001). In 66 patients receiving a statin pretreatment, the SVR rate was higher than the rate of those not receiving it (53.0% versus 39.3%,

P

= 0.02). In a multivariate logistic regression analysis using the stepwise selection method with baseline characteristics, a high LDL level [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4-1.8,

P

< 0.001], a low HDL level (OR = 0.5, 95% CI = 0.3-0.8,

P

= 0.004), and statin use (OR = 2.0, 95% CI = 1.1-3.7,

P

= 0.02) were independently associated with SVR. Conclusion: Baseline elevated LDL levels or low HDL levels and preemptive statin usage were associated with higher SVR rates. Prospective studies may be considered to explore the biological impact of these factors on HCV RNA replication and treatment response.
Liver Enzymes, Nonalcoholic Fatty Liver Disease, and Incident Cardiovascular Disease: A Narrative Review and Clinical Perspective of Prospective Data†
Authors: Ghouri Nazim , Preiss David , Sattar Naveed
Published: June 2010

In recent years, a strong link has been established between nonalcoholic fatty liver disease (NAFLD) and the pathogenesis of type 2 diabetes mellitus. The potential role of NAFLD in cardiovascular disease (CVD) has also attracted interest. Published studies have tended to use biochemical and imaging surrogate markers of NAFLD, such as elevated gamma glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) and fatty liver on ultrasound, when investigating associations with incident CVD events. Positive associations between both baseline GGT and temporal change in GGT, as well as cardiovascular events and cardiovascular mortality independent of alcohol intake, have been reported in several prospective studies. However, adjustment for confounders is often incomplete, and there is scant evidence of improvement in cardiovascular risk prediction beyond established risk scores when incorporating such data. There also appears to be a strong and underrecognized age interaction, with associations between GGT and incident coronary heart disease (CHD) being strong in young individuals but relatively weak in the elderly. By contrast, ALT appears to be only weakly associated with incident CHD and may exhibit a U-shaped association with total mortality. Finally, although some studies have linked imaging-defined and biopsy-confirmed NAFLD with CVD risk, the evidence is inconsistent, with few incident events and/or insufficient potential confounders.

Conclusion:

A diagnosis of NAFLD is insufficient to consider patients as being at high risk for CVD. The presence of NAFLD should be a clear indication for diabetes screening, but cardiovascular risk screening should be performed with the use of existing risk calculators and should be guided by established cardiovascular risk factors.
Dentate gyrus and hilus transection blocks seizure propagation and granule cell dispersion in a mouse model for mesial temporal lobe epilepsy
Authors: Pallud Johan , Häussler Ute , Langlois Mélanie , Hamelin Sophie , Devaux Bertrand , Deransart Colin , Depaulis Antoine
Published: June 2010

Epilepsy‐associated changes of the anatomical organization of the dentate gyrus and hilus may play a critical role in the initiation and propagation of seizures in mesial temporal lobe epilepsy (MTLE). This study evaluated the role of longitudinal projections in the propagation of hippocampal paroxysmal discharges (HPD) in dorsal hippocampus by performing a selective transection in a mouse model for MTLE obtained by a single unilateral intrahippocampal injection of kainic acid (KA). Full transections of the dentate gyrus and hilus were performed in the transverse axis at 22 days after KA injection when spontaneous HPD were fully developed. They: (i) significantly reduced the occurrence of HPD; (ii) increased their duration at the KA injection site; (iii) abolished their spread along the longitudinal axis of the hippocampal formation and; (iv) limited granule cell dispersion (GCD) of the dentate gyrus posterior to the transection. These data suggest that: (i) longitudinal projections through the dentate gyrus and hilus are involved in HPD spread; (ii) distant hippocampal circuits participate in the generation and cessation of HPD and; (iii) GCD requires continuous HPD to develop, even when seizures are established. Our data reveal a critical role for longitudinal projections in the generation and spread of hippocampal seizures. © 2010 Wiley‐Liss, Inc.
Acute nicotine treatment prevents rem sleep deprivation‐induced learning and memory impairment in rat
Authors: Aleisa A.M. , Helal G. , Alhaider I.A. , Alzoubi K.H. , Srivareerat M. , Tran T.T. , Al‐Rejaie S.S. , Alkadhi K.A.
Published: June 2010

Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long‐term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD‐induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg−1 s.c.) twice a day. In the radial arm water maze (RAWM) task, 24‐ or 48‐h SD significantly impaired learning and short‐term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24‐ and 48‐h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SD‐induced impairment of learning and STM and prevented SD‐induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity. © 2010 Wiley‐Liss, Inc.
Hippocampal granule cells opt for early retirement
Authors: Alme C.B. , Buzzetti R.A. , Marrone D.F. , Leutgeb J.K. , Chawla M.K. , Schaner M.J. , Bohanick J.D. , Khoboko T. , Leutgeb S. , Moser E.I. , Moser M.‐B. , McNaughton B.L. , Barnes C.A.
Published: June 2010

Increased excitability and plasticity of adult‐generated hippocampal granule cells during a critical period suggests that they may “orthogonalize” memories according to time. One version of this “temporal tag” hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90–95%, are effectively “retired.” If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard “orthogonalizer” theory of the role of the dentate gyrus in memory. © 2010 Wiley‐Liss, Inc.
Plasticity of synaptic glun receptors is required for the Src‐dependent induction of long‐term potentiation at CA3‐CA1 synapses
Authors: Li Hong‐Bin , Jackson Michael F. , Yang Kai , Trepanier Catherine , Salter Michael W. , Orser Beverley A. , MacDonald John F.
Published: June 2010

The induction of long‐term potentiation (LTP) of CA3‐CA1 synapses requires activation of postsynaptic N‐methyl‐D‐aspartate receptors (GluNRs). At resting potential, the contribution of GluNRs is limited by their voltage‐dependent block by extracellular Mg2+. High‐frequency afferent stimulation is required to cause sufficient summation of excitatory synaptic potentials (EPSPs) to relieve this block and to permit an influx of Ca2+. It has been assumed that this relief of Mg2+ block is sufficient for induction. We postulated that the induction of LTP also requires a Src‐dependent plasticity of GluNRs. Using whole‐cell recordings, LTP (GluARs) of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors‐EPSCS was induced by pairing postsynaptic depolarization with presynaptic stimulation. This LTP was both GluNR and Src‐dependent, being sensitive to AP‐5, a GluNR selective antagonist, or to SU6656, a Src‐selective inhibitor. When CNQX was used to block all GluARs, we observed a long‐lasting potentiation of GluNR‐mediated EPSCs. This plasticity was prevented by transiently blocking GluNRs during the induction protocol or by chelating intracellular Ca2+. GluNRs plasticity was also prevented by bath applications of SU6656 or intracellular applications of the Src‐selective inhibitory peptide, Src(40–58). It was also blocked by preventing activation of protein kinase C, a kinase that is upstream of Src‐kinase‐dependent regulation of GluNRs. Both GluN2A and GluN2B receptors were found to contribute to the plasticity of GluNRs. The contribution of GluNRs and, in particular, their plasticity to the maintenance of LTP was explored using AP5 and SU6656, respectively. When applied >20 min after induction neither drug influenced the magnitude of LTP. However, when applied immediately after induction, treatment with either drug caused the initial magnitude of LTP to progressively decrease to a sustained phase of reduced amplitude. Collectively, our findings suggest that GluNR plasticity, although not strictly required for induction, is necessary for the maintenance of a nondecrementing component of LTP. © 2010 Wiley‐Liss, Inc.
Minimal driving of hippocampal theta by the supramammillary nucleus during water maze learning
Authors: Ruan Ming , Young Calvin K. , McNaughton Neil
Published: June 2010

Previous studies have shown only modest effects of supramammillary nucleus (SuM) dysfunction on theta frequency and learning in the water maze (WM), with larger effects in other tasks. However, theta recorded from SuM, and used to trigger the production of theta‐like oscillations in the hippocampus, produced reversal of the deficit in WM learning produced by theta blocking. We explored this apparent inconsistency by analyzing the relationship between SuM and hippocampal theta in the control group of this theta‐blocking experiment using coherence, phase analysis, and the directed transfer function. We found little evidence of an influence of SuM on the hippocampus in the bulk of WM learning—with some possibility of SuM becoming involved briefly later in learning. A learning‐related increase in coherence was observed in conjunction with gradual phase reorganization of hippocampal theta in relation to SuM theta. This change in phase dynamics between the two structures was also correlated with a relative increase of the estimated direction of theta propagation from the SuM to the hippocampus. These results are consistent with the previous weak effects of SuM lesions and suggest that the use of SuM as a source to trigger hippocampal theta and recover function is likely to be due to coherence between SuM and some other structure that normally controls hippocampal theta during WM learning. © 2010 Wiley‐Liss, Inc.
Cancer inflammation and regulatory T cells
Authors: Erdman Susan E. , Poutahidis Theofilos
Published: June 2010

Chronic inflammation is essential for cancer growth and metastasis. It follows that factors reducing inflammation would abrogate cancer and restore tissue health. However, roles for anti‐inflammatory CD4+ regulatory cells (TREG) in cancer are enigmatic and controversial. Our recent data reveal that TREG may function in cancer similarly to inflammatory bowel disease or multiple sclerosis, whereby TREG accumulate but lack potency to restore tissue homeostasis under inflammatory conditions. Interestingly, early life exposures to diverse environmental organisms reinforce a protective TREG phenotype that inhibits cancer. In contrast, hygienic individuals with few exposures earlier in life suffer from a dysregulated TREG feedback loop. Consequently, hygienic subjects have increased risk of malignancy later in life. This cancer condition is reversible by blocking underlying inflammation. Taken together, these data help explain increased inflammation‐associated cancer rates in hygienic societies and identify targets to abrogate cancer and restore overall health.
Ethnic and socioeconomic trends in testicular cancer incidence in New Zealand
Authors: Sarfati Diana , Shaw Caroline , Blakely Tony , Atkinson June , Stanley James
Published: June 2010

Ethnic differences in testicular cancer incidence within countries are often sizeable, with white populations consistently having the highest ethnic‐specific rates. Many studies have found that high socioeconomic status is a risk factor for testicular cancer. The objectives of this article are to test whether trends in testicular cancer incidence have varied by ethnicity and socioeconomic position in New Zealand between 1981 and 2004. Five cohorts of the entire New Zealand population for 1981–1986, 1986–1991, 1991–1996, 1996–2001 and 2001–2004 were created, and probabilistically linked to cancer registry records, allowing direct determination of ethnic and household income trends in testicular cancer incidence. There were more than 2,000 cases of testicular cancer over the study period. We found increasing rates of testicular cancer for all ethnic and income groups since 1990s. Maori had higher rates, and Pacific and Asian lower rates than European/other men with rate ratios pooled over time of 1.51 (95% CI 1.31–1.74), 0.40 (95% CI 0.26–0.61) and 0.54 (95% CI 0.31–0.94), respectively. Overall, men with low incomes had higher risk of testicular cancer than those with high incomes (pooled rate ratio for lowest to highest income groups = 1.23; 95% CI 1.05–1.44). There was no strong evidence that disparities in testicular cancer incidence have varied by ethnicity or household income over time. Given the lack of understanding of the etiology of testicular cancer, the unusual patterns identified in the New Zealand context may provide some etiological clues for future novel research.
IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high‐risk Chinese population
Authors: Liu Li , Xu Yan , Liu Zheng , Chen Jianguo , Zhang Yixin , Zhu Jian , Liu Jibin , Liu Sheng , Ji Guozhong , Shi Haibin , Shen Hongbing , Hu Zhibin
Published: June 2010

To investigate the association between the potentially functional polymorphisms in IL12A and IL12B, HBV infection and risk of hepatocellular carcinoma in a Chinese population, we genotyped three polymorphisms, rs568408 (3′UTR G>A), rs2243115 (5′UTR T>G) in IL12A and rs3212227 (3′UTR A>C) in IL12B in a case–control study of 869 hepatocellular carcinoma (HCC) cases and 891 cancer‐free controls. We found that the IL12A rs568408 GA/AA variant genotypes were associated with a significantly increased risk of HCC (adjusted odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.17–2.00), compared with the wild‐type GG homozygote. In the stratified analyses, the increased risk of HCC associated with rs568408 GA/AA was more evident in patients who were negative for HBsAg (adjusted OR = 1.71, 95% CI = 1.23–2.39). However, no significant associations between IL12A rs2243115 T/G, IL12B rs3212227 A/C and risk of HCC were observed. Our findings indicate that IL12A rs568408 may contribute to the risk of HCC and modify HCC risk associated with HBV infection.
Number and Distribution of Superficial Neuromasts in Twelve Common European Cypriniform Fishes and Their Relationship to Habitat Occurrence
Authors: Beckmann Melanie , Erős Tibor , Schmitz Anke , Bleckmann Horst
Published: June 2010

This paper gives the first detailed data on the number and body part related distribution of superficial neuromasts in twelve common European Cypriniform species and examines whether such anatomical variables can be related to rough scale habitat occurrence. The fishes (Barbatula barbatula, Barbus barbus, Chondrostoma nasus, Cobitis taenia, Leuciscus cephalus, Leuciscus leuciscus, Phoxinus phoxinus, Rutilus rutilus, Rhodeus sericeus, Scardinius erythrophthalmus, Tinca tinca, Vimba vimba) were classified in two generalized ‘ecological guilds’, 1) rheophilic and 2) limnophilic or indifferent, based on literature data. The total number of superficial neuromasts was consistent within each species, but differed considerably between species. Lowest numbers of superficial neuromasts were found in Barbatula barbatula (21 ± 4.9 superficial neuromasts per cm body length) (mean ± SD), highest numbers in Vimba vimba (233 ± 36.1). Both species can be classified as rheophilic. Over all no relationship was found between the total number of superficial neuromasts and large scale habitat occurrence. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Do Predators Condition the Distribution of Prey within Micro Habitats? An Experiment with Stoneflies (Plecoptera)
Authors: Bo Tiziano , Fenoglio Stefano , López‐Rodríguez Manuel Jesús , Tierno de Figueroa José Manuel , Grenna Marco , Cucco Marco
Published: June 2010

The selection of habitat by macroinvertebrates living in running waters may be influenced by the physical characteristics of the substratum, as well as by the presence of other species. In this study, an artificial river with three different substrata (pebbles, detritus, and leaves) was utilized to analyze the microhabitat preference of two Plecoptera prey species (Amphinemura sulcicollis and Brachyptera risi), both in absence and in presence of a Plecoptera predator species (Perla marginata). In the absence of predators, both prey species showed a clear preference for the leaf microhabitat. When the predators were present, only Brachyptera risi showed a change of microhabitat selection, with a decrease of leaves and an increase of pebbles and detritus utilization. Amphinemura sulcicollis did not change their substratum utilization. This study demonstrates that the presence of a predator may affect microhabitat selection through a switch from the preferred to the less preferred substrata, although not all species change their habitat utilization in response to predator presence. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Proliferation and mineralization of bone marrow cells cultured on macroporous hydroxyapatite scaffolds functionalized with collagen type I for bone tissue regeneration
Authors: Teixeira S. , Fernandes M. H. , Ferraz M. P. , Monteiro F. J.
Published: June 2010

This study concerns the preparation and in vitro characterization of functionalized hydroxyapatite (HA) porous scaffolds, which are intended to be used as drug‐delivery systems and bone‐regeneration matrices. Hydroxyapatite scaffolds were prepared using the polymer replication method, and, after being submitted to a specific sintering cycle, collagen Type I was incorporated on the surface. After the coating procedure, collagen was crosslinked using the N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride (EDC) and N‐hydroxysuccinimide (NHS) conjugation method. In this study, hydroxyapatite scaffolds with uncrosslinked and crosslinked Type I collagen were evaluated. Cell morphology and deposition of extracellular matrix were assessed by scanning electron microscopy, whereas cell distribution was visualized by means of methylene blue staining. MTS and total DNA quantification assays were used to evaluate the viability and proliferation of human bone marrow cells cultured on all the materials for 28 days. Results showed that the cells were able to adhere, proliferate, and form a mineralized matrix on the surface of all the materials. Furthermore, the cells were able to spread from one pore to another and form cell clusters. The results show that these scaffolds are good candidates to serve as drug delivery vehicles and for tissue engineering purposes. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Dissolution behavior of calcium phosphate nanocrystals deposited on titanium alloy surfaces
Authors: Pezeshki Padina , Lugowski Stanley , Davies John E.
Published: June 2010

We have recently shown that a new implant surface design, achieved by the deposition of discrete nanocrystals of calcium phosphate on microtopographically complex titanium‐based substrates, accelerates osteoconduction and also renders the implant surface bone bonding. Thus, we wished to examine the elution behavior of these calcium phosphate nanocrystals and their modulation in vivo. We first compared the total amount of calcium phosphate on these implants with that of plasma‐sprayed implants, by measuring the eluted calcium using atomic absorption spectrophotometry. We then plotted their dissolution behavior in vitro as a function of pH relevant to physiological conditions. To assess their structural stability in vivo for periods of up to 1 month, we placed samples in diffusion chambers, implanted them in the abdominal cavity of rats, and examined their surfaces by scanning electron microscopy following retrieval. Our results show that these nanocrystals are stable at normal pH but, as expected, dissolve at acidic pH, and that they remain unchanged when exposed to body fluid in vivo for up to 1 month. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Biocompatibility of poly(ethylene glycol)‐based hydrogels in the brain: An analysis of the glial response across space and time
Authors: Bjugstad K. B. , Lampe K. , Kern D. S. , Mahoney M.
Published: June 2010

Poly(ethylene glycol) or PEG‐based hydrogels provide a useful methodology for tissue engineering and the controlled‐release of drugs within the central nervous system (CNS). To be successful, the local neuroinflammatory response to an implant must be well understood. Toward this end, the focus was to examine the localized recruitment and activation of microglia and astrocytes following implantation of PEG‐based hydrogels in the brain. Because they are of clinical relevance and may impact brain tissue differently, hydrogels with different mass loss profiles were examined. At all time points, a needle penetration in sham animals evoked a greater astrocytic response than hydrogel conditions. The astrocyte response that ensued varied with degradation rate. An attenuated response was present in more slowly degrading and nondegrading conditions. Relative to sham, hydrogel conditions attenuated the acute microglial response during the week after implant. By 56 days, microglial levels in shams decreased below the observed response in slowly degrading and nondegradable gels, which remained constant overtime. Although the inflammatory response to PEG‐based hydrogels was complex depending on degradation rates, the magnitude of the acute microglia response and the long‐term astrocyte response were attenuated suggesting the use of these materials for drug and cell delivery to the CNS. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Analysis in vitro of the cytotoxicity of potential implant materials. I: Zirconia‐titania sintered ceramics
Authors: Marchi Juliana , Ussui Valter , Delfino Carina S. , Bressiani Ana H. A. , Marques Márcia M.
Published: June 2010

Zirconia (ZrO2) is a bioinert, strong, and tough ceramic, while titania (TiO2) is bioactive but has poor mechanical properties. It is expected that ZrO2‐TiO2 mixed ceramics incorporate the individual properties of both ceramics, so that this material would exhibit better biological properties. Thus, the objective of this study was to compare the biocompatibility properties of ZrO2‐TiO2 mixed ceramics. Sintered ceramics pellets, obtained from powders of TiO2, ZrO2, and three different ZrO2‐TiO2 mixed oxides were used. Roughnesses, X‐ray diffraction, microstructure through SEM, hardness, and DRIFT characterizations were performed. For biocompatibility analysis cultured FMM1 fibroblasts were plated on the top of disks and counted in SEM micrographs 1 and 2 days later. Data were compared by ANOVA complemented by Tukey's test. All samples presented high densities and similar microstructure. The H2O content in the mixed ceramics was more evident than in pure ceramics. The number of fibroblasts attached to the disks increased significantly independently of the experimental group. The cell growth on the top of the ZrO2‐TiO2 samples was similar and significantly higher than those of TiO2 and ZrO2 samples. Our in vitro experiments showed that the ZrO2‐TiO2 sintered ceramics are biocompatible allowing faster cell growth than pure oxides ceramics. The improvement of hardness is proportional to the ZrO2 content. Thus, the ZrO2‐TiO2 sintered ceramics could be considered as potential implant material. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater , 2010.
Development of a monoclonal antibody that specifically detects tissue inhibitor of metalloproteinase‐4 (TIMP‐4) in formalin‐fixed, paraffin‐embedded human tissues
Authors: Donover P. Scott , Wojciechowski Brian S. , Thirumaran Rajesh , Zemba‐Palko Vlasta , Prendergast George C. , Wallon U. Margaretha
Published: June 2010

Overexpression of the extracellular metalloproteinase inhibitor TIMP‐4 in estrogen receptor‐negative breast cancers was found recently to be associated with a poor prognosis for survival. To pursue exploration of the theranostic applications of TIMP‐4, specific antibodies with favorable properties for immunohistochemical use and other clinical assays are needed. Here we report the characterization of a monoclonal antibody (clone 9:4–7) specific for full‐length human TIMP‐4 with suitable qualities. The antibody was determined to be an IgG2b immunoglobulin. In enzyme‐linked immunosorbent assay (ELISA) and immunoblotting assays, it did not exhibit any detectable crossreactivity with recombinant forms of the other human TIMPs 1, 2, and 3. In contrast, the antibody displayed high specificity and sensitivity for TIMP‐4 including in formalin‐fixed and paraffin‐embedded specimens of human breast specimens. An analysis of tissue microarrays of human cancer and corresponding normal tissues revealed specific staining patterns with excellent signal‐to‐noise ratios. This study documents TIMP‐4 monoclonal antibody clone 9:4–7 as an effective tool for preclinical and clinical investigations. J. Cell. Biochem. 110: 1255–1261, 2010. Published 2010 Wiley‐Liss, Inc.
Cytoplasmic gamma‐tubulin complex from brain contains nonerythroid spectrin
Authors: Thomas Nisha E. , Shashikala Sasidharan , Sengupta Suparna
Published: June 2010

The newer member of the tubulin superfamily, γ‐tubulin, is known to mediate microtubule nucleation from the centrosome of eukaryotic cells with the aid of some other proteins. The major amount of γ‐tubulin is believed to be located in the centrosome before the onset of mitotic division. However, a considerable amount has been found in the cytoplasm in the form of a complex whose function is not well known. Microtubules are most abundant in brain tissues and brain microtubules have been extensively used in many in vitro studies. Thus, it is relevant to use brain tissue to characterize cytoplasmic γ‐tubulin complex. Here we show that cytoplasmic γ‐tubulin in brain tissues exists as a ring complex as in other tissues. Interestingly, along with the common members of the γ‐TuRC reported from several tissues and species, the purified brain cytoplasmic complex contains some high molecular weight proteins including α and β nonerythroid spectrin which are not found in other tissues. Immunohistochemical studies of brain tissue sections also show the co‐localization of γ‐tubulin and spectrin. The possible implications have been discussed. J. Cell. Biochem. 110: 1334–1341, 2010. © 2010 Wiley‐Liss, Inc.
Kaempferol stimulates bone sialoprotein gene transcription and new bone formation
Authors: Yang Li , Takai Hideki , Utsunomiya Tadahiko , Li Xinyue , Li Zhengyang , Wang Zhitao , Wang Shuang , Sasaki Yoko , Yamamoto Hirotsugu , Ogata Yorimasa
Published: June 2010

Kaempferol is a typical flavonol‐type flavonoid that is present in a variety of vegetables and fruits, and has a protective effect on postmenopausal bone loss. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone and could be crucial for osteoblast differentiation, bone matrix mineralization and tumor metastasis. In the present study we investigated the regulation of BSP transcription by kaempferol in rat osteoblast‐like UMR106 cells, and the effect of kaempferol on new bone formation. Kaempferol (5 µM) increased BSP and Osterix mRNA levels at 12 h and up‐regulated Runx2 mRNA expression at 6 h. Kaempferol increased luciferase activity of the construct pLUC3, which including the promoter sequence between nucleotides −116 to +60. Transcriptional stimulation by kaempferol abrogated in constructs included 2 bp mutations in the inverted CCAAT, CRE, and FRE elements. Gel shift analyses showed that kaempferol increased nuclear protein binding to CRE and FRE elements, whereas the CCAAT‐protein complex did not change after kaempferol stimulation. Twelve daily injections of 5 µM kaempferol directly into the periosteum of parietal bones of newborn rats increased new bone formation. These data suggest that kaempferol increased BSP gene transcription mediated through inverted CCAAT, CRE, and FRE elements in the rat BSP gene promoter, and could induce osteoblast activities in the early stage of bone formation. J. Cell. Biochem. 110: 1342–1355, 2010. © 2010 Wiley‐Liss, Inc.
Mitotic drug targets
Authors: Kaestner Phillip , Bastians Holger
Published: June 2010

Mitosis is the key event of the cell cycle during which the sister chromatids are segregated onto two daughter cells. It is well established that abrogation of the normal mitotic progression is a highly efficient concept for anti‐cancer treatment. In fact, various drugs that target microtubules and thus interfere with the function of the mitotic spindle are in clinical use for the treatment of various human malignancies for many years. However, since microtubule inhibitors not only target proliferating cells severe side effects limit their use. Therefore, the identification of novel mitotic drug targets other than microtubules have gained recently much attention. This review will summarize the latest developments on the identification and clinical evaluation of novel mitotic drug targets and will introduce novel concepts for chemotherapy that are based on recent progress in our understanding how mitotic progression is regulated and how anti‐mitotic drugs induce tumor cell death. J. Cell. Biochem. 111: 258–265, 2010. © 2010 Wiley‐Liss, Inc.
Reciprocal Relationship Between Cytosolic NADH and ENOX2 Inhibition Triggers Sphingolipid‐Induced Apoptosis in HeLa Cells
Authors: De Luca Thomas , Morré Dorothy M. , Morré D. James
Published: June 2010

ENOX2 (tNOX), a tumor‐associated cell surface ubiquinol (NADH) oxidase, functions as an alternative terminal oxidase for plasma membrane electron transport. Ubiquitous in all cancer cell lines studied thus far, ENOX2 expression correlates with the abnormal growth and division associated with the malignant phenotype. ENOX2 has been proposed as the cellular target for various quinone site inhibitors that demonstrate anticancer activity such as the green tea constituent epigallocatechin‐3‐gallate (EGCg) and the isoflavene phenoxodiol (PXD). Here we present a possible mechanism that explains how these substances result in apoptosis in cancer cells by ENOX2‐mediated alterations of cytosolic amounts of NAD+ and NADH. When ENOX2 is inhibited, plasma membrane electron transport is diminished, and cytosolic NADH accumulates. We show in HeLa cells that NADH levels modulate the activities of two pivotal enzymes of sphingolipid metabolism: sphingosine kinase 1 (SK1) and neutral sphingomyelinase (nSMase). Their respective products sphingosine 1‐phosphate (S1P) and ceramide (Cer) are key determinants of cell fate. S1P promotes cell survival and Cer promotes apoptosis. Using plasma membranes isolated from cervical adenocarcinoma (HeLa) cells as well as purified proteins of both bacterial and human origin, we demonstrate that NADH inhibits SK1 and stimulates nSMase, while NAD+ inhibits nSMase and has no effect on SK1. Additionally, intact HeLa cells treated with ENOX2 inhibitors exhibit an increase in Cer and a decrease in S1P. Treatments that stimulate cytosolic NADH production potentiate the antiproliferative effects of ENOX2 inhibitors while those that attenuate NADH production or stimulate plasma membrane electron transport confer a survival advantage. J. Cell. Biochem. 110: 1504–1511, 2010. © 2010 Wiley‐Liss, Inc.
Pharmacophore alignment search tool: Influence of canonical atom labeling on similarity searching
Authors: Hähnke Volker , Rupp Matthias , Krier Mireille , Rippmann Friedrich , Schneider Gisbert
Published: June 2010

Previously, (Hähnke et al., J Comput Chem 2009, 30, 761) we presented the Pharmacophore Alignment Search Tool (PhAST), a ligand‐based virtual screening technique representing molecules as strings coding pharmacophoric features and comparing them by global pairwise sequence alignment. To guarantee unambiguity during the reduction of two‐dimensional molecular graphs to one‐dimensional strings, PhAST employs a graph canonization step. Here, we present the results of the comparison of 11 different algorithms for graph canonization with respect to their impact on virtual screening. Retrospective screenings of a drug‐like data set were evaluated using the BEDROC metric, which yielded averaged values between 0.4 and 0.14 for the best‐performing and worst‐performing canonization technique. We compared five scoring schemes for the alignments and found preferred combinations of canonization algorithms and scoring functions. Finally, we introduce a performance index that helps prioritize canonization approaches without the need for extensive retrospective evaluation. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Coriolis coupling and nonadiabaticity in chemical reaction dynamics
Authors: Wu Emilia L.
Published: June 2010

The nonadiabatic quantum dynamics and Coriolis coupling effect in chemical reaction have been reviewed, with emphasis on recent progress in using the time‐dependent wave packet approach to study the Coriolis coupling and nonadiabatic effects, which was done by K. L. Han and his group. Several typical chemical reactions, for example, H+D2, F+H2/D2/HD, D++H2, O+H2, and He+H2+, have been discussed. One can find that there is a significant role of Coriolis coupling in reaction dynamics for the ion‐molecule collisions of D++H2, Ne+H, and He+H2+ in both adiabatic and nonadiabatic context. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Depression anxiety stress scale: is it valid for children and adolescents?
Authors: Patrick Jeff , Dyck Murray , Bramston Paul
Published: June 2010

The Depression Anxiety Stress Scale (Lovibond & Lovibond, 1995) is used to assess the severity of symptoms in child and adolescent samples although its validity in these populations has not been demonstrated. The authors assessed the latent structure of the 21‐item version of the scale in samples of 425 and 285 children and adolescents on two occasions, one year apart. On each occasion, parallel analyses suggested that only one component should be extracted, indicating that the test does not differentiate depression, anxiety, and stress in children and adolescents. The results provide additional evidence that adult models of depression do not describe the experience of depression in children and adolescents. © 2010 Wiley Periodicals, Inc. J Clin Psychol: 66:1–12, 2010.
Generation of life events in bipolar spectrum disorders: A re‐examination and extension of the stress generation theory
Authors: Bender Rachel E. , Alloy Lauren B. , Sylvia Louisa G. , Uroševic Snezana , Abramson Lyn Y.
Published: June 2010

The extent to which stress generation occurs in bipolar spectrum disorders (BSD) is not well understood. The present study examined whether 75 BSD participants experienced elevated rates of behavior‐dependent life events, as compared with 38 normal control participants. Within the BSD group, we also examined whether depressive or hypomanic symptoms prospectively predicted increases in various types of negative and positive life events. Results indicated that BSD participants experienced overall increases in behavior‐dependent events over the follow‐up, as compared with normal controls. At the symptom level, the event generation process occurred in more specific event domains. Results suggest that the stress generation theory of unipolar depression can be extended to BSD and that the type of generated events may be polarity‐specific. © 2010 Wiley Periodicals, Inc. J Clin Psychol: 66: 1–20, 2010.
Does the perceived neighborhood reputation contribute to neighborhood differences in social trust and residential wellbeing?
Authors: Kullberg Agneta , Timpka Toomas , Svensson Tommy , Karlsson Nadine , Lindqvist Kent
Published: June 2010

The authors used a mixed methods approach to examine if the reputation of a housing area has bearing on residential wellbeing and social trust in three pairs of socioeconomically contrasting neighborhoods in a Swedish urban municipality. Multilevel logistic regression analyses were performed to examine associations between area reputation and residential wellbeing and social trust, controlling for the random effect of neighborhood and individual level sociodemographic factors. Qualitative data were analyzed to identify mechanisms of how neighborhood reputations were established. The housing area reputation was found to be strongly associated with wellbeing and social trust. The area reputation also seemed to be a determinant of position in the local social structure; residents were found to position themselves in a rank order. The results suggest that area reputation is an important and probably underestimated dimension in the development of residential wellbeing and social trust in housing. © 2010 Wiley Periodicals, Inc.
Community attachment and satisfaction: the role of a community's social network structure
Authors: Crowe Jessica
Published: June 2010

This paper links the micro and macro levels of analysis by examining how different aspects of community sentiment are affected by one's personal ties to the community compared with the organizational network structure of the community. Using data collected from residents of six communities in Washington State, network analysis combined with negative binomial regression is used to determine the effect of personal networks and community networks on community attachment and satisfaction. Findings suggest that while individual‐level variables, such as length of residence and individual ties, affect one's attachment to community, a community's network structure does not significantly affect community attachment. However, a community's network structure significantly affects one's evaluation of community. Regardless of one's ties to the community, residents of cohesive communities are more likely to evaluate the community's social and physical environments more positively. © 2010 Wiley Periodicals, Inc.
PRAS40 acts as a nodal regulator of high glucose‐induced TORC1 activation in glomerular mesangial cell hypertrophy
Authors: Dey Nirmalya , Ghosh‐Choudhury Nandini , Das Falguni , Li Xiaonan , Venkatesan Balachandar , Barnes Jeffrey L. , Kasinath Balakuntalam S. , Ghosh Choudhury Goutam
Published: June 2010

Diabetic nephropathy manifests aberrant activation of TORC1, which senses key signals to modulate protein synthesis and renal hypertrophy. PRAS40 has recently been identified as a raptor‐interacting protein and is a component and a constitutive inhibitor of TORC1. The mechanism by which high glucose stimulates TORC1 activity is not known. PRAS40 was identified in the mesangial cells in renal glomeruli and in tubulointerstitium of rat kidney. Streptozotocin‐induced diabetic renal hypertrophy was associated with phosphorylation of PRAS40 in the cortex and glomeruli. In vitro, high glucose concentration increased PRAS40 phosphorylation in a PI 3 kinase‐ and Akt‐dependent manner, resulting in dissociation of raptor–PRAS40 complex in mesangial cells. High glucose augmented the inactivating and activating phosphorylation of 4EBP‐1 and S6 kinase, respectively, with concomitant induction of protein synthesis and hypertrophy. Expression of TORC1‐nonphosphorylatable mutant of 4EBP‐1 and dominant‐negative S6 kinase significantly inhibited high glucose‐induced protein synthesis and hypertrophy. PRAS40 knockdown mimicked the effect of high glucose on phosphorylation of 4EBP‐1 and S6 kinase, protein synthesis, and hypertrophy. To elucidate the role of PRAS40 phosphorylation, we used phosphorylation‐deficient mutant of PRAS40, which in contrast to PRAS40 knockdown inhibited phosphorylation of 4EBP‐1 and S6 kinase, leading to reduced mesangial cell hypertrophy. Thus, our data identify high glucose‐induced phosphorylation and inactivation of PRAS40 as a central node for mesangial cell hypertrophy in diabetic nephropathy. J. Cell. Physiol. 225: 27–41, 2010. � 2010 Wiley‐Liss, Inc.