bluuebunny/crossref_metadata_2025 huggingface dataset:
Accessory nerve function after level 2b–preserving selective neck dissection
Authors: Celik Bilge , Coskun Hakan , Kumas Ferda F. , Irdesel Jale , Zarifoglu Mehmet , Erisen Levent , Onart Selcuk
Published: April 2009

Background.

The aim of this prospective study was to evaluate the relationship between accessory nerve functions and level 2b–preserving selective neck dissection.

Methods.

Forty‐one necks of 30 patients with laryngeal cancer who underwent unilateral or bilateral level 2b–preserving neck dissections, between February 2003 and July 2005, were evaluated. Neck and shoulder movements and muscle strengths were examined and electroneuromyography (ENMG) was performed preoperatively at the postoperative 21st day and 6th month. Pathological anatomical findings at the postoperative 6th month were also evaluated.

Results.

All shoulder movements and muscle strengths were preserved. Neck extension, rotation movements, and flexion strengths were restricted. ENMG values were affected moderately in the early postoperative period and improved slightly in the late postoperative period. None of the patients developed shoulder syndrome or adhesive capsulitis.

Conclusion.

Preserving level 2b during selective neck dissection decreases trauma to the accessory nerve and improves functional results. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil #
Authors: Ha Nghi B. , Ha Nghiem B. , Garcia Ruel T. , Trinh Huy N. , Vu Andrew A. , Nguyen Huy A. , Nguyen Khanh K. , Levitt Brian S. , Nguyen Mindie H.
Published: April 2009

Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long-term follow-up and data outside of a clinical trial setting. Our goal was to examine the severity and incidence of renal dysfunction in a real-life setting for patients treated with ADV and whose baseline estimated glomerular filtration rate (eGFR) was >50 mL/minute. We performed a cohort study of 290 chronic hepatitis B patients: 145 patients treated with 10 mg ADV and 145 patients unexposed to ADV at two community clinics, who were matched for age (±10 years), sex, and baseline eGFR. The exposed and unexposed populations were well-matched with a similar mean age (46–47 years), proportion of male patients (76.5%), baseline serum creatinine (0.97–0.99 mg/dL), and baseline creatinine clearance (85.0–85.4 mL/minute). The incidence density for renal dysfunction defined by treatment termination and/or development of eGFR ≤50 mL/minute was five cases per 100 patient-years in the exposed group compared with 1.36 cases per 100 patient-years in the unexposed group (P = 0.02). The relative risk of exposed to unexposed was 3.68 (95% confidence interval 1.1–19.3). On Cox proportional hazard analysis also inclusive of sex, ADV was a significant predictor of significant renal dysfunction (hazard ratio [HR] 3.94, P = 0.03). There were also significant trends for age >50 years (HR 3.49, P = 0.087), mild renal impairment at baseline (HR 4.49, P = 0.073), and hypertension and/or diabetes mellitus (HR 2.36, P = 0.074). Conclusion: ADV is an independent predictor for significant deterioration of renal function. Patients on ADV should be monitored, especially patients who are older, have baseline renal insufficiency, or have hypertension and/or diabetes mellitus. (Hepatology 2009.)
Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed # †
Authors: Tripathi Dhiraj , Ferguson James W. , Kochar Narendra , Leithead Joanna A. , Therapondos George , Mcavoy Norma C. , Stanley Adrian J. , Forrest Ewan H. , Hislop William S. , Mills Peter R. , Hayes Peter C.
Published: April 2009

Current therapy for preventing the first variceal bleed includes beta-blocker and variceal band ligation (VBL). VBL has lower bleeding rates, with no differences in survival, whereas beta-blocker therapy can be limited by side effects. Carvedilol, a non-cardioselective vasodilating beta-blocker, is more effective in reducing portal pressure than propranolol; however, there have been no clinical studies assessing the efficacy of carvedilol in primary prophylaxis. The goal of this study was to compare carvedilol and VBL for the prevention of the first variceal bleed in a randomized controlled multicenter trial. One hundred fifty-two cirrhotic patients from five different centers with grade II or larger esophageal varices were randomized to either carvedilol 12.5 mg once daily or VBL performed every 2 weeks until eradication using a multibander device. Seventy-seven patients were randomized to carvedilol and 75 to VBL. Baseline characteristics did not differ between the groups (alcoholic liver disease, 73%; median Child-Pugh score, 8; median age, 54 years; median follow-up, 20 months). On intention-to-treat analysis, carvedilol had lower rates of the first variceal bleed (10% versus 23%; relative hazard 0.41; 95% confidence interval 0.19-0.96 [P = 0.04]), with no significant differences in overall mortality (35% versus 37%, P = 0.71), and bleeding-related mortality (3% versus 1%, P = 0.26). Six patients in the VBL group bled as a result of banding ulcers. Per-protocol analysis revealed no significant differences in the outcomes. Conclusion: Carvedilol is effective in preventing the first variceal bleed. Carvedilol is an option for primary prophylaxis in patients with high-risk esophageal varices. (Hepatology 2009.)
Adipokines in liver diseases #
Authors: Marra Fabio , Bertolani Cristiana
Published: April 2009

Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases. (Hepatology 2009.)
Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice #
Authors: Tchorz Jan S. , Kinter Jochen , Müller Matthias , Tornillo Luigi , Heim Markus H. , Bettler Bernhard
Published: April 2009

Intrahepatic bile duct (IHBD) development begins with the differentiation of hepatoblasts into a single continuous biliary epithelial cell (BEC) layer, called the ductal plate. During ductal plate remodeling, tubular structures arise at distinct sites of the ductal plate, forming bile ducts that dilate into the biliary tree. Alagille syndrome patients, who suffer from bile duct paucity, carry Jagged1 and Notch2 mutations, indicating that Notch2 signaling is important for IHBD development. To clarify the role of Notch2 in BEC differentiation, tubulogenesis, and BEC survival, we developed a mouse model for conditional expression of activated Notch2 in the liver. We show that expression of the intracellular domain of Notch2 (Notch2ICD) differentiates hepatoblasts into BECs, which form additional bile ducts in periportal regions and ectopic ducts in lobular regions. Additional ducts in periportal regions are maintained into adulthood and connect to the biliary tight junction network, resulting in an increased number of bile ducts per portal tract. Remarkably, Notch2ICD-expressing ductal plate remnants were not eliminated during postnatal development, implicating Notch2 signaling in BEC survival. Ectopic ducts in lobular regions did not persist into adulthood, indicating that local signals in the portal environment are important for maintaining bile ducts. Conclusion: Notch2 signaling regulates BEC differentiation, the induction of tubulogenesis during IHBD development, and BEC survival. (Hepatology 2009.)
Fenofibrate differentially regulates plasminogen activator inhibitor-1 gene expression via adenosine monophosphate–activated protein kinase–dependent induction of orphan nuclear receptor small heterodimer partner #
Authors: Chanda Dipanjan , Lee Chul Ho , Kim Yong-Hoon , Noh Jung-Ran , Kim Don-Kyu , Park Ji-Hoon , Hwang Jung Hwan , Lee Mi-Ran , Jeong Kyeong-Hoon , Lee In-Kyu , Kweon Gi Ryang , Shong Minho , Oh Goo-Taeg , Chiang John Y. L. , Choi Hueng-Sik
Published: April 2009

Plasminogen activator inhibitor type I (PAI-1) is a marker of the fibrinolytic system and serves as a possible predictor for hepatic metabolic syndromes. Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is a drug used for treatment of hyperlipidemia. Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of crucial genes involved in various metabolic pathways. In this study, we show that fenofibrate increased SHP gene expression in cultured liver cells and in the normal and diabetic mouse liver by activating the adenosine monophosphate–activated protein kinase (AMPK) signaling pathway in a PPARα-independent manner. Administration of transforming growth factor beta (TGF-β) or a methionine-deficient and choline-deficient (MCD) diet to induce the progressive fibrosing steatohepatitis model in C57BL/6 mice was significantly reversed by fenofibrate via AMPK-mediated induction of SHP gene expression with a dramatic decrease in PAI-1 messenger RNA (mRNA) and protein expression along with other fibrotic marker genes. No reversal was observed in SHP null mice treated with fenofibrate. Treatment with another PPARα agonist, WY14643, showed contrasting effects on these marker gene expressions in wild-type and SHP null mice, demonstrating the specificity of fenofibrate in activating AMPK signaling. Fenofibrate exhibited a differential inhibitory pattern on PAI-1 gene expression depending on the transcription factors inhibited by SHP. Conclusion: By demonstrating that a PPARα-independent fenofibrate-AMPK-SHP regulatory cascade can play a key role in PAI-1 gene down-regulation and reversal of fibrosis, our study suggests that various AMPK activators regulating SHP might provide a novel pharmacologic option in ameliorating hepatic metabolic syndromes. (Hepatology 2009.)
Krüppel‐like factor 12 plays a significant role in poorly differentiated gastric cancer progression
Authors: Nakamura Yu , Migita Toshiro , Hosoda Fumie , Okada Naoko , Gotoh Masahiro , Arai Yasuhito , Fukushima Michiyo , Ohki Misao , Miyata Satoshi , Takeuchi Kengo , Imoto Issei , Katai Hitoshi , Yamaguchi Toshiharu , Inazawa Johji , Hirohashi Setsuo , Ishikawa Yuichi , Shibata Tatsuhiro
Published: April 2009

Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy‐number alterations in 50 primary poorly differentiated gastric cancers using an array‐based comparative genomic hybridization (array‐CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Krüppel‐like factor 12 (KLF12) induced significant growth‐arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ‐521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a significant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures. © 2009 UICC
Population dynamics of serologically identified coinfections with human papillomavirus types 11, 16, 18 and 31 in fertile‐aged Finnish women
Authors: Kaasila Marjo , Koskela Pentti , Kirnbauer Reinhard , Pukkala Eero , Surcel Heljä‐Marja , Lehtinen Matti
Published: April 2009

Licensed human papillomavirus (HPV) vaccines are expected to prevent high‐risk (hr) HPV‐infections (most notably types 16 and 18). Whether HPV vaccination will change the distribution of hrHPVs at the population level is open, since competition between HPV types is not well understood. Two stratified random subcohorts (1983–1997 and 1995–2003) of 7,815 and 3,252 women with a minimum of 2 pregnancies (<32 years) were selected from the Finnish Maternity Cohort. Using ELISA based on virus‐like particles (VLP), we determined antibodies to HPV11, 16, 18 and 31 in paired sera of the women and used Poisson regression models to estimate the risk of further infection with other HPV types in those positive for HPV16 or HPV18 at baseline. Baseline HPV16 seropositivity was associated with increased risk of later infections with HPV18 (3.1, 95% CI: 1.7, 5.6). HPV18 seropositivity was associated with increased risk of HPV16 (3.9, 95% CI: 2.5, 6.1). Our observations favor a coinfection rather than superinfection model for the different HPV types and are not suggestive for type‐replacement following HPV vaccination. © 2009 UICC
The CDH1‐160C>A polymorphism is a risk factor for colorectal cancer
Authors: Pittman Alan M. , Twiss Philip , Broderick Peter , Lubbe Steven , Chandler Ian , Penegar Steven , Houlston Richard S.
Published: April 2009

Part of the inherited susceptibility to colorectal cancer (CRC) is caused by the coinheritance of common low risk variants. E‐cadherin (CDH1) has an established role in CRC; somatic inactivation of CDH1 is a common early event, and germline mutations can cause early‐onset CRC. The ‐160C>A promoter variant (rs16260) of CDH1 has been reported to influence CDH1 transcription and thereby represents a strong candidate for a predisposition locus. To examine this proposition, we conducted a two‐staged association study based on genotyping a total of 5,679 CRC cases and 5,412 controls for rs16260. CDH1‐160C>A genotype was associated with CRC risk (ptrend = 0.001). Compared to common homozygotes, the odds ratios (ORs) of CRC associated with heterozygous and homozygote variant genotype were 0.90 (95% confidence interval [CI]: 0.84–0.97) and 0.81 (95% CI: 0.71–0.93), respectively. In combination with the previously identified 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 risk variants, the risk of CRC increases with an increasing numbers of variant alleles for the 7 loci (ORper allele = 1.16; 95% CI: 1.13–1.19; ptrend = 1.68 × 10−34). These data indicate CDH1‐160C>A is a risk factor for CRC, and because a high proportion of the European population are carriers of at‐risk genotypes, the variant is likely to contribute substantially to the development of CRC. Furthermore, our study underscores the importance of conducting association studies using large sample series to demonstrate polymorphic variants conferring modest relative risks. © 2009 UICC
Epigenetic silencing of argininosuccinate synthetase confers resistance to platinum‐induced cell death but collateral sensitivity to arginine auxotrophy in ovarian cancer
Authors: Nicholson Linda J. , Smith Paul R. , Hiller Louise , Szlosarek Peter W. , Kimberley Christopher , Sehouli Jalid , Koensgen Dominique , Mustea Alexander , Schmid Peter , Crook Tim
Published: April 2009

Evidence indicates that acquired resistance of cancers to chemotherapeutic agents can occurviaepigenetic mechanisms. Down‐regulation of expression of argininosuccinate synthetase (ASS1), the rate‐limiting enzyme in the biosynthesis of arginine, has been associated with the development of platinum resistance in ovarian cancer treated with platinum‐based chemotherapy. The aim of the present study was to analyse epigenetic regulation of ASS1 in ovarian cancer tissue taken at diagnosis and relapse and determine its significance as a predictor of clinical outcome in patients treated with platinum‐based chemotherapy. In addition, expression and epigenetic regulation of ASS1 were analysed in human ovarian cancer cell lines, and ASS1 expression correlated with the ability of the lines to grow in media containing cisplatin, carboplatin or taxol or in arginine‐depleted media. Our results show that aberrant methylation in the ASS1 promoter correlated with transcriptional silencing in ovarian cancer cell lines. ASS1 silencing conferred selective resistance to platinum‐based drugs and conferred arginine auxotrophy and sensitivity to arginine deprivation. In ovarian cancer, ASS1 methylation at diagnosis was associated with significantly reduced overall survival (p= 0.01) and relapse‐free survival (p= 0.01). In patients who relapse, ASS1 methylation was significantly more frequent at relapse (p= 0.008). These data establish epigenetic inactivation of ASS1 as a determinant of response to platinum chemotherapy and imply that transcriptional silencing of ASS1 contributes to treatment failure and clinical relapse in ovarian cancer. The collateral sensitivity of cells lacking endogenous ASS1 to arginine depletion suggests novel therapeutic strategies for the management of relapsed ovarian cancer. © 2009 UICC
Modification of polyurethane to reduce occlusion of enteral feeding tubes
Authors: Gaither Kari A. , Tarasevich Barbara J. , Goheen Steven C.
Published: April 2009

Feeding tubes are used to supply nutritional formula to immobilized patients. The most common cause for failure of enteral feeding tubes is their occlusion. The purpose of this study was to examine whether occlusion of enteral feeding tubes could be minimized using an additive. An open, intermittent enteral feeding system was simulated in the laboratory and data were collected over a period ranging from 2 to 6 days. Feeding formula was cycled through a feeding tube in either the presence or absence of simulated gastric acid in an effort to generate a reproducible occlusion. Pressures in the tube were measured frequently throughout these cycles. We observed pressure spikes with each cycle, but never a complete occlusion. Pressure spikes formed only when simulated gastric acid was mixed with the feeding solution. Large amounts of feeding formula adsorbed onto polyurethane (PU) surfaces in the presence of gastric acid. Also, this subtle change in surface chemistry significantly affected the number of pressure spikes observed. The maximum pressure required to maintain flow in the tube was reduced by about half from 2.0 psi to 0.8 psi when polyvinyl alcohol (PVA) was added. The addition of PVA to PU also reduced the contact angle from 83° (untreated) to ∼64° in the presence of PVA. Furthermore, when formula was added to PU in the presence of PVA the thickness of the layer that remained on the surface was almost 10 times greater in controls than on PVA‐treated surfaces. These results suggest that a treatment that increases the hydrophilicity of the feeding tube may help minimize clogging. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2009
Regeneration of ischemic heart using hyaluronic acid‐based injectable hydrogel
Authors: Yoon So Jeong , Fang Yong Hu , Lim Choon Hak , Kim Bum Shik , Son Ho Sung , Park Yongdoo , Sun Kyung
Published: April 2009

An injectable hydrogel was applied to regenerate a myocardial infarction and functional recovery of the heart. A myocardial infarction was induced in rat by circumflex artery ligation. A hyaluronic acid‐based hydrogel was injected into the epicardium of the infarcted area. Then, cardiac functions and regeneration of the myocardium in sham‐operated (SHAM), myocardial infarction (MI), and gel‐injected group (GEL) (n = 6) were evaluated 4 weeks after the injection. Measurements of the thickness of the wall showed that the thickness in the GEL group increased by up to 200% compared with that in the MI group (p < 0.001). The infarcted area of the left ventricular in the GEL group decreased by 53% compared with the MI group (p < 0.001). The number of arterioles and capillaries in the border zone of the GEL group increased by 152% and 148%, whereas the apoptotic index decreased by 42% (p < 0.05). Measurement of the heart functions, such as ejection fraction, arterial elastance (Ea), dP/dt max, and dP/dt min, indicated that the injection of a hydrogel significantly facilitated the functional recovery compared with the MI group. Because of its simplicity, easy applicability, and a great regenerating potential, this injectable hydrogel promises as a treatment for myocardial infarction. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2009
Use of chitosan membrane associated with polypropylene mesh to prevent peritoneal adhesion in rats
Authors: Paulo Neusa Margarida , de Brito e Silva Marcelo Seixo , Moraes Ângela Maria , Rodrigues Ana Paula , de Menezes Liliana Borges , Miguel Marina Pacheco , de Lima Flávia Gontijo , de Morais Faria Aline , Lima Lívia Maria Lindoso
Published: April 2009

The correction of wall abdominal defects often requires the use of implants such as polypropylene meshes. In spite of presenting good tissue acceptance, these biomaterials can migrate to adjacent viscera, promote enterocutaneos fistulas, tissue adherence and visceral erosions. In this work, the barrier effect of chitosan films associated with polypropylene meshes on adhesion formation experimentally induced in Wistar rats was evaluated. The animals were divided into two groups with 10 animals each. Animals in the CPP group were implanted with chitosan films associated with polypropylene meshes, whereas the ones in the PP group received only polypropylene meshes. After 8 days, the animals were submitted to euthanasia using CO2 and a descriptive study focusing adhesion formation, visceral involvement with sutures and mesh peritonization was performed. Also, subimplanted material was collected for histopathology analysis. The results showed that the CPP group presented weak adhesions to the omentum over the stitch knots in eight animals. In all animals, the meshes were peritonized, not allowing their visualization after removing the chitosan films. In the PP group, six animals presented intestinal adhesions to the meshes and, in one of them, hepatic adhesion to the mesh was observed, besides omentum adhesion on more than 50% of the mesh area. The protective effect of chitosan films when sutured over polypropylene meshes, as well as no exacerbation of inflammation associated to the peritoneal lesions was statistically demonstrated. Therefore, chitosan films can indeed minimize the formation of peritoneal adhesions induced by polypropylene meshes in rats. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2009
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Authors: Morris Garrett M. , Huey Ruth , Lindstrom William , Sanner Michel F. , Belew Richard K. , Goodsell David S. , Olson Arthur J.
Published: April 2009

We describe the testing and release of AutoDock4 and the accompanying graphical user interface AutoDockTools. AutoDock4 incorporates limited flexibility in the receptor. Several tests are reported here, including a redocking experiment with 188 diverse ligand‐protein complexes and a cross‐docking experiment using flexible sidechains in 87 HIV protease complexes. We also report its utility in analysis of covalently bound ligands, using both a grid‐based docking method and a modification of the flexible sidechain technique. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
DFT study of the carbon‐ and nitrogen‐pivot lariat crown ethers and their complexes with alkali metal cations: Na+, K+
Authors: Zheng Xiaoyan , Wang Xueye , Yi Shanfeng , Wang Nuanqing , Peng Yueming
Published: April 2009

In this work, a quantum mechanical research of five lariat crown ethers(LCEs), 2‐methoxy‐15‐crown‐5(A), N‐methoxy‐4‐aza‐15‐crown‐5(B), N‐methoxy‐4‐aza‐18‐crown‐6(C), N‐methoxyethyl‐4‐aza‐18‐crown‐6(D), N,N′‐bis(2‐metho xyethyl)‐4,13‐diaza‐18‐crown‐6(E), which are based on either 15‐crown‐5 or 18‐crown‐6 frameworks and contain various pendant arms extending from either carbon or nitrogen atoms on the crown frameworks, had been done using density functional theory with B3LYP/6‐31G* method to obtain the electronic and geometrical structures of the LCEs and their complexes with alkali metal ions: Na+ and K+. The nucleophilicity of LCEs had been investigated by the Fukui functions. For complexes, the match between the cation and cavity size, the status of interaction between alkali metal ions and donor atoms in the LCEs, and the sidearm effect of the LCEs had been analyzed through the other calculated parameters, such as, highest occupied molecular orbital energy, lowest unoccupied molecular orbital energy, and energy gaps. In addition, the enthalpies of complexation reaction had been studied by the calculated thermodynamic data (298 K). The calculated results are all in a good agreement with the experimental data for the complexes. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
QSAR of antilipid peroxidative activity of substituted benzodioxoles using chemometric tools
Authors: Mitra Indrani , Roy Kunal , Saha Achintya
Published: April 2009

Search and development of new effective antioxidant molecules with improved activity is of both biological and commercial importance. In this background, we have modeled antioxidant activities of a series of benzodioxoles for their ability to inhibit lipid peroxidation (pC) using quantitative structure activity relationship (QSAR) technique. The QSAR models were developed using different chemometric tools such as GFA and G/PLS techniques. Two different sets of descriptors were used for developing these QSAR models. Molecular shape analysis (MSA) and spatial (charged partial surface area and shadow) descriptors were included in the one set, whereas quantum chemical (Mulliken charges on common atoms of the molecules calculated at the AM1 level) and physicochemical (hydrophobic parameter and molar refractivity) descriptors were included in the other set. All the models developed were validated internally by leave‐one‐out cross‐validation and randomization techniques. The model predictivity was judged by their cross‐validated squared correlation coefficient (Q2) and the modified r2 (r) values, whereas the robustness of the models was judged from the value of R (Roy and Paul, QSAR Comb Sci DOI:10.1002/qsar.200810130). The developed models suggest that the antilipid peroxidative activity of the molecules largely depends on the charges of the carbon atoms connected to the oxygen atoms of the dioxole ring. Besides this, the activity also depends on the charged surface area of the molecules and the dipole moment of the molecules. Presence of the methoxy substituents (ortho or meta) on the phenyl ring at the R1 position of the benzodioxoles significantly lowers the antioxidant activity of these molecules. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
Geometric similarity between protein–RNA interfaces
Authors: Zhou Peng , Zou Jianwei , Tian Feifei , Shang Zhicai
Published: April 2009

A new method is described to measure the geometric similarity between protein–RNA interfaces quantitatively. The method is based on a procedure that dissects the interface geometry in terms of the spatial relationships between individual amino acid nucleotide pairs. Using this technique, we performed an all‐on‐all comparison of 586 protein–RNA interfaces deposited in the current Protein Data Bank, as the result, an interface–interface similarity score matrix was obtained. Based upon this matrix, hierarchical clustering was carried out which yielded a complete clustering tree for the 586 protein–RNA interfaces. By investigating the organizing behavior of the clustering tree and the SCOP classification of protein partners in complexes, a geometrically nonredundant, diverse data set (representative data set) consisting of 45 distinct protein–RNA interfaces was extracted for the purpose of studying protein–RNA interactions, RNA regulations, and drug design. We classified protein–RNA interfaces into three types. In type I, the families and interface structural classes of the protein partners, as well as the interface geometries are all similar. In type II, the interface geometries and the interface structural classes are similar, whereas the protein families are different. In type III, only the interface geometries are similar but the protein families and the interface structural classes are distinct. Furthermore, we also show two new RNA recognition themes derived from the representative data set. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
On list coloring Steiner triple systems
Authors: Haxell P. E. , Pei M.
Published: April 2009

We study the list chromatic number of Steiner triple systems. We show that for every integer s there exists n0=n0(s) such that every Steiner triple system on n points STS(n) with n≥n0 has list chromatic number greater than s. We also show that the list chromatic number of a STS(n) is always within a log n factor of its chromatic number. © 2009 Wiley Periodicals, Inc. J Combin Designs 17: 314–322, 2009
Role of connective tissue growth factor and its interaction with basic fibroblast growth factor and macrophage chemoattractant protein‐1 in skin fibrosis
Authors: Chujo Sonoko , Shirasaki Fumiaki , Kondo‐Miyazaki Miki , Ikawa Yuka , Takehara Kazuhiko
Published: April 2009

Activation of the immune system and abnormal growth of skin fibroblasts cause systemic sclerosis. Growth factors have various biological activities, including mediation of immune reactions. The growth factor family includes basic fibroblast growth factor (bFGF), transforming growth factor‐beta (TGF‐β), and connective tissue growth factor (CTGF). CTGF, an important downstream mediator of TGF‐β in fibrosis, has been suggested to play a specific role in fibrotic disorders. We have directed our attention to the role of CTGF in sustaining skin fibrosis. To better understand its effects in vivo, we established an animal model of skin fibrosis induced by exogenous application of growth factors. In this model, bFGF transiently induced subcutaneous fibrosis. Simultaneous injection of bFGF and CTGF increased skin fibrosis compared with a single injection of bFGF. Serial injections of bFGF for 3 days followed by CTGF for 4 days, or of CTGF followed by bFGF, did not cause skin fibrosis but simultaneous injections increased macrophage chemoattractant protein‐1 (MCP‐1) mRNA expression levels. To further define the mechanisms of skin fibrosis in vivo, bFGF and CTGF were injected simultaneously into MCP‐1 knockout mice, resulting in decreased collagen levels in granulation tissues on day 8. The number of inflammatory cells, such as mast cells, macrophages and lymphocytes, was significantly decreased in MCP‐1 knockout mice compared with wild‐type mice. These results suggest that bFGF induces collagen production by stimulating skin fibroblasts and CTGF cooperates with bFGF. Our results indicate that the induction of MCP‐1 is necessary for infiltration of inflammatory cells. J. Cell. Physiol. 220: 189–195, 2009. © 2009 Wiley‐Liss, Inc.
Glial cell‐derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF‐κB pathways
Authors: Su Chen‐Ming , Lu Dah‐Yuu , Hsu Chin‐Jung , Chen Hsien‐Te , Huang Chun‐Yin , Yang Wei‐Hung , Su Yi‐Chang , Yang Shu‐Ning , Fong Yi‐Chin , Tseng Wen‐Pei , Tang Chih‐Hsin
Published: April 2009

Invasion of tumor cells is the primary cause of therapeutic failure in the treatment of malignant chondrosarcomas. Glial cell‐derived neurotrophic factor (GDNF) plays a crucial role in migration and metastasis of human cancer cells. Integrins are the major adhesive molecules in mammalian cells. Here we found that GDNF directed the migration and increased cell surface expression of αv and β3 integrin in human chondrosarcoma cells. Pretreated of JJ012 cells with MAPK kinase (MEK) inhibitors PD98059 or U0126 inhibited the GDNF‐mediated migration and integrin expression. Stimulation of cells with GDNF increased the phosphorylation of MEK and extracellular signal‐regulating kinase (ERK). In addition, NF‐κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited GDNF‐mediated cells migration and integrin up‐regulation. Stimulation of cells with GDNF induced IκB kinase (IKKα/β) phosphorylation, IκB phosphorylation, p65 Ser536 phosphorylation, and κB‐luciferase activity. Furthermore, the GDNF‐mediated increasing of κB‐luciferase activity was inhibited by PD98059, U0126, PDTC and TPCK or MEK, ERK, IKKα, and IKKβ mutants. Taken together, these results suggest that the GDNF acts through MEK/ERK, which in turn activates IKKα/β and NF‐κB, resulting in the activations of αvβ3 integrin and contributing the migration of human chondrosarcoma cells. J. Cell. Physiol. 220: 499–507, 2009. © 2009 Wiley‐Liss, Inc.
Intranuclear fluorescence resonance energy transfer analysis of plasmid DNA decondensation from nonviral gene carriers
Authors: Matsumoto Yu , Itaka Keiji , Yamasoba Tatsuya , Kataoka Kazunori
Published: April 2009

Background

There has been considerable interest in researching the regulatory mechanisms that control transgene expression. In particular, there is impetus to investigate the intranuclear mechanisms for gene expression in order to improve the transfection efficiency of nonviral gene carriers.

Methods

To clarify the direct relationship between DNA decondensation and gene expression, plasmid DNA encoding Keima‐Red fluorescent protein was doubly‐labeled by a pair of donor–acceptor fluorescent dyes (fluorescein and Cy3), and transfected to HuH‐7 cells using nonviral gene carriers: polyethylenimine (polyplex) and LipofectAMINE 2000 (lipoplex). Fluorescence resonance energy transfer analysis between the two dyes represents the condensation state of the pDNA. The intranuclear trafficking and condensation state of the pDNA were explored in transgene expressing and non‐expressing cells under confocal laser scanning spectromicroscopy.

Results

The majority of transgene positively expressing cells transfected with polyplex and lipoplex had decondensed pixels in the nucleus. The majority of non‐expressing cells transfected with polyplex had only condensed pixels in the nucleus. The majority of non‐expressing cells transfected with lipoplex had no pixels in the nucleus.

Conclusions

Both polyplex and lipoplex marked a strong correlation between pDNA decondensation and transgene expression, yet the major limiting factor for transgene expression was different. In polyplex, the pDNA decondensation after nuclear entry was the major determining factor for transgene expression, whereas the nuclear entry itself was the chief determining step for transgene expression by lipoplex. This imaging technique allowed in situ observation of pDNA in the nucleus, providing important information about DNA behavior for gene expression. Copyright © 2009 John Wiley & Sons, Ltd.
Totally symmetric colored graphs
Authors: Grech Mariusz , Kisielewicz Andrzej
Published: April 2009

In this paper we describe almost all edge‐colored complete graphs that are fully symmetric with respect to colors and transitive on every set of edges of the same color. This generalizes the recent description of self‐complementary symmetric graphs by Peisert and gives examples of permutation groups that require more than 5 colors to be represented as the automorphism group of a k ‐colored graph. This also contributes to the recent study of homogeneous factorizations of complete graphs. The result relies on the classification of finite simple groups. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 329–345, 2009
d‐Regular graphs of acyclic chromatic index at least d+2
Authors: Basavaraju Manu , Chandran L. Sunil , Kummini Manoj
Published: April 2009

An acyclic edge coloring of a graph is a proper edge coloring such that there are no bichromatic cycles. The acyclic chromatic index of a graph is the minimum number k such that there is an acyclic edge coloring using k colors and is denoted by a′(G). It was conjectured by Alon, Sudakov and Zaks (and earlier by Fiamcik) that a′(G)⩽Δ+2, where Δ=Δ(G) denotes the maximum degree of the graph. Alon et al. also raised the question whether the complete graphs of even order are the only regular graphs which require Δ+2 colors to be acyclically edge colored. In this article, using a simple counting argument we observe not only that this is not true, but in fact all d‐regular graphs with 2n vertices and d>n, requires at least d+ 2 colors. We also show that a′(Kn, n)⩾n+ 2, when n is odd using a more non‐trivial argument. (Here Kn, n denotes the complete bipartite graph with n vertices on each side.) This lower bound for Kn, n can be shown to be tight for some families of complete bipartite graphs and for small values of n. We also infer that for every d, n such that d⩾5, n⩾2d+ 3 and dn even, there exist d‐regular graphs which require at least d+2‐colors to be acyclically edge colored. © 2009 Wiley Periodicals, Inc. J Graph Theory 63: 226–230, 2010
Selective reduction in microglia density and function in the white matter of colony‐stimulating factor‐1–deficient mice
Authors: Kondo Yoichi , Duncan Ian D.
Published: April 2009

It is still debated whether microglia play a beneficial or harmful role in myelin disorders such as multiple sclerosis and leukodystrophies as well as in other pathological conditions of the central nervous system. The osteopetrotic (op/op) mouse has reduced numbers of cells of monocyte lineage as a result of an inactivating mutation in the colony stimulating factor‐1 gene. To determine whether this mutant mouse might be used to study the role of microglia in myelin disorders, we quantified the number of microglia in the central nervous system of op/op mice and explored their ability to respond to brain injury created by a stab wound. Microglial density in the 2‐month‐old op/op mice was significantly decreased in the white matter tracts compared with the ‐ge matched wild‐type controls (by 63.6% in the corpus callosum and 86.4% in the spinal dorsal column), whereas the decrease was less in the gray matter, cerebral cortex (24.0%). A similar decrease was seen at 7 months of age. Morphometric studies of spinal cord myelination showed that development of myelin was not affected in op/op mice. In response to a stab wound, the increase in the number of microglia/macrophages in op/op mice was significantly less pronounced than that in wild‐type control. These findings demonstrate that this mutant is a valuable model in which to study roles of microglia/macrophages in the pathophysiology of myelin disorders. © 2009 Wiley‐Liss, Inc.
Adaptations in 5‐HT receptor expression and function: Implications for treatment of cognitive impairment in aging
Authors: Mitchell Ellen S. , McDevitt Ross A. , Neumaier John F.
Published: April 2009

Malfunction of the serotonin system may contribute to memory deficits during aging. We evaluated the 5‐HT6antagonist RO4368554 in two models of learning and memory in aged rats. Male rats (18 months) were assigned to two groups of equal cognitive performance. After 2 weeks of 5‐HT6antagonist RO4368554 (5 mg/kg, i.p.) treatment, rats showed significant improvement in object recognition and social discrimination compared with rats given chronic vehicle. Brains from these animals were examined for changes in plasticity‐associated proteins Ki‐67 and PCNA. No differences were seen between groups in any of these markers. We also measured mRNA expression of 5‐HT6, along with 5‐HT1A, 5‐HT1B, and tryptophan hydroxylase‐2 mRNAs in 4‐month‐old and 24‐month‐old F344 rats. Decreases in 5‐HT1Bexpression were observed in several forebrain regions in the old rats. These results demonstrate that 5‐HT6and 5‐HT1Breceptors are potential targets for treatment of age‐related memory disorders. © 2009 Wiley‐Liss, Inc.
Expression of SLURP‐1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells
Authors: Horiguchi Kazuhide , Horiguchi Satomi , Yamashita Naomi , Irie Kaoru , Masuda Junya , Takano‐Ohmuro Hiromi , Himi Toshiyuki , Miyazawa Mai , Moriwaki Yasuhiro , Okuda Takashi , Misawa Hidemi , Ozaki Hiroshi , Kawashima Koichiro
Published: April 2009

Mammalian secreted lymphocyte antigen‐6/urokinase‐type plasminogen activator receptor‐related peptide‐1 (SLURP‐1) is a positive allosteric ligand for α7 nicotinic acetylcholine (ACh) receptors (α7 nAChRs) that potentiates responses to ACh and elicits proapoptotic activity in human keratinocytes. Mutations in the gene encoding SLURP‐1 have been detected in patients with Mal de Meleda, a rare autosomal recessive skin disorder characterized by transgressive palmoplantar keratoderma. On the basis of these findings, SLURP‐1 is postulated to be involved in regulating tumor necrosis factor‐α (TNF‐α) release from keratinocytes and macrophages via α7 nAChR‐mediated pathways. In the present study, we assessed SLURP‐1 expression in lung tissue from C57BL/6J mice to investigate the functions of SLURP‐1 in pulmonary physiology and pathology. Immunohistochemical and in situ hybridization analyses revealed expression of SLURP‐1 protein and mRNA, respectively, exclusively in ciliated bronchial epithelial cells. This was supported by Western blotting showing the presence of the 9.5‐kDa SLURP‐1 protein in whole‐lung tissue and trachea. In addition, high‐affinity choline transporter (CHT1) was detected in apical regions of bronchial epithelial cells and in neurons located in the lamina propria of the bronchus, suggesting that bronchial epithelial cells are able to synthesize both SLURP‐1 and ACh. We also observed direct contact between F4/80‐positive macrophages and bronchial epithelial cells and the presence of invading macrophages in close proximity to CHT1‐positive nerve elements. Collectively, these results suggest that SLURP‐1 contributes to the maintenance of bronchial epithelial cell homeostasis and to the regulation of TNF‐α release from macrophages in bronchial tissue. © 2009 Wiley‐Liss, Inc.
Isatin binding proteins in rat brain: In situ imaging, quantitative characterization of specific [3H]isatin binding, and proteomic profiling
Authors: Crumeyrolle‐Arias Michele , Buneeva Olga , Zgoda Victor , Kopylov Arthur , Cardona Ana , Tournaire Marie‐Claude , Pozdnev Vladimir , Glover Vivette , Medvedev Alexei
Published: April 2009

Isatin (indole‐2,3‐dione) is an endogenous indole that has a distinct and discontinuous distribution in the brain and in other mammalian tissues and body fluids. Its output is increased under conditions of stress and anxiety. Its biological targets remain poorly characterized, although [3H]isatin binding sites have been demonstrated in various brain structures. In this study, by using a real‐time beta‐imager, [3H]isatin radioligand binding analysis, and proteomic identification of proteins specifically bound to the affinity sorbent 5‐aminocaproyl‐isatin‐Sepharose, we have investigated the distribution of [3H]isatin specific binding sites in the rat brain, characterized their Kd and Bmax, and identified some individual brain isatin binding proteins. The binding of [3H]isatin to rat brain sections was saturable and characterized by Kd values (of 0.2–0.3 μM) consistent with physiological concentrations. The highest Bmax was found in the hypothalamus, consistent with a role in stress. In most brain regions, the homologous inhibition of [3H]isatin binding by increasing concentrations of cold isatin demonstrated complex behavior suggesting involvement of various binding proteins characterized by different affinity to isatin. Affinity chromatography of Triton X‐100 lysates of whole‐brain homogenates on 5‐aminocaproyl‐isatin‐Sepharose followed by subsequent proteomic analysis resulted in identification of 25 individual proteins, including glyceraldehyde‐3‐phosphate dehydrogenase, one of few previously reported isatin binding proteins, and a group of cytoskeleton‐related proteins. These binding sites may be related to the known antiproliferative and proapoptotic activities of isatin. © 2009 Wiley‐Liss, Inc.
Localization of the full‐thickness cartilage lesions in medial and lateral unicompartmental knee osteoarthritis
Authors: Gulati Aashish , Chau Ryan , Beard David J. , Price Andrew J. , Gill Harinderjit S. , Murray David W.
Published: April 2009

This study's aim was to determine the patterns of osteoarthritis (OA) in both unicompartmental medial and lateral OA of the knee. Forty patients with medial and 20 with lateral unicompartmental knee osteoarthritis were studied to determine the location of full‐thickness cartilage lesions. Intraoperatively, the distance between margins of the lesion and reference lines were measured. The femoral measurements were transposed onto lateral radiographs to determine the relationship between the lesion site and knee flexion angles. Both tibial and femoral lesions were significantly (p < 0.01) more posterior in lateral OA than medial OA. In medial OA, the lesion center was, on average, at 11° (SD 3°) of flexion, whereas in lateral OA, it was at 40° (SD 3°). The smallest medial femoral lesions were near full extension and, as they enlarged, they extended posteriorly. The smallest lateral femoral lesions extended from 20° to 60° flexion. As these lesions enlarged, they extended both anteriorly and posteriorly. There was a well‐defined relationship between the site of the lesions and their size, suggesting that they develop and progress in a predictable manner. The relationship was different for medial and lateral OA, suggesting that different mechanical factors are important in initiating the different types of OA. The lesions in medial OA occur in extension, perhaps initiated by events occurring at heel strike. The lesions in lateral OA begin at flexion angles above those occurring during the single leg stance phase of the gait cycle, so activities other than gait are likely to induce lateral OA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1339–1346, 2009