bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methotrexate chemotherapy reduces osteogenesis but increases adipogenic potential in the bone marrow
Authors: Georgiou Kristen R. , Scherer Michaela A. , Fan Chia‐Ming , Cool Johanna C. , King Tristan J. , Foster Bruce K. , Xian Cory J. 
Published: April 2011

AbstractIntensive use of cancer chemotherapy is increasingly linked with long‐term skeletal side effects such as osteopenia, osteoporosis and fractures. However, cellular mechanisms by which chemotherapy affects bone integrity remain unclear. Methotrexate (MTX), used commonly as an anti‐metabolite, is known to cause bone defects. To study the pathophysiology of MTX‐induced bone loss, we examined effects on bone and marrow fat volume, population size and differentiation potential of bone marrow stromal cells (BMSC) in adult rats following chemotherapy for a short‐term (five once‐daily doses at 0.75 mg/kg) or a 6‐week term (5 doses at 0.65 mg/kg + 9 days rest + 1.3 mg/kg twice weekly for 4 weeks). Histological analyses revealed that both acute and chronic MTX treatments caused a significant decrease in metaphyseal trabecular bone volume and an increase in marrow adipose mass. In the acute model, proliferation of BMSCs significantly decreased on days 3–9, and consistently the stromal progenitor cell population as assessed by CFU‐F formation was significantly reduced on day 9. Ex vivo differentiation assays showed that while the osteogenic potential of isolated BMSCs was significantly reduced, their adipogenic capacity was markedly increased on day 9. Consistently, RT‐PCR gene expression analyses showed osteogenic transcription factors Runx2 and Osterix (Osx) to be decreased but adipogenic genes PPARγ and FABP4 up‐regulated on days 6 and 9 in the stromal population. These findings indicate that MTX chemotherapy reduces the bone marrow stromal progenitor cell population and induces a switch in differentiation potential towards adipogenesis at the expense of osteogenesis, resulting in osteopenia and marrow adiposity. J. Cell. Physiol. 227: 909–918, 2012. © 2011 Wiley Periodicals, Inc.
Proteomics applied to exercise physiology: A cutting‐edge technology
Authors: Petriz Bernardo A. , Gomes Clarissa P. , Rocha Luiz A. O. , Rezende Taia M. B. , Franco Octávio L. 
Published: April 2011

AbstractExercise research has always drawn the attention of the scientific community because it can be widely applied to sport training, health improvement, and disease prevention. For many years numerous tools have been used to investigate the several physiological adaptations induced by exercise stimuli. Nowadays a closer look at the molecular mechanisms underlying metabolic pathways and muscular and cardiovascular adaptation to exercise are among the new trends in exercise physiology research. Considering this, to further understand these adaptations as well as pathology attenuation by exercise, several studies have been conducted using molecular investigations, and this trend looks set to continue. Through enormous biotechnological advances, proteomic tools have facilitated protein analysis within complex biological samples such as plasma and tissue, commonly used in exercise research. Until now, classic proteomic tools such as one‐ and two‐dimensional polyacrylamide gel electrophoresis have been used as standard approaches to investigate proteome modulation by exercise. Furthermore, other recently developed in gel tools such as differential gel electrophoresis (DIGE) and gel‐free techniques such as the protein labeling methods (ICAT, SILAC, and iTRAQ) have empowered proteomic quantitative analysis, which may successfully benefit exercise proteomic research. However, despite the three decades of 2‐DE development, neither classic nor novel proteomic tools have been convincingly explored by exercise researchers. To this end, this review gives an overview of the directions in which exercise‐proteome research is moving and examines the main tools that can be used as a novel strategy in exercise physiology investigation. J. Cell. Physiol. 227: 885–898, 2012. © 2011 Wiley Periodicals, Inc.
Role of neurotrophins on dermal fibroblast survival and differentiation
Authors: Palazzo Elisabetta , Marconi Alessandra , Truzzi Francesca , Dallaglio Katiuscia , Petrachi Tiziana , Humbert Philippe , Schnebert Sylvianne , Perrier Eric , Dumas Marc , Pincelli Carlo 
Published: April 2011

AbstractNeurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low‐affinity receptor p75NTR and the high‐affinity receptors TrkA, TrkB, and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of α‐SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc, or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue re‐modeling and wound healing. J. Cell. Physiol. 227: 1017–1025, 2012. © 2011 Wiley Periodicals, Inc.
Quantification of α‐ and β‐amyrin in rat plasma by gas chromatography–mass spectrometry: application to preclinical pharmacokinetic study
Authors: Ching Jianhong , Lin Hai‐Shu , Tan Chay‐Hoon , Koh Hwee‐Ling 
Published: April 2011

Abstractα‐ and β‐Amyrins are naturally occurring triterpenes with a wide range of biological activities. In this study, a reliable GC‐MS method was developed and validated for the quantification of α‐ and β‐amyrins in rat plasma. The calibration curves were linear (R2 > 0.996) with a limit of quantification of 1.0 ng ml−1 for both α‐ and β‐amyrins. The precision and repeatability of this method was good as the relative standard deviation were 12% or less. The absolute recovery ranged from 71% to 89%, while the analytical recovery ranged from 95% to 99%. The pharmacokinetic profiles of α‐ and β‐amyrins in rats were subsequently investigated in Sprague‐Dawley rats. β‐Amyrin was administered intravenously and also orally in two forms, namely, as a suspension of the pure compound and the crude plant extract. α‐Amyrin was administered orally as a suspension of the crude plant extract. β‐Amyrin had a very long terminal elimination half‐life (t1/2λz = 610 ± 179 min) and extremely slow clearance (Cl = 2.04 ± 0.24 ml min−1 kg−1). The absolute oral bioavailability of β‐amyrin in the crude plant extract was about fourfold higher than that in the suspension of pure form (3.83% vs 0.86%). When given in crude plant extract, both α‐ and β‐amyrins had a similar dose normalized Cmax. This reliable GC‐MS method will enable further pharmacokinetic investigations of α‐ and β‐amyrins. Copyright © 2011 John Wiley & Sons, Ltd.
Gas‐phase chemistry of ionized and protonated GeF4: a joint experimental and theoretical study
Authors: Antoniotti Paola , Bottizzo Elena , Operti Lorenza , Rabezzana Roberto , Borocci Stefano , Grandinetti Felice 
Published: April 2011

AbstractThe gas‐phase ion chemistry of GeF4 and of its mixtures with water, ammonia and hydrocarbons was investigated by ion trap mass spectrometry (ITMS) and ab initio calculations. Under ITMS conditions, the only fragment detected from ionized GeF4 is GeF3+. This cation is a strong Lewis acid, able to react with H2O, NH3 and the unsaturated C2H2, C2H4 and C6H6 by addition‐HF elimination reactions to form F2Ge(XH)+, FGe(XH)2+, Ge(XH)3+ (X = OH or NH2), F2GeC2H+, F2GeC2H3+ and F2GeC6H5+. The structure, stability and thermochemistry of these products and the mechanistic aspects of the exemplary reactions of GeF3+ with H2O, NH3 and C6H6 were investigated by MP2 and coupled cluster calculations. The experimental proton affinity (PA) and gas basicity (GB) of GeF4 were estimated as 121.5 ± 6.0 and 117.1 ± 6.0 kcal mol−1, respectively, and GeF4H+ was theoretically characterized as an ion‐dipole complex between GeF3+ and HF. Consistently, it reacts with simple inorganic and organic molecules to form GeF3+‐L complexes (L = H2O, NH3, C2H2, C2H4, C6H6, CO2, SO2 and GeF4). The theoretical investigation of the stability of these ions with respect to GeF3+ and L disclosed nearly linear correlations between their dissociation enthalpies and free energies and the PA and GB of L. Comparing the behavior of GeF3+ with the previously investigated CF3+ and SiF3+ revealed a periodically reversed order of reactivity CF3+ < GeF3+ < SiF3+. This parallels the order of the Lewis acidities of the three cations. Copyright © 2011 John Wiley & Sons, Ltd.
Unimolecular rearrangements of ketene‐O,O‐acetals and fragmentations occurring in the gas phase
Authors: Morales‐Ríos Martha S. , López‐Camacho Perla Y. , Jacobo‐Cabral Carlos O. , Pérez‐Rojas Nadia A. , Trujillo‐Serrato Joel J. , Burgueño‐Tapia Eleuterio , Suárez‐Castillo Oscar R. , Joseph‐Nathan Pedro 
Published: April 2011

AbstractGas phase skeletal rearrangements of regioisomeric 3‐cyano‐2‐methoxy‐3a‐alkylfuro[2,3‐b]‐ and [3,2‐b]indoles were evidenced by product ions [M − 32]+•, consistent with loss of methanol, on electron ionization in their mass spectra. The rearranged products occurring in gas phase were demonstrated to have elemental composition and fragmentation properties identical to those of authentic samples of 2‐indolyl cyanomalonates. Isotopic labeling experiments support the formation mechanism of the [M − 32]+• ion. Additional thermal gas‐phase reaction products were characterized by comparison with an authentic sample. Copyright © 2011 John Wiley & Sons, Ltd.
Simultaneous determination of serine enantiomers in plasma using Mosher's reagent and stable isotope dilution gas chromatography‐mass spectrometry
Authors: Hasegawa Hiroshi , Shinohara Yoshihiko , Masuda Nami , Hashimoto Takao , Ichida Kimiyoshi 
Published: April 2011

AbstractD‐Serine is a co‐agonist of the N‐methyl‐D‐aspartate receptor in glutamate neurotransmission and has been proposed as a potential therapeutic agent for schizophrenia. However, D‐serine also acts as a nephrotoxic substance in rats at high doses. To investigate the pharmacokinetics and toxicokinetics of D‐serine, a method for the stereoselective determination of serine enantiomers in rat plasma was developed using GC‐MS with selected ion monitoring (GC‐MS‐SIM). DL‐[2H3]Serine was used as an internal standard to account for losses associated with the extraction, derivatization and chromatography. Serine enantiomers were purified by cation‐exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N,O‐diacylation with optically active (+)‐α‐methoxy‐α‐trifluoromethylphenylacetyl chloride to form epimeric amide. Quantitation was performed by SIM of the molecular‐related ions of the epimers in the chemical ionization mode. The intra‐ and inter‐day reproducibility of the assay was less than 5% for D‐serine and 3% for L‐serine. The method was successively applied to study the pharmacokinetics of D‐serine in rats. Copyright © 2011 John Wiley & Sons, Ltd.
Lymphoproliferative disorders in individuals with chronic hepatitis b and C in the Turkish population
Authors: Idilman Ramazan , Bozkus Yusuf , Seval Guldane , Mizrak Dilsa , Cinar Kubilay , Ustun Yusuf , Bektas Mehmet , Arat Mutlu , Akbulut Hakan , Doganay Beyza , Ozden Ali 
Published: April 2011

AbstractThe aims of this cohort study were to evaluate the association of malignant lymphoproliferative disorders in patients with chronic viral hepatitis and to compare the results with those in individuals with non‐alcoholic fatty liver disease. A total of 3,873 patients with chronic liver disease who were seen consecutively in the Liver Disease Outpatient Clinic between January 2001 and July 2007 were assessed retrospectively. The frequency of malignant lymphoproliferative disorders including non‐Hodgkin's lymphoma, Hodgkin's lymphoma, and chronic lymphocytic leukemia in these patients was investigated. Of the total, 1,999 patients had chronic hepatitis B infection (male/female: 1,226/773, mean age: 45.1 ± 13.2 years), 978 had chronic hepatitis C infection (male/female: 437/541, mean age: 53.8 ± 13.7 years), and the remaining 896 had non‐alcoholic fatty liver disease (male/female: 450/446, mean age: 50.8 ± 11.2 years). A malignant lymphoproliferative disorder was identified in 13 patients (male/female: 9/4, mean age: 52.8 ± 16.8 years) with chronic viral hepatitis, while no case of malignant lymphoproliferative disorder was identified in individuals with non‐alcoholic fatty liver disease (P = 0.048). Among the patients with malignant lymphoproliferative disorders, seven had chronic hepatitis B infection and six had chronic hepatitis C infection; 11 had non‐Hodgkin's lymphoma and two had chronic lymphocytic leukemia. All non‐Hodgkin's lymphoma cases were B‐cell lymphoma. Based on the data obtained in this investigation, the association with malignant lymphoproliferative disorders in chronic viral hepatitis seems to be high as compared to that occurring in individuals with non‐alcoholic fatty liver disease. J. Med. Virol. 83:974–980, 2011. © 2011 Wiley‐Liss, Inc.
Full genome characterization of hepatitis B virus strains from blood donors in Iran
Authors: Garmiri Penelope , Rezvan Houri , Abolghasemi Hassan , Allain Jean‐Pierre 
Published: April 2011

AbstractIran is a low to medium endemic country for hepatitis B virus (HBV), depending on the region, where genotype D is dominant. Samples from 170 asymptomatic HBsAg‐positive blood donors were quantified and the median viral load was 6.7 × 102 IU/ml with 10.6% samples unquantifiable. Fifty complete genome sequences of these strains were characterized. Phylogenetic analysis identified 98% strains as subgenotype D1 and 2% as D2. Deduced serotypes were ayw2 (94%), ayw1 (4%), and adw (2%). The nucleotide diversity of the complete genome subgenotype D1 Iranian strains was limited (2.8%) and comparison with D1 strains from Egypt and Tunisia revealed little variation between strains from these three countries (range 1.9–2.8%). The molecular analysis of the individual genes revealed that the G1896A mutation was present in 86.2% of the strains and in 26 strains (29.9%) this mutation was accompanied by the G1899A mutation. The double mutations A1762T/G1764A and G1764T/C1766G were found in 20.7% and 24.1% of the strains, respectively. The pre‐C initiation codon was mutated in five strains (5.8%). One strain had a 2‐amino acid (aa) insertion at position s111 and another sP120Q substitution suggesting a vaccine escape mutant. J. Med. Virol. 83:948–952, 2011. © 2011 Wiley‐Liss, Inc.
Clinical course and predictive factors of virological response in long‐term lamivudine plus adefovir dipivoxil combination therapy for lamivudine‐resistant chronic hepatitis B patients
Authors: Aizawa Mashu , Tsubota Akihito , Fujise Kiyotaka , Tatsuzawa Keiko , Kono Midori , Hoshina Sadayori , Tajiri Hisao 
Published: April 2011

AbstractThe aims of this study were to assess the long‐term efficacy of lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy in patients with chronic hepatitis B resistant to LAM, to identify predictive factors of complete viral response (HBV‐DNA <2.6 log copies/ml at 12 months of combination therapy), and to analyze amino acid substitutions associated with treatment resistance in the hepatitis B virus (HBV) genome. Seventy‐two patients who received ADV in addition to LAM for breakthrough hepatitis were enrolled. Undetectable HBV‐DNA was observed in 61%, 74%, 81%, 84%, and 85% at 12, 24, 36, 48, and 60 months of combination therapy, respectively. On multivariate analysis, undetectable HBV‐DNA during the preceding LAM monotherapy (P < 0.0001), alanine aminotransferase value ≥ the upper limit of normal × 6 (P = 0.006) and HBV‐DNA level < 6.0 log copies/ml at the initiation of combination therapy (P = 0.007) were independent significant predictors of complete viral response. The cumulative rate of undetectable HBV‐DNA was significantly higher in patients with response to the preceding LAM monotherapy than in those with poor response to it. Breakthrough hepatitis occurred in three patients without complete viral response and with poor response to the preceding LAM monotherapy, and rtA181A/V substitution was detected in one of the three patients. In conclusion, undetectable HBV‐DNA during the LAM monotherapy was the strongest independent predictor of complete viral response to the following combination therapy. The efficacy of LAM plus ADV combination therapy may be determined by viral response to the preceding LAM monotherapy. J. Med. Virol. 83:953–961, 2011. © 2011 Wiley‐Liss, Inc.
Prediction of response to peginterferon‐alfa‐2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b
Authors: Hashimoto Yoshimasa , Ochi Hidenori , Abe Hiromi , Hayashida Yasufumi , Tsuge Masataka , Mitsui Fukiko , Hiraga Nobuhiko , Imamura Michio , Takahashi Shoichi , Nelson Hayes C. , Ohishi Waka , Kubo Michaki , Tsunoda Tatsuhiko , Kamatani Naoyuki , Nakamura Yusuke , Chayama Kazuaki 
Published: April 2011

AbstractVariation at the IL‐28B locus was recently reported to be a significant predictive factor of viral response to pegylated‐interferon plus ribavirin combination therapy against chronic hepatitis C. Predictive factors for the effect of therapy, including IL‐28B polymorphism rs8099917 and viral and clinical factors were investigated. A total of 288 patients were enrolled who were chronically infected with hepatitis C virus (HCV) genotype 1b and treated with combination therapy. Among them, 87 patients completed 48 weeks of therapy without dose reduction or discontinuation. In multivariate regression analysis, the rs8099917 TT genotype was the only independent factor significantly associated with sustained viral response (P = 0.016, OR 61.5), whereas substitutions at amino acid 70 (aa 70) of the HCV core protein (P = 0.038, OR 5.9) and non‐TT genotypes (P = 0.002, OR 17.2) were associated with nonvirological response. Both factors were also associated with viral dynamics during the initial stage of the therapy. Correlation analysis revealed that rs8099917 genotype was correlated with γ‐glutamyl transpeptidase, hyaluronic acid, and HCV core aa 70. In conclusion, host (IL‐28B polymorphism) and viral (aa 70) factors independently affect response to combination therapy. J. Med. Virol. 83:981–988, 2011. © 2011 Wiley‐Liss, Inc.
Common genetic polymorphism of ITPA gene affects ribavirin‐induced anemia and effect of peg‐interferon plus ribavirin therapy
Authors: Azakami Takahiro , Hayes C. Nelson , Sezaki Hitomi , Kobayashi Mariko , Akuta Norio , Suzuki Fumitaka , Kumada Hiromitsu , Abe Hiromi , Miki Daiki , Tsuge Masataka , Imamura Michio , Kawakami Yoshiiku , Takahashi Shoichi , Ochi Hidenori , Nakamura Yusuke , Kamatani Naoyuki , Chayama Kazuaki 
Published: April 2011

AbstractAn association between a single nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and reduction of hemoglobin during peg‐interferon plus ribavirin combination therapy for patients with chronic hepatitis C virus (HCV) infection has been reported. However, the effect of the SNP on outcome of therapy has not been fully elucidated. Factors associated with anemia during combination therapy, including rs1127354 genotype, were analyzed in 1,002 treated patients. The effect of the SNP on outcome of therapy was analyzed in a subset of 830 patients with genotype 1. A rapid initial decrease in hemoglobin levels was observed in patients with rs1127354 genotype CC compared with a slow decrease in non‐CC patients. Cumulative reduction of ribavirin was significantly more frequent in genotype CC patients than non‐CC patients (odds ratio 1.928, P = 8.6 × 10−8). The frequency of patients who received at least the recommended 80% of scheduled ribavirin was significantly lower among genotype CC patients, especially among those who had pretreatment hemoglobin levels between 13.5 and 15 g/dl (P < 0.03), and the sustained viral response rate was significantly lower in this group of patients. Independent predictive factors for sustained virological response included a SNP in the IL28B locus (rs809991), age, fibrosis, ITPA SNP rs1127354 as well as pretreatment hemoglobin levels. Our data suggests that measures to prevent anemia should be considered for patients who have pretreatment hemoglobin levels less than 13.5 g/dl or who have rs1127354 genotype CC and pretreatment hemoglobin levels between 13.5 and 15 g/dl. J. Med. Virol. 83:1048–1057, 2011. © 2011 Wiley‐Liss, Inc.
The early phase of an HIV epidemic in a population exposed previously to HCV in the Philippines
Authors: Telan Elizabeth Freda O. , Samonte Genesis May J. , Abellanosa‐Tac‐An Ilya P. , Alesna Evelyn T. , Leaño Prisca Susan A. , Emphasis Yvonne Ethyl E. , Tsuneki Akeno , Matsumoto Keita , Kageyama Seiji 
Published: April 2011

AbstractHuman immunodeficiency virus (HIV) sentinel surveillance program for injecting drug users has been conducted in Metro Cebu, the Philippines. A low prevalence (0–0.52%) of anti‐HIV‐positivity had been detected in this population from 2002 to 2007. However, a 10‐fold increase in HIV prevalence was detected in the 2009 national HIV sentinel surveillance program. It prompted an additional outreach program to be conducted in Metro Cebu in January 2010, which recorded the highest HIV prevalence rate ever documented in the Philippines (75%, 44/59). HIV genes from fourteen 2009 to 2010 Metro Cebu strains were clustered closely in the phylogenetic tree, but no other strain collected outside Metro Cebu and none stored in the International Nucleotide Sequence Database was allocated to the same phylogenetic cluster. All these HIV infections have emerged in the anti‐hepatitis C virus (HCV)‐positive population (100%, 62/62) in Metro Cebu from 2009 to 2010. The five HCV strains from the individuals harboring the closely related HIV strains were categorized into different subtypes. These results strongly suggest that HIV infections occurred recently and spread rapidly among injecting drug users, while HCV had been circulating previously among them. Considering the fact that injecting drug use was the first mode of HIV transmission in Asia, extensive monitoring of injecting drug users and associated bridging populations is necessary. Therefore, HCV‐guided characterization of the spread of HIV to populations that are vulnerable to blood‐borne infections could play an important role in alerting health authorities to the early phase of an HIV epidemic. J. Med. Virol. 83:941–947, 2011. © 2011 Wiley‐Liss, Inc.
Evaluation of human polyomavirus BK as a potential cause of villitis of unknown etiology and spontaneous abortion
Authors: Cajaiba Mariana M. , Parks W.T. , Fuhrer K. , Randhawa P.S. 
Published: April 2011

AbstractPolyomavirus BK (BKV) is a widely latent pathogen in man. Although viral reactivation during pregnancy has been demonstrated, and polyomaviruses have been linked to chromosomal abnormalities, a pathogenic role for BKV in fetoplacental disease has not been explored. We performed in situ hybridization studies with BKV probes on cases of villitis of unknown etiology (102), diffuse villitis (25), and spontaneous abortion (22). We found no evidence that BKV plays a role in the pathogenesis of these common fetoplacental disorders. J. Med. Virol. 83:1031–1033, 2011. © 2011 Wiley‐Liss, Inc.