bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐circulation and cell distribution kinetics in parabiotic mice
Authors: Gibney Barry C. , Chamoto Kenji , Lee Grace S. , Simpson Dinee C. , Miele Lino F. , Tsuda Akira , Konerding Moritz A. , Wagers Amy , Mentzer Steven J.
Published: April 2011

Blood‐borne nucleated cells participate not only in inflammation, but in tissue repair and regeneration. Because progenitor and stem cell populations have a low concentration in the blood, the circulation kinetics and tissue distribution of these cells is largely unknown. An important approach to tracking cell lineage is the use of fluorescent tracers and parabiotic models of cross‐circulation. Here, we investigated the cross‐circulation and cell distribution kinetics of C57/B6 GFP+/wild‐type parabionts. Flow cytometry analysis of the peripheral blood after parabiosis demonstrated no evidence for a “parabiotic barrier” based on cell size or surface characterstics; all peripheral blood cell subpopulations in this study reached equilibrium within 14 days. Whole blood fluorescence analysis indicated that the mean exchange flow rate was 16 µl/h or 0.66% of the circulating blood volume per hour. Studies of peripheral lymphoid organs indicated differential cell distribution kinetics. Some subpopulations, such as CD8+ and CD11c+, equilibrated in both lymph nodes and spleen indicating a residence time <28 days; in contrast, other lymphocyte subpopulations, such as B220+ and CD4+ cells, had not yet reached equilibrium at 28 days. We conclude that parabiosis can provide important insights into defining tissue distribution, residence times, and recirculating pools using fluorochrome markers of cell lineage. J. Cell. Physiol. 227: 821–828, 2012. © 2011 Wiley Periodicals, Inc.
Phosphorylation of histone H1 by P‐TEFb is a necessary step in skeletal muscle differentiation
Authors: O'Brien Siobhan K. , Knight Kendall L. , Rana Tariq M.
Published: April 2011

Positive transcription elongation factor b (P‐TEFb), the complex of Cyclin T1 and CDK9, activates the transcription of many viral and eukaryotic genes at the point of mRNA elongation. The activity of P‐TEFb has been implicated in the differentiation of a number of cell types, including skeletal muscle. In order to promote transcription, P‐TEFb hyperphosphorylates RNA Pol II, thereby increasing its processivity. Our previous work identified histone H1 as a P‐TEFb substrate during HIV‐1 and immediate‐early transcription. Here, we examine the role of P‐TEFb phosphorylation of histone H1 during differentiation, using the myoblast cell line C2C12 as a model for skeletal muscle differentiation. We found that H1 phosphorylation is elevated in differentiating C2C12, and this phosphorylation is sensitive to P‐TEFb inhibition. H1 phosphorylation was also necessary for the induction of three muscle marker genes that require P‐TEFb for expression. Additionally, ChIP experiments demonstrate that H1 dissociates from muscle differentiation marker genes in C2C12 cells under active P‐TEFb conditions. We determine that both P‐TEFb activity and H1 phosphorylation are necessary for the full differentiation of C2C12 myoblasts into myotubes. J. Cell. Physiol. 227: 383–389, 2012. © 2011 Wiley Periodicals, Inc.
Functional regulation of HIF‐1α under normoxia—is there more than post‐translational regulation?
Authors: Kuschel A. , Simon P. , Tug S.
Published: April 2011

The hypoxia‐inducible factor‐1 (HIF‐1) is an oxygen‐regulated transcriptional activator playing a pivotal role in mammalian physiology and disease pathogenesis, e.g., HIF‐1 is indispensable in a broad range of developmental stages in different tumors. Its post‐translational regulation via PHDs under the influence of hypoxia is widely investigated and accepted. Different non‐hypoxic stimuli such as lipopolysaccharides (LPS), thrombin, and angiotensin II (Ang II), have been proven to enhance HIF‐1 levels through activation of regulative mechanisms distinct from protein stabilization. Some of these stimuli specifically regulate HIF‐1α at the transcriptional, post‐transcriptional, or translational level, whereas others additionally influence post‐translational modifications. Thus, it is difficult for the investigators to discern the impact of the different mechanisms leading to functional HIF‐1 protein. Nevertheless, profound knowledge of additional regulatory networks appears to depict new therapeutic opportunities and thus is an interesting and important field for further investigations. J. Cell. Physiol. 227: 514–524, 2012. © 2011 Wiley Periodicals, Inc.
Nicotinamide inhibits the early stage of carcinogen‐induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growth
Authors: Park Soo Young , Lee Kyoung Bun , Lee Min‐Jae , Bae Suk‐Chul , Jang Ja‐June
Published: April 2011

Hepatocellular carcinoma (HCC) can cause severe complications, resulting in a high incidence of recurrence after treatment of the primary tumor. Recently, we have shown that nicotinamide effectively inhibits the growth and progression of bladder tumors by up‐regulating RUNX3 and p300 expression. Therefore, in this study, the efficacy and inhibitory mechanisms of nicotinamide against HCC were investigated in mice and HCC cell lines, respectively. To evaluate the inhibitory effects of nicotinamide on HCC development, mice were injected with diethylnitrosamine (DEN) and simultaneously treated with 1% nicotinamide. Also, the effect of nicotinamide on human HCC cell lines was assessed by measuring caspase activity, cell proliferation, and DNA content using immunoblot analysis and reverse‐transcriptase polymerase chain reaction. It was found that nicotinamide significantly inhibited the development of pre‐neoplastic lesions (foci and adenomas) during the early stages of HCC. Furthermore, nicotinamide inhibited cell proliferation and induced mitochondria‐mediated apoptosis in HCC cell lines. It also increased the expression of p21, and the expression and acetylation of p53. These results strongly suggest that nicotinamide inhibits the progression of early‐stage HCC and may contribute to the induction of apoptosis and the inhibition of proliferation of HCC cells. Taken together, the results of this study indicate that nicotinamide is a potential chemopreventive agent, i.e., it may prevent the progression of early HCC development and/or the recurrence of HCC after primary treatment. J. Cell. Physiol. 227: 899–908, 2012. © 2011 Wiley Periodicals, Inc.
Indomethacin enhances learning and memory potential by interacting with CaMKII
Authors: Kanno Takeshi , Yaguchi Takahiro , Nagata Tetsu , Shimizu Tadashi , Tanaka Akito , Nishizaki Tomoyuki
Published: April 2011

The present study examined the effect of indomethacin (IM), a cyclooxygenase inhibitor, on learning and memory functions. IM activated Ca2+/calmodulin‐dependent protein kinase II (CaMKII) in cultured rat hippocampal neurons. IM (100 µM) significantly increased the rate of spontaneous AMPA receptor‐mediated miniature excitatory postsynaptic currents elicited from CA1 pyramidal neurons of rat hippocampal slices, without affecting the amplitude, and enhanced extracellular high K+ (20 mM)‐induced glutamate release from rat hippocampal slices, indicating that IM stimulates presynaptic glutamate release. Those IM effects were clearly inhibited by the CaMKII inhibitor KN‐93. IM persistently facilitated synaptic transmission monitored from the CA1 region of rat hippocampal slices in a concentration (1–100 µM)‐dependent manner that was also abolished by KN‐93. In the water maze test, IM (1 mg/kg, i.p.) enhanced spatial learning and memory ability for normal rats, and ameliorated scopolamine‐induced spatial learning and memory impairment or age‐related spatial learning and memory deterioration for senescence‐accelerated mouse‐prone 8 mice. In the test to learn 15 numbers consisting of three patterns of five digit number for healthy human subjects, oral intake with IM (25 mg/kg) significantly raised the scores of correct number arrangements that subjects memorized 5 min and 3 days after the test. The results of the present study indicate that IM could enhance learning and memory potential by facilitating hippocampal synaptic transmission as a result from stimulating presynaptic glutamate release under the control of CaMKII. J. Cell. Physiol. 227: 919–926, 2012. © 2011 Wiley Periodicals, Inc.
Identification of a functional estrogen‐responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines
Authors: Abbondanza Ciro , De Rosa Caterina , D'Arcangelo Andrea , Pacifico Marianna , Spizuoco Clorinda , Piluso Giulio , Di Zazzo Erika , Gazzerro Patrizia , Medici Nicola , Moncharmont Bruno , Alfredo Puca Giovanni
Published: April 2011

The retinoblastoma protein‐interacting zinc‐finger (RIZ) gene, also known as PRDM2, encodes two protein products, RIZ1 and RIZ2, differing for the presence of a 202 aa domain, called PR domain, at the N‐terminus of the RIZ1 molecule. While the histone H3 K9 methyltransferase activity of RIZ1 is associated with the negative control of cell proliferation, no information is currently available on either expression regulation of the RIZ2 form or on its biological activity. RIZ proteins act as ER co‐activators and promote optimal estrogen response in female reproductive tissues. In estrogen‐responsive cells, 17‐β estradiol modulates RIZ gene expression producing a shift in the balanced expression of the two forms. Here, we demonstrate that an estrogen‐responsive element (ERE) within the RIZ promoter 2 is regulated in a ligand‐specific manner by ERα, through both the AF1 and AF2 domains. The pattern of ERα binding, histone H4 acetylation, and histone H3 cyclical methylation of lysine 9 was comparable to other estrogen‐regulated promoters. Association of topoisomerase IIβ with the RIZ promoter 2 confirmed the transcriptional activation induced by estrogen. We hypothesize that RIZ2, acting as a negative regulator of RIZ1 function, mediates the proliferative effect of estrogen through regulation of survival and differentiation gene expression. J. Cell. Physiol. 227: 964–975, 2012. © 2011 Wiley Periodicals, Inc.
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

Intensive 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

Exercise 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

Neurotrophins (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

α‐ 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

The 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

Gas 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

D‐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

The 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

Iran 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

The 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

Variation 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

An 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

Human 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

Polyomavirus 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.
Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy
Authors: Akuta Norio , Suzuki Fumitaka , Hirakawa Miharu , Kawamura Yusuke , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: April 2011

Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV‐1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV‐related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow‐up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow‐up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV‐1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV‐1b/Arg70 (arginine at aa 70) (P = 0.007; log‐rank test) and HCV‐2a/2b (P < 0.001; log‐rank test). The rates in patients infected with HCV‐1b/Arg70 were not significantly higher than in those infected with HCV‐2a/2b (P = 0.617; log‐rank test). Multivariate analysis identified HCV‐1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV‐1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy. J. Med. Virol. 83:1016–1022, 2011. © 2011 Wiley‐Liss, Inc.
Intra‐individual processes linking work and employee well‐being: Introduction into the special issue
Authors: Sonnentag Sabine , Ilies Remus
Published: April 2011

This special issue presents eight empirical papers on intra‐individual processes related to employee well‐being in organization with the most of the papers featuring a within‐person approach. The studies examine trajectories of affect, affective predictors of organizational citizenship behavior and creativity, intra‐individual changes in flow at work, and also address longer‐term changes and the role of implicit attitudes. Overall, the studies demonstrate that affective states and well‐being substantially fluctuates within persons, and that these fluctuations are meaningfully related to outcomes that matter for organizations. Copyright © 2011 John Wiley & Sons, Ltd.
Deciphering signals of late Holocene fluvial and aeolian supply from a shelf sediment depocentre off Senegal (north‐west Africa)
Authors: Nizou Jean , Hanebuth Till J.J. , Vogt Christoph
Published: April 2011

High‐resolution climatic records of the late Holocene along the north‐west African continental margin are scarce. Here we combine sediment grain size, elemental distribution and mineral assemblage data to trace dust and riverine sources at a shallow‐marine sediment depocentre in the vicinity of the Senegal River mouth. The aim is to understand how these terrigenous components reflect climate variability during the late Holocene. Major element contents were measured and mineral identification was performed on three sub‐fractions of our sediment core: (i) fluvial material < 2 µm, (ii) aeolian material of 18–63 µm and (iii) a sub‐fraction of dual‐origin material of 2–18 µm. Results show that more than 80% of the total Al and Fe terrigenous bulk content is present in the fluviogenic fraction. In contrast, Ti, K and Si cannot be considered as proxies for one specific source off Senegal. The Al/Ca ratio, recording the continental river runoff, reveals two dry periods from 3010 to 2750 cal a BP and from 1900 to 1000 cal a BP, and two main humid periods from 2750 to 1900 cal a BP and from 1000 to 700 cal a BP. The match between (i) intervals of low river runoff inferred by low Al/Ca values, (ii) reduced river discharge inferred by integrated palynological data from offshore Senegal and (iii) periods of enhanced dune reactivation in Mali confirms this interpretation. Copyright © 2011 John Wiley & Sons, Ltd.
Orthogonal test design for optimization of suitable conditions to separate C‐phycocyanin from Spirulina platensis by high‐speed counter‐current chromatography using reverse micelle solvent system
Authors: Yin Lianhong , Xu Lina , Yu Kun , Zhen Yuhong , Han Xu , Xu Youwei , Qi Yan , Peng Jinyong , Tan Aiping
Published: April 2011

High‐speed counter‐current chromatography (HSCCC) was applied to separate C‐phycocyanin (C‐PC) from Spirulina platensis in the article. The suitable conditions were optimized by an orthogonal test design (L9(3)3), including the stationary phase of reverse micelle solvent system (0.10 g/mL cetyltrimethylammonium bromide [CTAB]/isooctane–hexylalcohol), mobile phase A (0.05 mol/L sodium phosphate buffer, pH 4.0, containing 0.2 mol/L KCl) and mobile phase B (0.05 mol/L sodium phosphate buffer, pH 8.0, containing 0.4 mol/L KCl). Under the selected conditions, 78.7 mg protein was purified from 200 mg crude extract of S. platensis, and the purity of the product was 4.25 based on the absorbance ratio of A620/A280, which was increased 6.85 times compared with the crude extract. Then, the protein was identified to be C‐PC by MALDI‐TOF/TOF‐MS and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) analysis compared with the standard. The application of HSCCC used in the separation of C‐PC from S. platensis was first reported in the article. Furthermore, three kinds of tumor cell lines including human hepatoma cell line SMMC‐7721, human ovarian carcinoma cell line ES‐2, and human lung adenocarcinoma cell line SPCA‐1 were used to evaluate the anticancer activities of the separated product, and the results showed that the separated C‐PC had excellent anti‐tumor actions with the IC50 values at 2.998, 4.854, and 8.423 μg/mL, respectively, for 48 h treatment. The outcome indicates that an effective method for C‐PC purification by HSCCC has been established.
Comparative analysis of radical scavenging and antioxidant activity of phenolic compounds present in everyday use spice plants by means of spectrophotometric and chromatographic methods
Authors: Stankevičius Mantas , Akuņeca Ieva , Jãkobsone Ida , Maruška Audrius
Published: April 2011

Comparative analysis of radical scavenging and antioxidant activities of phenolic compounds present in everyday use spice plants was carried out by means of spectrophotometric and chromatographic methods. Six spice plant samples, namely onion (Allium cepa), parsley (Petroselinum crispum) roots and leaves, celery (Apium graveolens) roots and leaves and leaves of dill (Anethum graveolens) were analyzed. Total amount of phenolic compounds and radical scavenging activity (RSA) was the highest in celery leaves and dill extracts and was the lowest in celery roots. Comparing commonly used spectrophotometric analysis of 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) RSA of extracts with the results obtained using reversed‐phase chromatographic separation with on‐line post‐column radical scavenging reaction detection, good correlation was obtained (R2=0.848). Studies using HPLC system with electrochemical detector showed that bioactive phytochemicals can be separated and antioxidant activities of individual compounds evaluated without the need of a complex HPLC system with reaction detector. The results obtained using electrochemical detection correlate with the RSA assayed using spectrophotometric method (R2=0.893).
Schistosoma mansoni infection in the liver graft: The impact on donor and recipient outcomes after transplantation
Authors: Vincenzi Rodrigo , Neto João Seda , Fonseca Eduardo A. , Pugliese Vincenzo , Leite Katia R. M. , Benavides Marcel R. , Cândido Helry Lopes , Porta Gilda , Miura Irene K. , Pugliese Renata , Danesi Vera B. , Guimarães Teresa C. , Porta Adriana , Kondo Mario , Carone Eduardo , Chapchap Paulo
Published: April 2011

The increasing number of transplants performed each year has led to the identification of unusual diseases in liver grafts from asymptomatic donors that were unrecognized before liver transplantation. Here we report our experience with patients who received liver grafts infected with schistosomiasis. From September 1991 to August 2010, 482 pediatric liver transplants were performed at A. C. Camargo Hospital/Sírio-Libanês Hospital (São Paulo, Brazil). For the identification of Schistosoma mansoni infections, pathology slides for the recipients were reviewed; these included postreperfusion and follow-up liver biopsy samples. We were able to identify 6 cases of schistosomiasis transmitted through infected grafts (5 of these grafts were from living donors). All living donors were confirmed to have normal liver chemistries, negative fecal tests for parasitic diseases, and normal abdominal ultrasound findings. Liver biopsy was not performed before transplantation. In all cases, features of schistosomiasis were absent in the liver explants. The living donors were treated with praziquantel and were taught to avoid risk factors for reinfection. No specific treatment for schistosomiasis was given to the recipients. There were no perioperative deaths, but 2 recipients died after living donor liver transplantation (LDLT) because of Kaposi's sarcoma and non-Hodgkin's lymphoma. In conclusion, using liver grafts infected with S. mansoni eggs did not compromise the results of LDLT in this pediatric cohort. Because of the parasite's life cycle and the therapeutic target of praziquantel, only donors should be treated for the infection. Three years of follow-up showed an uneventful recovery for the living donors.
Factor V Leiden associated with flap loss in microsurgical breast reconstruction
Authors: Khansa Ibrahim , Colakoglu Salih , Tomich David C. , Nguyen Minh‐Doan , Lee Bernard T.
Published: April 2011

Two cases are reported of flap loss following microsurgical perforator flap breast reconstruction in patients diagnosed with a factor V Leiden mutation. Factor V Leiden is the most common inherited cause of hypercoagulability, leading to an increased risk of thrombotic events. The first patient underwent a deep inferior epigastric artery perforator flap and then had recurrent arterial thrombosis both intraoperatively and postoperatively. This patient was subsequently diagnosed with a factor V Leiden mutation. The second patient had a known factor V Leiden mutation and underwent a superior gluteal artery perforator flap, which developed thrombosis and flap loss 2 days later. Preoperative assessment of a personal or family history of unexplained venous or arterial thrombosis should prompt suspicion of a factor V Leiden mutation. This mutation places patients at high risk for thromboembolic events in microvascular breast reconstruction, particularly when oral contraceptives or tamoxifen are used in conjunction. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.
Repair of nerve defect with acellular nerve graft supplemented by bone marrow stromal cells in mice
Authors: Zhao Zhe , Wang Yu , Peng Jiang , Ren Zhiwu , Zhan Shengfeng , Liu Yan , Zhao Bin , Zhao Qing , Zhang Li , Guo Quanyi , Xu Wenjing , Lu Shibi
Published: April 2011

The acellular nerve graft that can provide internal structure and extracellular matrix components of the nerve is an alternative for repair of peripheral nerve defects. However, results of the acellular nerve grafting for nerve repair still remain inconsistent. This study aimed to investigate if supplementing bone marrow mesenchymal stromal cells (MSCs) could improve the results of nerve repair with the acellular nerve graft in a 10‐mm sciatic nerve defect model in mice. Eighteen mice were divided into three groups (n = 6 for each group) for nerve repairs with the nerve autograft, the acellular nerve graft, and the acellular nerve graft by supplemented with MSCs (5 × 105) fibrin glue around the graft. The mouse static sciatic index was evaluated by walking‐track testing every 2 weeks. The weight preservation of the triceps surae muscles and histomorphometric assessment of triceps surae muscles and repaired nerves were examined at week 8. The results showed that the nerve repair by the nerve autografting obtained the best functional recovery of limb. The nerve repair with the acellular nerve graft supplemented with MSCs achieved better functional recovery and higher axon number than that with the acellular nerve graft alone at week 8 postoperatively. The results indicated that supplementing MSCs might help to improve nerve regeneration and functional recovery in repair of the nerve defect with the acellular nerve graft. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.
Tongue reconstruction with the gracilis myocutaneous free flap
Authors: Calabrese Luca , Saito Akira , Navach Valeria , Bruschini Roberto , Saito Noriko , Zurlo Valeria , Ostuni Angelo , Garusi Cristina
Published: April 2011

We describe our experience in tongue reconstruction using the transverse gracilis myocutaneous (TMG) free flap after major demolitive surgery for advanced cancer. This technique was used in 10 patients: seven underwent total glossectomy and three partial glossectomy. In eight patients we performed motor reinnervation attempting to maintain muscular trophism and gain long‐term volumetric stability. The follow‐up period ranged from 6 to 28 months. The overall flap survival was 100%. Nine out of 10 patients resumed oral intake. Our preliminary experience shows that this flap is a good reconstructive option for total glossectomy patients, whereas it is less suited for reconstruction of hemiglossectomy defects. Functional and objective evaluation of the tongue reconstructed with TMG free flap requires further and standardized evaluation. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.