bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process
Authors: Narayanaswamy Bommayya , Gonde Christopher , Tredger Michael J. , Hussain Munther , Vergani Diego , Davenport Mark 
Published: June 2007

Abstract

Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intra- and extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4+ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measurable inflammatory component longitudinally by studying a panel of cellular adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]) and soluble proinflammatory mediators (T helper 1 [interleukin {IL}-2 and interferonγ] and T helper 2 [IL-4 and IL-10]) cytokines and macrophage markers (tumor necrosis factor [TNF] α and IL-18) in 21 consecutive infants with BA post-Kasai portoenterostomy (KP). The levels of all adhesion molecules and cytokines (except IL-10) increased progressively by 6 months post-portoenterostomy. The response was non-polarized but with 100-fold increases in IL-2, TNFα and IL-18 particularly but only modest elevations in IL-10. When proinflammatory profiles were related to outcome, we found poor discrimination if assessed as clearance of jaundice but markedly higher values for IL-2, interferonγ, IL-4, IL-10, TNFα and sICAM-1 for those who would be transplanted by 1 year. Using ROC curve analysis for sICAM-1 levels at 1 month post-KP, a cutoff level of 1,779 ng/ml was determined to predict the need for transplantation at 1 year with 92% specificity and 87% sensitivity.

Conclusion:

The early circulating inflammatory process in BA is persistent, progressive and involves a non-polarized T cell, macrophage and cell adhesion molecule response only partially ameliorated by KP. (HEPATOLOGY 2007;46:180–187.)
Hippocampus modulates the behaviorally‐sensitizing effects of nicotine in a rat model of novelty‐seeking: Potential role for mossy fibers
Authors: Bhatti Amrinder S. , Hall Penny , Ma Zhiyuan , Tao Rui , Isgor Ceylan 
Published: June 2007

AbstractPresent experiments investigate interactions between a rat model of the novelty‐seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally‐sensitizing effects of NIC. Outbred rats were phenotype‐screened as high‐responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low‐responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3‐d intervals on postnatal days 33–44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra‐pyramidal mossy fiber (SP‐MF) terminal field. The increase in the SP‐MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC‐induced locomotion and the SP‐MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC. © 2007 Wiley‐Liss, Inc.
Consistent expression of the stem cell renewal factor BMI‐1 in primary and metastatic melanoma
Authors: Mihic‐Probst Daniela , Kuster Ariana , Kilgus Sandra , Bode‐Lesniewska Beata , Ingold‐Heppner Barbara , Leung Carly , Storz Martina , Seifert Burkhardt , Marino Silvia , Schraml Peter , Dummer Reinhard , Moch Holger 
Published: June 2007

AbstractStem cell‐like cells have recently been identified in melanoma cell lines, but their relevance for melanoma pathogenesis is controversial. To characterize the stem cell signature of melanoma, expression of stem cell markers BMI‐1 and nestin was studied in 64 cutaneous melanomas, 165 melanoma metastases as well as 53 melanoma cell lines. Stem cell renewal factor BMI‐1 is a transcriptional repressor of the Ink4a/Arf locus encoding p16ink4a and p14Arf. Increased nuclear BMI‐1 expression was detectable in 41 of 64 (64%) primary melanomas, 117 of 165 melanoma metastases (71%) and 15 of 53 (28%) melanoma cell lines. High nestin expression was observed in 14 of 56 primary melanomas (25%), 84 of 165 melanoma metastases (50%) and 21 of 53 melanoma cell lines (40%). There was a significant correlation between BMI‐1 and nestin expression in cell lines (p = 0.001) and metastases (p = 0.02). These data indicate that cells in primary melanomas and their metastases may have stem cell properties. Cell lines obtained from melanoma metastases showed a significant higher BMI‐1 expression compared to cell lines from primary melanoma (p = 0.001). Further, primary melanoma lacking lymphatic metastases at presentation (pN0, n = 40) was less frequently BMI‐1 positive than melanomas presenting with lymphatic metastases (pN1; n = 24; 52% versus 83%; p = 0.01). Therefore, BMI‐1 expression appears to induce a metastatic tendency. Because BMI‐1 functions as a transcriptional repressor of the Ink4a/Arf locus, p16ink4a and p14Arf expression was also analyzed. A high BMI‐1/low p16ink4a expression pattern was a significant predictor of metastasis by means of logistic regression analysis (p = 0.005). This suggests that BMI‐1 mediated repression of p16ink4a may contribute to an increased aggressive behavior of stem cell‐like melanoma cells. © 2007 Wiley‐Liss, Inc.
Gossypol reduction of tumor growth through ROS‐dependent mitochondria pathway in human colorectal carcinoma cells
Authors: Ko Ching‐Huai , Shen Shing‐Chuan , Yang Liang‐Yo , Lin Cheng‐Wei , Chen Yen‐Chou 
Published: June 2007

AbstractAmong 13 different cell lines, gossypol (GOS) showed the most potent cytotoxic effect against human colorectal carcinoma cells including HT29, COLO205, COLO320HSR and COLO320DM cells according to an MTT assay. The cytotoxic effect of GOS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in both COLO205 and HT29 cells. Activation of caspase 3, 6, 8 and 9, but not caspase 1, accompanied by the appearance of cleaved fragments of PARP (85 kDa), and caspase 3 (p17/p15), was identified in GOS‐treated cells. Decreases in Bcl‐xL and phosphorylated Bad proteins were found in GOS‐treated cells. GOS induction of ROS production was detected by in vitro plasmid digestion, and an increase in the intracellular peroxide level was observed in GOS‐treated COLO205 cells by the DCHF‐DA assay. Antioxidants including N‐acetyl‐L‐cysteine (NAC), catalase (CAT), tempol (TEM) and melatonin (MEL), but not allopurinol (ALL), pyrrolidine dithiocarbamate (PDTC) or diphenylene iodonium (DPI), significantly inhibited GOS‐induced Reactive oxygen species (ROS) production through blocking the occurrence of apoptosis. GOS induced mitochondrial dysfunction characterized by a loss of the mitochondria membrane potential via DiOC6 staining, and the release of cytochrome c (Cyt c) and apoptosis‐inducing factor (AIF) from mitochondria to the cytoplasm was observed. Removing mitochondria by ethidium bromide (EtBr) treatment significantly reduced the apoptotic effect of GOS in COLO205 cells. Furthermore, an intraperitoneal injection of GOS or gossypol acetic acid (GAA) significantly reduced the growth of colorectal carcinoma induced by a subcutaneous injection of COLO205 cells in nude mice. Results of the present study provide the first evidences demonstrating the in vitro and in vivo antitumor effects of GOS via an ROS‐dependent mitochondrial apoptosis in colorectal carcinoma. © 2007 Wiley‐Liss, Inc.
In vitro and in vivo evaluation of intrinsic immunogenicity of reporter and insulin gene therapy plasmids
Authors: Ratanamart Jarupa , Huggins Christopher G. , Kirby John A. , Shaw James A. M. 
Published: June 2007

AbstractBackgroundPlasmid DNA vectors offer the potential of safe gene therapy avoiding viral vector‐mediated toxicity and immunogenicity. As plasmid DNA is bacterial in origin, presence of bacterial lipopolysaccharide (LPS) or unmethylated CpG dinucleotides may stimulate host innate immunity.MethodsPrimary cultures of mouse and rat dendritic cells were established and incubated with bacterial lipopolysaccaride; immunostimulatory CpG oligodeoxynucleotide; control GpC oligodeoxynucleotide; and a range of (pVR1012) plasmids encoding transgenes with increasing CpG content (wild‐type and mutant human preproinsulin; non‐mammalian eukaryotic eGFP reporter gene; and bacterial β‐galactosidase reporter gene). IL‐12 secretion was assayed to determine in vitro plasmid immunogenicity. Local inflammatory response following intramuscular injection of these plasmids, with or without a non‐ionic carrier SP1017, was characterised in vivo.ResultsDose‐responsive LPS and CpG stimulation of IL‐12 secretion from dendritic cells was demonstrated. All plasmids induced significant IL‐12 secretion in comparison to control unstimulated cells. The β‐galactosidase plasmid had highest CpG content and induced significantly higher IL‐12 secretion than constructs containing a eukaryotic transgene. Injection of rat muscle with the β‐galactosidase construct induced greater inflammatory response than human preproinsulin constructs. This was further enhanced by SP1017. At 2 days post‐injection, monocyte/macrophage injection site infiltration predominated with CD8‐positive lymphocytes predominating at 7 days. There was no evidence of transgene expression in infiltrating immune cells.ConclusionsDendritic cell immunostimulation may be employed as an in vitro bioassay of innate immune response to plasmid DNA vectors during evaluation for clinical gene therapy. Copyright © 2007 John Wiley & Sons, Ltd.
Hepatitis C virus infection and genotypes in Antananarivo, Madagascar
Authors: Razafindratsimandresy Richter , Dubot Audrey , Ramarokoto Charles‐Emile , Iehlé Catherine , Soares Jean‐Louis , Rousset Dominique 
Published: June 2007

AbstractThe prevalence of hepatitis C virus (HCV) genotypes in Madagascar is not well known. Serum samples were obtained from 2,169 individuals selected by random sampling in the population living in Antananarivo city. Using HCV antibody test (Monolisa anti‐HCV Plus version 2), 36 (1.7%) of the 2,169 samples were positive. The presence of HCV RNA was determined by using reverse transcription polymerase chain reaction amplifying the 5′‐untranslated region (UTR): HCV RNA was detected in 17 of the 36 HCV antibodies positive samples. The genotype was determined using BLAST tool with another 5′‐UTR fragment. The phylogenetic analysis of the polymerase (NS5b) and envelope (E1/E2) fragment sequences showed a low level of diversity compared to the high diversity in other African countries: subtype 1b (nine cases, 52.9%) and genotype 2 (eight cases, 47.1%) including subtype 2b (six cases), subtype 2k (one case), and one unclassified subtype. BLAST search with the 5′‐UTR fragment sequence of this unclassified subtype identified that strain as subtype 2a. J. Med. Virol. 79: 1082–1088, 2007. © 2007 Wiley‐Liss, Inc.
Verses, viruses, and the vulnerability of the blood supply in industrialized countries
Authors: Mushahwar Isa K. 
Published: June 2007

AbstractIn the last 30 years, tremendous progress in identifying transfusion‐transmitted viruses such as HBV, HCV, and HIV in industrialized countries has been achieved. Currently, the residual risk of transmitting these viruses through transfusion is very low especially after the introduction of “minipool” nucleic acid‐amplification tests. Despite these major technical advances, there remains a legitimate concern as to the transmission of other blood‐borne infectious agents through blood transfusion. Among these agents are HBV mutants, occult HBV, and HCV infections, malaria, Chagas, West Nile, dengue, and vesiviruses, bacterial infections such asYersinia enterocolitica, and tick borne diseases such as human monocytic ehrlichiosis, human granulocytic ehrlichiosis, Rocky Mountain spotted fever, and Lyme and prion diseases such as Creutzfeldt and variant Creutzfeldt. Most of these agents are very rarely transmitted by transfusion in industrialized countries. However, an awareness of their possible transmission is essential for the control of spread of these diseases among the public by human‐to‐human transmission via blood transfusion. This review summarizes the current status of prevalence and diagnosis of these emerging diseases and also updates our knowledge on recently discovered non‐pathogenic blood‐borne viruses such as GB virus C and Torque Tenoviruses. J. Med. Virol. 79: 1229–1237, 2007. © 2007 Wiley‐Liss, Inc.
Prolonged‐interferon therapy reduces hepatocarcinogenesis in aged‐patients with chronic hepatitis C
Authors: Arase Yasuji , Ikeda Kenji , Suzuki Fumitaka , Suzuki Yoshiyuki , Kobayashi Masahiro , Akuta Norio , Hosaka Tetsuya , Sezaki Hitomi , Yatsuji Hiromi , Kawamura Yusuke , Kobayashi Mariko , Kumada Hiromitsu 
Published: June 2007

AbstractThe aim of this study was to elucidate the reduction of hepatocarcinogenesis by prolonged interferon (IFN) monotherapy in aged chronic hepatitis C patients. Inclusion criteria were biopsy‐proven chronic hepatitis or liver cirrhosis, 60 years and over, elevated serum aminotransferase and positive hepatitis C virus (HCV)‐RNA. One hundred and twenty patients satisfied the above criteria were treated with natural IFN‐alpha (dose: 3 million unit (MU), two or three times weekly for 0.5–15.5 years, mean 2.47 years) (IFN group). Another 240 patients treated with herbal medicines excluding IFN were selected as control (no‐IFN group). The patients not treated with IFN were matched 2:1 with IFN group patients for sex and age. The clinical and biological differences were compared after treatment with the IFN group and the untreated group. Serum alpha‐fetoprotein (AFP) level decreased with statistical significance after initiation of treatment with IFN compared to no treatment. The 5‐ and 10‐year cumulative rates of hepatocellular carcinoma (HCC) were 5.9 and 13.7%, and 17.1 and 32.8%, for the IFN and untreated group, respectively. HCC development occurred when histologic staging was advanced, and IFN was not given, the AFP level after treatment was >10 ng/ml. Cox regression analysis indicated that the relative risk of HCC in patients in the IFN group was 0.3 times of that in the untreated patients. The relative risk rate for HCC in severe fibrosis was 3.9 compared with mild or moderate fibrosis. In conclusion, long‐term IFN therapy for aged patients with chronic HCV infection is effective in decreasing the serum AFP level and preventing hepatocarcinogenesis. J. Med. Virol. 79: 1095–1102, 2007. © 2007 Wiley‐Liss, Inc.
Virological characterization of patients treated early is able to control HIV‐1 replication after multiple cycles of structured therapy interruption
Authors: Rozera G. , Abbate I. , D'Offizi G. , Corpolongo A. , Narciso P. , Vlassi C. , Martini F. , Calcaterra S. , Capobianchi M.R. 
Published: June 2007

AbstractThis study aimed to define clinical and virological parameters associated with spontaneous control of HIV replication in patients having initiated HAART during primary HIV infection, who underwent structured therapy interruption by two protocols with either fixed or HIV viremia‐guided scheme. At the end of the protocol all patients were changed to viremia‐guided scheme and observed for 12 months (follow‐up). Patients maintaining HIV viremia below the indications for resumption of HAART during the follow‐up, were defined controllers, those who had to resume HAART were defined non‐controllers. The following parameters were examined: pre‐interruption therapy duration, CD4+, HIV RNA, proviral DNA, evolution of viral quasispecies. No specific advantage was conferred by either interruption of structured therapy in the proportion of controllers and non‐controllers. Pre‐HAART and zenith CD4+, pre‐therapy interruption, HAART duration, but not pre‐HAART HIV RNA, were significantly higher in controllers as compared to non‐controllers. HIV RNA levels after the first interruption cycle of therapy were significantly lower in controllers than in non‐controllers. Proviral DNA levels were also lower in controllers at this time point. HIV RNA and proviral DNA levels associated with the last interruption of therapy cycle were not different from those associated with the first cycle, and, in spite of multiple waves of virus rebound, very few gag quasispecies variants emerged in each patient. The data suggest that pre‐treatment clinical parameters and virological events associated with the first viral rebound are crucial factors in determining the ability to control viral replication after multiple cycles of interruption of treatment. J. Med. Virol. 79: 1047–1054, 2007. © 2007 Wiley‐Liss, Inc.
Prevalence of X4 tropic HIV‐1 variants in patients with differences in disease stage and exposure to antiretroviral therapy
Authors: Poveda Eva , Briz Verónica , de Mendoza Carmen , Benito José Miguel , Corral Angélica , Zahonero Natalia , Lozano Sara , González‐Lahoz Juan , Soriano Vincent 
Published: June 2007

AbstractViral tropism plays an important role in HIV pathogenesis. However, its correlation with the clinical outcome and following exposure to antiretroviral drugs are still unclear. HIV‐1 co‐receptor usage was examined in 206 infected individuals: 67 seroconverters, 52 chronically drug‐naïve, and 87 antiretroviral‐experienced patients. The V3 loop was sequenced from plasma HIV‐RNA and co‐receptor usage was inferred using a phenotype predictor software (http://genomiac2.ucsd.edu:8080/wetcat/v3.html), which classifies V3 sequences as R5 or X4. The overall prevalence of X4 viruses was 26.2%, with significant differences among groups: 13.4% in seroconverters, 25% in drug‐naïve, and 36.8% in antiretroviral‐ experienced patients (P = 0.001). The presence of X4 variants in the latter group was associated with higher viral load (P = 0.002) but not with lower CD4 counts. There was no association between HIV tropism and gender, transmission route or age. Neither with the CCR5 Δ32 genotype. Moreover, no association was found between HIV‐1 tropism and drug resistance mutations nor with failure to regimens based on either protease inhibitors or non‐nucleoside reverse transcriptase inhibitors. Finally, no significant association was found between IL‐7 plasma levels with HIV‐1 tropism. In summary, X4 viruses are particularly frequent among antiretroviral‐experienced patients with high viral loads, irrespective of the CD4 count. Thus, CCR5 antagonists should be used with special caution in this subset of patients. J. Med. Virol. 79: 1040–1046, 2007. © 2007 Wiley‐Liss, Inc.
Hepatitis C virus expression and interferon antiviral action is dependent on PKR expression
Authors: Tokumoto Yoshio , Hiasa Yoichi , Horiike Norio , Michitaka Kojiro , Matsuura Bunzo , Chung Raymond T. , Onji Morikazu 
Published: June 2007

AbstractInterferon (IFN)‐inducible double‐stranded RNA‐activated protein kinase (PKR) is thought to play a key antiviral role against hepatitis C virus (HCV). However, demonstrating the importance of PKR expression on HCV protein synthesis in the presence or absence of IFN has proven difficult in vivo. In the present experiment, full‐length HCV constructs were transiently transfected into two cell lines stably expressing T7 RNA polymerase. HCV expression was monitored under conditions of upregulated or downregulated PKR expression. In addition, IFN was monitored during downregulation of PKR. HCV expression effectively increased PKR expression, as well as that of its regulated proteins. PKR was obviously knocked down by PKR‐specific siRNA, which resulted in significantly increased HCV core protein levels. Conversely, over‐expression of PKR significantly suppressed HCV core levels in both cell lines. Furthermore, IFN induced high levels of PKR, whereas downregulation of PKR reversed IFN's antiviral effects and increased HCV core levels. Based on these results, it appears that HCV protein expression is directly dependent on PKR expression. PKR is antiviral toward HCV and responsible for IFN's effect against HCV. J. Med. Virol. 79: 1120–1127, 2007. © 2007 Wiley‐Liss, Inc.
Prediction of the efficacy of antiviral therapy for hepatitis C virus infection by an ultrasensitive RT‐PCR assay
Authors: Kinai Ei , Hanabusa Hideji , Kato Shingo 
Published: June 2007

AbstractThe efficacy of interferon therapy for hepatitis C virus (HCV) infection improved remarkably. However, virologic relapse occurs in a substantial proportion of patients with virologic response (defined as an HCV RNA level below 50 IU/ml at the end‐of‐treatment). A highly sensitive RT‐nested PCR assay capable of detecting almost a single copy of HCV RNA and a real‐time RT‐PCR assay to quantify HCV RNA down to 120 copies per ml were developed. The RT‐nested PCR assay showed that 1 IU of HCV RNA is equivalent to 12.2 copies. For 28 patients with virologic response (12 relapsers and 16 sustained virologic responders), week‐4 and end‐of‐treatment plasma samples were retested. At week 4, HCV RNA was detected by the RT‐nested PCR and qualitative COBAS Amplicor HCV version 2.0 in 8/9 (89%) and 6/9 (67%) samples from relapsers, and in 4/16 (25%) and 2/16 (13%) samples from sustained virologic responders, respectively. End‐of‐treatment samples with HCV‐negative by the qualitative COBAS Amplicor were positive by the present assay in 4/12 (25%) of relapsing patients and 0/16 (0%) of sustained virologic responders. The viral levels detected by the present assay in the Amplicor‐negative samples were 3.5–17.3 copies/ml, which is below the detection limit of COBAS Amplicor. In conclusion, the highly sensitive RT‐nested PCR assay can predict sustained virologic response at week 4 and virologic relapse at the end‐of‐treatment more accurately than COBAS Amplicor, suggesting its usefulness in monitoring antiviral therapy for HCV infection. J. Med. Virol. 79: 1113–1119, 2007. © 2007 Wiley‐Liss, Inc.