bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B virus‐specific T cell response in chronic hepatitis B patients treated with lamivudine and interferon‐α
Authors: Pontesilli Oscar , Van Nunen Andeltje B. , Van Riel Debby , Carotenuto Patrizia , Niesters Hubert G. , Uytdehaag Fons G. , De Man Robert A. , Osterhaus Albert D. 
Published: July 2004

Abstract: Aims: The goal of the present study was to assess the impact combination antiviral therapy has on immune responses in chronic hepatitis B.Materials and methods: T cell responses were studied in 16 chronically hepatitis B virus (HBV)‐infected patients treated with sequential, partially overlapping, lamivudine‐interferon (IFN)‐α combination therapy.Results: HBcAg‐specific lymphoproliferative response (LPR) was transiently detected in four of five patients who achieved virus suppression (HBV DNA <104 genome equivalents/ml) at end of dual therapy, and then reverted to pre‐treatment viral load after therapy discontinuation. In contrast, no significant HBcAg‐specific LPR was detected in 8 patients who did not attain profound HBV suppression, as well as in three patients who experienced no HBV DNA rebound after therapy discontinuation.Conclusions: This pilot study suggests that restored viral replication after pharmacological suppression drives the immune response to HBV in chronically infected patients. Further characterization of the adaptive immunity and its regulatory mechanisms at time of therapy discontinuation appears therefore necessary in controlled trials.
Increased levels of tissue inhibitor of metalloproteinase‐1 in human hepatocellular carcinoma
Authors: Matsumoto Eiji , Nakatsukasa Harushige , Nouso Kazuhiro , Kobayashi Yoshiyuki , Nakamura Shinichiro , Suzuki Mayumi , Takuma Yoshitaka , Tanaka Hironori , Fujikawa Tatsuya , Shiratori Yasushi 
Published: July 2004

Abstract:  Background: Invasion and metastasis of hepatocellular carcinoma (HCC) are regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, the role of TIMPs in these processes is not clear.Aim: To examine the potential involvement of TIMP‐1 in HCC and the association between TIMP‐1 and clinical outcome of patients with HCC.Methods: The study included 91 patients who underwent surgical removal of HCC. TIMP‐1 concentrations in the supernatant of tissue homogenates of HCC and non‐neoplastic liver were measured by enzyme immunoassay. The relationships between TIMP‐1 concentration and various clinicopathological features and recurrence of HCC after surgical operation were examined.Results: The mean level of TIMP‐1 in HCC (486±610 ng/mg protein, ±SD) was significantly higher than in the non‐neoplastic liver (75±69, P<0.0001). The median level of TIMP‐1 in poorly differentiated HCCs (701 ng/mg protein) was significantly higher than in well‐ (80) and moderately (172) differentiated HCCs (P=0.0047 and P=0.0082, respectively). TIMP‐1 level in liver cirrhosis was higher than in chronic hepatitis (P=0.0015). TIMP‐1 levels in HCC did not influence the recurrence rate of HCC.Conclusions: TIMP‐1 concentration in HCC was higher than in non‐neoplastic liver and correlated with the differentiation grade of HCCs. However, tissue TIMP‐1 concentration does not seem to be an important determinant of HCC recurrence.
Diagnostic and therapeutic implications of bile duct injury in autoimmune hepatitis
Authors: Czaja Albert J. , Muratori Paolo , Muratori Luigi , Carpenter Herschel A. , Bianchi Francesco B. 
Published: July 2004

Abstract: Background: Bile duct injury is not a feature of classical autoimmune hepatitis (AIH), but it has been described in variant forms of the disease.Aims: Our goals were to assess the similarity of AIH with bile duct injury to classical disease and to evaluate the possibility of concurrent primary biliary cirrhosis (PBC).Methods: Fifteen patients with bile duct injury were compared with 151 patients with classical AIH. Patterns of nuclear immunofluorescence and the frequency and nature of autoantibodies associated with AIH and PBC were determined.Results: Patients with bile duct injury had the same nuclear‐staining patterns, frequency and nature of autoantibodies, and genetic risk factors as the comparison group. Features specific for PBC, including the multiple nuclear dot pattern of immunofluorescence and antibodies to the M2 antigens, Sp100 and nuclear pore complex antigen, gp210, did not distinguish them from classical disease. Remission and treatment failure occurred with similar frequencies in both groups.Conclusions: Patients with AIH and bile duct injury lack features of PBC, and they respond as well to corticosteroid therapy as patients with classical disease. Background bile duct changes should not alter the diagnosis or treatment of AIH.
The role of heat shock protein 27 expression in hepatocellular carcinoma in Japan: special reference to the difference between hepatitis B and C
Authors: Harimoto Norifumi , Shimada Mitsuo , Aishima Shin‐ichi , Kitagawa Dai , Itoh Shinji , Tsujita Eiji , Maehara Shin‐ichiro , Taketomi Akinobu , Tanaka Shinji , Shirabe Ken , Maehara Yoshihiko 
Published: July 2004

Abstract:  Background: A recent report showed that heat shock protein (HSP)‐27 expression was related to histological grade and survival of patients with hepatocellular carcinoma (HCC).Aims: The aim of this study was to examine the effect of expression of HSP‐27 on clinicopathological variables in Japanese patients with HCC.Methods: An immunohistochemical study for HSP‐27 was performed on 60 HCC cases using a monoclonal anti‐HSP‐27 antibody. We divided 60 patients into two groups, patients with a low expression of HSP‐27 (n=34) and those with a high expression of HSP‐27 (n=26). Forty patients tested positive for the hepatitis C virus (HCV) antibody and 20 tested positive for the hepatitis B surface antigen.Results: There appeared to be no relationship between HSP expression and clinicopathologic factors and no differences were observed between the high expression group and the low expression group. In the hepatitis B virus (HBV) group (n=20), HSP‐27 expression correlated significantly with prognosis, disease‐free survival (DFS) and overall survival. High expression was significantly associated with poor prognosis in the HBV group. In contrast, patients with a high expression tended to have a good prognosis in the HCV group (n=40): DFS and overall survival.Conclusions: This study showed the possibility that HSP‐27 plays different roles in HBV‐ and HCV‐associated HCCs.
Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock‐out mice and is elevated in murine and human cirrhosis
Authors: Biecker Erwin , Neef Markus , Sägesser Hans , Shaw Sidney , Koshy Abraham , Reichen Jürg 
Published: July 2004

Abstract:  Background: The role of endothelial nitric oxide synthase 3 (NOS‐3) in the hyperdynamic circulation associated with cirrhosis is established but not that of the neuronal (NOS‐1) isoform. We therefore investigated aortic NOS‐1 levels in NOS‐3 knock‐out (KO) and wildtype (WT) mice and in hepatic arteries of patients.Methods: Mice rendered cirrhotic by bile duct ligation (BDL) were compared with sham‐operated controls. Hepatic arteries of cirrhotic patients were collected during liver transplantation; donor vessels served as controls. mRNA levels were quantified by real‐time PCR, protein levels by Western blotting and NO production by Nω‐nitro‐l‐arginine methyl ester inhibitable arginine–citrulline assay.Results: Aortae of NOS‐3 KO mice exhibited higher NOS‐1mRNA (5.6‐fold, P<0.004) and protein levels (8.8‐fold) compared with WT. NO production in aortae of NOS‐3 KO mice was 52% compared with WT (P=0.002). BDL increased NOS‐1 mRNA (2.4‐fold, P=0.01) and protein (7.1‐fold) levels in aortae of WT, but no further in the NOS‐3 KO mice. Hepatic artery NOS‐1 mRNA levels in cirrhotic patients were markedly increased compared with controls (24.5‐fold, P=0.0007).Conclusions: Increased NOS‐1 mRNA and protein levels and partially maintained in vitro NO‐production in aortae of NOS‐3 KO mice suggest that NOS‐1 may partially compensate for NOS‐3 deficiency. BDL‐induced increase in aortic NOS‐1 mRNA and protein levels hint that not only NOS‐3, but also NOS‐1 may be involved in the regulation of systemic hyperdynamic circulation and portal hypertension. Upregulation of NOS‐1 mRNA levels in hepatic arteries of portal hypertensive patients suggests possible clinical significance for these experimental findings.
Analysis of the functional integrity of cryopreserved human liver cells including xenografting in immunodeficient mice to address suitability for clinical applications
Authors: Cho Jae‐Jin , Joseph Brigid , Sappal Baljit Singh , Giri Ranjit K. , Wang Richard , Ludlow John W. , Furth Mark E. , Susick Robert , Gupta Sanjeev 
Published: July 2004

Abstract: Background: The availability of well‐characterized human liver cell populations that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after cryopreservation and engraft in immunodeficient mice.Methods: We isolated cells from discarded human livers and studied the properties of cryopreserved cells. The viability of thawed cells was established with multiple in vitro assays, including analysis of liver gene expression, ureagenesis, cytochrome P450 activity, and growth factor‐induced cell proliferation. The fate of transplanted cells was analysed in immunodeficient NOD‐SCID mice.Results: After thawing, the viability of human hepatocytes exceeded 60%. Cells attached to culture dishes, proliferated following growth factor stimulation and exhibited liver‐specific functions. After transplantation in NOD‐SCID mice, cells engrafted in the peritoneal cavity, a heterologous site, as well as the liver itself, retained hepatic function and proliferated in response to liver injury. Transplanted hepatocytes were integrated in the liver parenchyma. Occasionally, transplanted cells were integrated in bile ducts.Conclusions: Cryopreserved human liver cell showed the ability to retain functional integrity and to reconstitute both hepatic and biliary lineages in mice. These studies offer suitable paradigms aimed at characterizing liver cells prior to transplantation in people.
Inhibition of tumor necrosis factor‐induced apoptosis in transgenic mouse liver expressing creatine kinase
Authors: Hatano Etsuro , Tanaka Akira , Kanazawa Akiyoshi , Tsuyuki Shigeru , Tsunekawa Shoji , Iwata Shingo , Takahashi Rei , Chance Britton , Yamaoka Yoshio 
Published: July 2004

Abstract: Background: The mitochondrion acts as a pivotal decision center in many types of apoptotic responses. To clarify the effects of the enhanced mitochondrial function on tumor necrosis factorα (TNFα)‐induced apoptosis, we studied hepatic injuries in transgenic mice whose livers express creatine kinase (CK).Methods: Mice fed a diet containing 10% creatine, came to accumulate phosphocreatine and to enhance hepatic ATP levels and mitochondrial oxidative phosphorylation activities. TNFα‐mediated hepatic apoptosis in normally fed and Cr‐feeding CK transgenic mice were assessed.Results: TNFα and actinomycin D cause severe liver failure in normally fed transgenic mice, and in the wild‐type mice. In contrast, no significant elevations in transaminase levels after injection were observed in Cr feeding transgenic mice. The disruption of the mitochondrial transmembrane potential at 2 h after TNFα injection, prior to ATP depletion, activation of caspase 3 like protease, and DNA fragmentation at 4–6 h after injection, were observed in normally fed transgenic mice. These were fully suppressed in Cr feeding transgenic mice. However, anti‐Fas antibody‐induced apoptosis was not inhibited in both groups.Conclusions: The results indicate that TNFα‐induced apoptosis was inhibited in CK transgenic mice livers by maintaining mitochondrial function.
Magnetic Resonance Imaging: Significance of Early Ischemic Changes on Computed Tomography
Authors: Derex Laurent , Nighoghossian Norbert , Hermier Marc , Pialat Jean-Baptiste , Wiart Marlène , Philippeau Frédéric , Adeleine Patrice , Honnorat Jérôme , Froment Jean-Claude , Berthezène Yves , Trouillas Paul 
Published: July 2004

The significance of early ischemic changes (EICs) on CT remains controversial. MRI may provide relevant information in patients with EICs. <i>Methods:</i> EICs were assessed in patients with acute ischemic stroke. MRI was promptly performed at presentation after CT and repeated on day 1. The relationship between EICs and MRI parameters was assessed with one-way ANOVA for analysis of continuous variables and by the χ<sup>2</sup> test for the analysis of variables with a binary outcome. <i>Results:</i> Fourty-eight patients underwent CT and MR imaging before treatment with recombinant tissue plasminogen activator (age: 63 ± 14 years). EICs were graded as absent in 28 patients, <33% in 15 patients, and >33% of the middle cerebral artery (MCA) territory in 5 patients. NIHSS score was higher in patients with EICs that covered more than one third of the MCA territory (19 ± 3) compared to those without EICs (12 ± 5; p = 0.04). Patients who had major EICs had a larger acute lesion volume in diffusion-weighted imaging (DWI; 140 ± 78 cm<sup>3</sup>) compared to those without EICs (33 ± 51 cm<sup>3</sup>, p < 0.0001). Regional cerebral blood flow, regional cerebral blood volume, time to peak and mean transit time values were not significantly different in the study groups. <i>Conclusion:</i> EICs reflect mainly a larger DWI lesion.
Sputum Levels of Reduced Glutathione Increase 24 Hours after Allergen Challenge in Isolated Early, but Not Dual Asthmatic Responders
Authors: Beier Jutta , Beeh Kai Michael , Semmler David , Buhl Roland 
Published: July 2004

<i>Background:</i> The pathogenesis of late asthmatic reactions after allergen challenge in contrast to isolated early responses is incompletely understood. Recently, the antioxidant glutathione and endogenous nitrosothiols were shown to protect against bronchoconstriction. We compared reduced (GSH) and oxidized glutathione (GSSG) and nitrosothiols in induced sputum following allergen challenge in mild asthmatics with isolated early (EAR) and dual early and late (LAR) asthmatic responses. <i>Methods:</i> Exhaled nitric oxide, sputum cells and sputum supernatant concentrations of GSH, GSSG and nitrosothiols were quantified 2–5 days prior to and 24 h after allergen challenge in 24 mild asthmatics (12 EAR, 12 LAR, only beta-agonists prn). <i>Results:</i> There were no differences at baseline between EAR and LAR asthmatics for any of the parameters (p > 0.1, all comparisons). Mean ± SD fall in forced expiratory volume in 1 s, expressed as the percentage decrease compared to the baseline value, between 3 and 8 h after allergen challenge was 1 ± 5% in the group of patients without LAR vs. 24.9 ± 8.7% in the group of patients with LAR (p < 0.001). Sputum eosinophils increased in both groups (p < 0.05, both comparisons), whereas neutrophils only increased in LAR subjects (p = 0.06 vs. EAR). In contrast, GSH was significantly increased 24 h after challenge only in EAR asthmatics [geometric mean with 95% confidence intervals: before: 3.3 µ<i>M</i> (1.25–7.9 µ<i>M</i>), after: 5.9 µ<i>M</i> (2.7–12.9 µ<i>M</i>), p = 0.05; mean difference vs. LAR subjects: 6 µ<i>M</i> (0.1–12 µ<i>M</i>), p = 0.048], and the proportion of GSSG was positively correlated with postallergen eosinophils in all patients (rho = 0.4, p = 0.05). There was no change in nitrosothiols after 24 h in either EAR or LAR subjects (p > 0.23, all comparisons). <i>Conclusions:</i> GSH increases 24 h after allergen challenge in isolated early responders. These data suggest that different adoptive responses to allergen may result in different physiologic phenotypes. Further studies on the role of glutathione in allergen-induced bronchoconstriction are clearly warranted.
Antimonocyte Chemoattractant Protein-1 Gene Therapy Attenuates Graft Vasculopathy
Authors: Saiura Akio , Sata Masataka , Hiasa Ken-ichi , Kitamoto Shiro , Washida Miwa , Egashira Kensuke , Nagai Ryozo , Makuuchi Masatoshi 
Published: July 2004

Objective—Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis.Methods and Results—We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79±0.05 versus 0.48±0.04).Conclusions—The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.
The Portable Bullhe Shah: Biography, Categorization, and Authorship in the Study Of Punjabi Sufi Poetry
Authors: Rinehart Robin 
Published: July 2004

AbstractThe Punjabi poet Bullhe Shah (1680-1758) is revered by Muslims, Hindus and Sikhs. In the extensive body of interpretive literature devoted to his life and work, scholars have contested his religious identity, characterizing Bullhe Shah in various ways, e. g. as a Sufi, a Vedantic Sufi, or a Vai ava Vedantic Sufi. This article examines the nature of the debates about Bullhe Shah's identity, and how these debates have shaped the varying portrayals of Bullhe Shah's life, the corpus of his poetry, and the characterization of his religious affiliation. I argue that a series of unexamined assumptions — about the nature of biography and its relation to the development of a worldview, about the categorization of religious identity, and about the nature of authorship — have created these conflicting portrayals of the poet and his work, making Bullhe Shah a kind of "portable" figure who is placed in widely divergent contexts. I conclude by arguing that Bullhe Shah's portability, or his placement within different contexts (for different purposes), is itself a useful topic for analysis, and provides the basis for a potentially more fruitful study not only of Bullhe Shah's life and work, but also of his audiences and their responses to him.
The Irony of Romans 13
Authors:   Carter
Published: July 2004

AbstractThis article explores the possibility that Paul was using irony in his commendation of the state in Romans 13. It is proposed that the original audience of the letter shared with Paul a common experience of oppression at the hands of the authorities and were aware of the abuses that took place in the opening years of Nero's reign. The consequent implausibility of Paul's language would have alerted his readers to the presence of irony. They would have been able to set aside the surface meaning of the discourse and to recognise that Paul was using the established rhetorical technique of censuring with counterfeit praise. While the passage can be read as a straightforward injunction to submit to the authorities, an ironic reading of the text results in a subversion of the very authorities it appears to commend.
Die korinthische Gemeinde als Nebenadressat des Römerbriefs. Eigentextreferenzen des Paulus und Kommunikativer Kontext des längsten Paulusbriefes
Authors: Hartwig Charlotte , Theißen Gerd 
Published: July 2004

AbstractThe letter to the Romans is not only addressed to the Romans as the main addressees but indirectly to the Corinthians. When Paul was writing this letter he lived in the Corinthian congregation, continuing his dialogue with the Corinthians. This is why Paul reworked some topics from 1 and 2 Corinthians in order to correct them and to put them more exactly. The letter is thus embedded in his written and oral communication with the Corinthians. The Corinthians could understand some hints and allusions much better than the Romans.
Mt. 17:1-9 in 'Codex Schøjen'
Authors: Baarda Tjitze 
Published: July 2004

AbstractThe magnificent edition of a new Middle-Egyptian Coptic text of Matthew (Codex Schøjen), published by the late Hans-Martin Schenke, is an unexpected contribution to New Testament scholarship. Its text differs in many respects from all later Coptic versions including the famous Codex Scheide, published by the same author, which was written in the same dialect. This new and certainly most intriguing text requires a diligent investigation by textual critics in view of the far-reaching conclusions which Professor Schenke drew from its textual character. Only a thorough investigation of Matthew's text as far as it is preserved in this codex will enable textual critics to give a final and fair judgment of Schenke's hypotheses. This contribution can only be a first step to reach such a judgment.
Kaolin polytype evidence for a hot-fluid pulse along Caledonian thrusts during rifting of the European Margin
Authors: Parnell J. , Watt G. , Chen H. , Wycherley H. , Boyce A. , Elmore D. , Blumstein R. , Engel M. , Green P. 
Published: July 2004

AbstractSedimentary basins developed along the European margin during the earliest, Permian, stage of proto-Atlantic rifting, during a phase of high heat flow. The proximity of some basins to Caledonian thrusts has implied that rifts locally utilized the basement fabric. New mineralogical and palaeomagnetic data show that thrust planes in the Moine Thrust Zone channelled a pulse of hot fluid in Permian time. The fluids precipitated kaolin in fractures in the thrust zone, and with decreasing intensity away from the zone. The high-temperature polytype dickite is largely confined to major thrust planes. Stable H and O isotope analyses indicate that the parent fluid included meteoric water involved in a hydrothermal system. Coeval hydrothermal hematite has a chemical remanence that dates the fluid pulse as Permian. This is direct evidence for post-orogenic activity in the thrust zone, in which the thrusts vented excess heat during regional crustal extension. The example from the European margin exemplifies the importance of deep-seated structures in the release of heat, and the value of kaolinite polytype mapping as a tool to record anomalous palaeo-heat flow.