bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic abnormalities in patients with chronic granulomatous disease
Authors: Hussain Nadeem , Feld Jordan J. , Kleiner David E. , Hoofnagle Jay H. , Garcia-Eulate Reyes , Ahlawat Sushil , Koziel Deloris E. , Anderson Victoria , Hilligoss Dianne , Choyke Peter , Gallin John I. , Liang Jake T. , Malech Harry L. , Holland Steven M. , Heller Theo 
Published: February 2007

Abstract

Chronic granulomatous disease (CGD) is a rare congenital disorder characterized by repeated bacterial and fungal infections. Aside from a high incidence of liver abscess, little is known about hepatic involvement in CGD. The aim of this study was to describe the spectrum of liver abnormalities seen in CGD. The charts of 194 patients with CGD followed at the NIH were reviewed, with a focus on liver abnormalities. Liver enzyme elevations occurred on at least one occasion in 73% of patients during a mean of 8.9 years of follow-up. ALT elevations were generally transient. Although transient alkaline phosphatase (ALP) elevations were also common, persistent ALP elevations lasting up to 17.6 years were seen in 25% of patients. Liver abscess occurred in 35% of patients. Drug-induced hepatotoxicity was documented in 15% of patients but likely occurred more frequently. Hepatomegaly was found in 34% and splenomegaly in 56% of patients. Liver histology showed granulomata in 75% and lobular hepatitis in 90% of specimens. Venopathy of the portal vein was common (80%) and associated with splenomegaly. Venopathy of the central vein was also common (63%) and was associated with the number of abscess episodes. Nodular regenerative hyperplasia (NRH) was seen in 9 patients, including 6 of 12 autopsy specimens.

Conclusion:

Liver enzyme abnormalities occur frequently in patients with CGD. In addition to liver abscesses and granulomata, drug hepatotoxicity is likely underappreciated. Vascular lesions such as venopathy and—to a lesser extent—NRH are common. The cause and clinical consequences of venopathy await prospective evaluation. (Hepatology 2007;45:675–683.)
Prevention of hepatocyte allograft rejection in rats by transferring adenoviral early region 3 genes into donor cells
Authors: Mashalova Elena V. , Guha Chandan , Roy-Chowdhury Namita , Liu Laibin , Fox Ira J. , Roy-Chowdhury Jayanta , Horwitz Marshall S. 
Published: February 2007

Abstract

Hepatocyte transplantation is being evaluated as an alternative to liver transplantation for metabolic support during liver failure and for definitive treatment of inherited liver diseases. However, as with liver transplantation, transplantation of allogeneic hepatocytes requires prolonged immunosuppression with its associated untoward effects. Therefore, we explored strategies for the genetic modification of donor hepatocytes that could eliminate allograft rejection, obviating the need for immunosuppression. Products of early region 3 (

AdE3

) of the adenoviral genome are known to protect infected cells from immune recognition and destruction. In the present study we showed that immortalized rat hepatocytes that had been stably transduced with AdE3 before transplantation into fully MHC-mismatched rats are protected from allograft rejection. Quantitative real-time PCR analysis showed that a similar number of engrafted AdE3-transfected hepatocytes had survived in syngeneic and allogeneic recipients. AdE3 expression did not reduce expression of MHC class I on the surfaces of donor hepatocytes. Consistent with this, the

in vivo

cytotoxic cell–mediated alloresponse was attenuated but not abolished in recipients of AdE3-transfected allogeneic hepatocytes. In contrast, graft survival correlated with a marked reduction in cell-surface localization of Fas receptor in the transplanted cells and inhibition of Fas-mediated apoptosis, which are related to the antiapoptotic functions of the AdE3 proteins.

CONCLUSION:

AdE3

gene products prevent hepatocyte allograft rejection mainly by protecting the cells from the effector limb of the host immune response and could be used as a tool to facilitate allogeneic hepatocyte transplantation. (Hepatology 2007;45:755–766.)
Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy
Authors: Prasad Srinivasa , Dhiman Radha K. , Duseja Ajay , Chawla Yogesh K. , Sharma Arpita , Agarwal Ritesh 
Published: February 2007

Abstract

Minimal hepatic encephalopathy (MHE) has a negative effect on patients' daily functioning. Thus far, no study has investigated the effect of treatment-related improvement in cognitive functions on health-related quality of life (HRQOL). We measured psychometric performance by number and figure connection tests parts A and B, picture completion, and block design tests and HRQOL by the Sickness Impact Profile (SIP) of 90 patients with cirrhosis on inclusion into the study and 3 months later. A

Z

score less than −2 on the neuropsychological (NP) tests was considered abnormal. Sixty-one (67.7%) patients had MHE. They were randomly assigned in a 1:1 ratio to receive treatment (lactulose) for 3 months (n = 31) or no treatment (n = 30) in a nonblinded design. The mean number of abnormal NP tests decreased significantly in patients in the treated group (baseline, 2.74 [95% CI 2.40-3.08]; after 3 months, .75 [95% CI .36-1.16]) compared with patients in the untreated group (baseline, 2.47 [95% CI 2.19-2.74]; after 3 months, 2.55 [95% CI 2.16-2.94]); multivariate analysis of variance (MANOVA) for time and treatment,

P

= 0.001. The mean total SIP score improved among patients in the treated group (baseline, 10.39 [95% CI 9.36-11.43]; after 3 months, 3.77 [95% CI 2.52-5.02]) compared with patients in the untreated group (baseline, 10.36 [95% CI 8.98-11.73]; after 3 months, 10.39 [95% CI 8.36-12.42]); MANOVA for time and treatment,

P

= 0.002. Improvement in HRQOL was related to the improvement in psychometry.

Conclusion

: Treatment with lactulose improves both cognitive function and HRQOL in patients with cirrhosis who have MHE. (Hepatology 2007;45:549–559.)
Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection
Authors: Penna Amalia , Pilli Massimo , Zerbini Alessandro , Orlandini Alessandra , Mezzadri Sergio , Sacchelli Luca , Missale Gabriele , Ferrari Carlo 
Published: February 2007

Abstract

The functional impairment of HCV-specific T cell responses is believed to be an important determinant of HCV persistence, but the functional T cell defects of patients with chronic hepatitis C (CH-C) are only partially defined. CD8 responses to HLA-A2–restricted epitopes of HCV and other unrelated viruses were studied in 23 HLA-A2–positive patients both

ex vivo

and after

in vitro

culture. Degranulation capacity, intracellular perforin, and granzyme-A content and cytokine production (IFN-γ, TNF-α) by HCV- and non–HCV-specific CD8 cells were tested both

ex vivo

and

in vitro

, whereas cytolytic activity was studied after 10 days' expansion

in vitro

. Memory maturation and role of exhaustion were assessed

ex vivo

by HCV-specific CD8 staining for CD127 and PD-1, and

in vitro

after peripheral blood mononuclear cells (PBMC) culture in the presence of anti–PD-L1 monoclonal antibodies. IFN-γ production and cytolytic activity were expressed less efficiently by HCV-specific than by non–HCV specific CD8 cells derived from the same CH-C patients. The amount of stored granzyme-A within single cells was always lower in HCV-specific CD8 cells, which were less efficient also in the release of lytic granules and in the production of TNF-α. The CD8 dysfunction was associated with high PD-1 expression by most HCV-specific CD8 cells, and PD-1/PD-L1 blockade by anti–PD-L1 antibodies

in vitro

was able to improve the HCV-specific CD8 function.

Conclusion:

Our study characterizes CD8 defects that may be important in maintaining HCV persistence; identification of strategies to correct these defects may help to define novel approaches to treat HCV infection. (Hepatology 2007;45:588–601.)
TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window
Authors: Koschny Ronald , Ganten Tom M. , Sykora Jaromir , Haas Tobias L. , Sprick Martin R. , Kolb Armin , Stremmel Wolfgang , Walczak Henning 
Published: February 2007

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a novel promising anticancer biotherapeutic. However, TRAIL-resistant tumor cells require combinatorial regimens to sensitize tumor but not normal cells for TRAIL-induced apoptosis. Here, we investigated the mechanism of the synergistic antitumor effect of bortezomib in combination with TRAIL in hepatoma, colon, and pancreatic cancer cells in comparison to the toxicity in primary human hepatocytes (PHH). TRAIL cotreatment at high but clinically relevant concentrations of bortezomib caused toxicity in PHH which potentially limits the clinical applicability of bortezomib/TRAIL cotreatment. However, at low concentrations of bortezomib TRAIL-resistant hepatoma, colon and pancreatic cancer cell lines but not PHH were efficiently sensitized for TRAIL-induced apoptosis. RNA interference and TRAIL receptor blockage experiments revealed that in bortezomib-treated hepatoma cells TRAIL-R1/TRAIL-R2 up-regulation, enhanced TRAIL DISC formation and cFLIPL down-regulation in addition to accumulation of Bak cooperatively sensitized for TRAIL. Bim, although accumulated upon bortezomib treatment, did not play a causal role for TRAIL sensitization in Hep3b cells. Combined treatment with bortezomib and TRAIL massively reduced the clonogenic capacity of hepatoma cells

in vitro.

Surviving clones could be resensitized for repeated TRAIL treatment.

Conclusion:

Bortezomib/TRAIL cotreatment bears the risk of severe hepatotoxicity at high but clinically relevant concentrations of bortezomib. However, within a wide therapeutic window bortezomib sensitized different cancer cells but not PHH for TRAIL-induced apoptosis. (Hepatology 2007;45:649–658.)
Protection against Fas-induced liver apoptosis in transgenic mice expressing cyclooxygenase 2 in hepatocytes
Authors: Casado Marta , Mollá Belén , Roy Rosa , Fernández-Martínez Amalia , Cucarella Carme , Mayoral Rafael , Boscá Lisardo , Martín-Sanz Paloma 
Published: February 2007

Abstract

Cyclooxygenase-2 (COX-2) is upregulated in many cancers, and the prostanoids synthesized increase proliferation, improve angiogenesis, and inhibit apoptosis in several tissues. To explore the function of COX-2 in liver, transgenic (Tg) mice were generated containing a fusion gene (LIVhCOX-2) consisting of human COX-2 cDNA under the control of the human ApoE promoter. Six lines were developed; all of them expressed the LIVhCOX-2 transgene selectively in hepatocytes. The Tg mice exhibited a normal phenotype, and the increased levels of PGE2 found were due to the constitutively expressed COX-2. Histological analysis of different tissues and macroscopic examination of the liver showed no differences between wild-type (Wt) and Tg animals. However, Tg animals were resistant to Fas-mediated liver injury, as demonstrated by low levels of plasmatic aminotransferases, a lesser caspase-3 activation, and Bax levels and an increase in Bcl-2, Mcl-1, and xIAP proteins, when compared with the Wt animals. Moreover, the resistance to Fas-mediated apoptosis is suppressed in the presence of COX-2–selective inhibitors, which prevented prostaglandin accumulation in the liver of Tg mice.

Conclusion:

These results demonstrate that expression of COX-2–dependent prostaglandins exerted a protection against liver apoptosis. (Hepatology 2007;45:631–638.)
Identification of hepatocytic and bile ductular cell lineages and candidate stem cells in bipolar ductular reactions in cirrhotic human liver
Authors: Zhou Hongchao , Rogler Leslie E. , Teperman Lewis , Morgan Glyn , Rogler Charles E. 
Published: February 2007

Abstract

Hepatocyte function and regeneration are severely compromised in severe liver disease, and a common sequela is cirrhosis. Structural changes caused by cirrhosis create a cellular environment conducive to the formation of ductular reactions (DRs). Ductular reactions are primarily composed of oval cells also known as “intermediate hepatobiliary cells”. We have conducted single, double, and triple staining to study lineages of oval cells present in DRs. Staining with NCAM, CK19, and HepPar1 has revealed a distinctly bipolar structure to DRs that are embedded in cirrhotic tissue. Spatial analysis of cells that are singly HepPar1-positive, or CK19-positive, has revealed hepatocytic and biliary poles, respectively, in the DRs. Also, the location of singly NCAM-positive cells in DRs suggests that they may be bipotent liver stem/progenitor cells. The locations of other intermediate hepatobiliary cells, which have combinations of markers, suggest that CK19+/NCAM+ cells are transitional cells in the biliary lineage and that rare cells that are negative for all three markers are transitional cells in the hepatocytic lineage. A working cell lineage model for DRs is presented. (Hepatology 2007;45:716–724.)
Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma
Authors: Minuk Gerald Y. , Zhang Manna , Gong Yuewen , Minuk Leonard , Dienes Hans , Pettigrew Norman , Kew Michael , Lipschitz Jeremy , Sun Dongfeng 
Published: February 2007

Abstract

To determine whether hepatocyte membrane potential differences (PDs) are depolarized in human HCC and whether depolarization is associated with changes in GABAA receptor expression, hepatocyte PDs and γ-aminobutyric acid (GABA)A receptor messenger RNA (mRNA) and protein expression were documented in HCC tissues via microelectrode impalement, real-time reverse-transcriptase polymerase chain reaction, and Western blot analysis, respectively. HCC tissues were significantly depolarized (−19.8 ± 1.3 versus −25.9 ± 3.2 mV, respectively [

P

< 0.05]), and GABAA-β3 expression was down-regulated (GABAA-β3 mRNA and protein expression in HCC; 5,693 ± 1,385 and 0.29 ± 0.11 versus 11,046 ± 4,979 copies/100 mg RNA and 0.62 ± 0.16 optical density in adjacent tumor tissues, respectively [

P

= 0.002 and

P

< 0.0001, respectively]) when compared with adjacent nontumor tissues. To determine the physiological relevance of the down-regulation, human malignant hepatocytes deficient in GABAA-β3 receptor expression (Huh-7 cells) were transfected with GABAA-β3 complementary DNA (cDNA) or vector alone and injected into nu/nu nude mice (n = 16-17 group). Tumors developed after a mean (± SD) of 51 ± 6 days (range: 41-60 days) in 7/16 (44%) mice injected with vector-transfected cells and 70 ± 12 days (range: 59-86 days) in 4/17 (24%) mice injected with GABAA-β3 cDNA-transfected cells (

P

< 0.005).

Conclusion:

The results of this study indicate that (1) human HCC tissues are depolarized compared with adjacent nontumor tissues, (2) hepatic GABAA-β3 receptor expression is down-regulated in human HCC, and (3) restoration of GABAA-β3 receptor expression results in attenuated

in vivo

tumor growth in nude mice. (Hepatology 2007;45:735–745.)
Developing an alginate/chitosan hybrid fiber scaffold for annulus fibrosus cells
Authors: Shao Xinxin , Hunter Christopher J. 
Published: February 2007

AbstractA fibrous scaffold made of alginate or alginate/chitosan was fabricated for annulus fibrosus (AF) cell culture using a wet‐spinning and lyophilization technique. The scaffolds were evaluated using several in vitro tests. Scanning electron microscopy showed the scaffold fibers generally aligned in one direction with individual fiber diameters varying between 40–100 μm. The alginate/chitosan hybrid scaffold exhibited a slower degradation rate, while both scaffold types did not display any cyto‐toxicity to 3T3 fibroblasts and could maintain canine AF cell growth. The AF cells retained their spherical shape within the fibrous scaffold at the beginning of the culture period and formed into cell clusters at later times. Specific extracellular matrix molecules, including collagen I, collagen II, and aggrecan, could be detected in the AF cell clusters. These results demonstrate the feasibility of using this hybrid alginate/chitosan scaffold for AF cell culture, and the potential application for intervertebral disc tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Fibrin glue mixed with gelatin/hyaluronic acid/chondroitin‐6‐sulfate tri‐copolymer for articular cartilage tissue engineering: The results of real‐time polymerase chain reaction
Authors: Chou Cheng‐Hung , Cheng Winston T.K. , Kuo Tzong‐Fu , Sun Jui‐Sheng , Lin Feng‐Huei , Tsai Jui‐Che 
Published: February 2007

AbstractAutologous fibrin glue has been demonstrated as a potential scaffold with very good biocompatibility for neocartilage formation. However, fibrin glue has been reported not to provide enough mechanical strength, but with many growth factors to interfere the tissue growth. Gelatin/hyaluronic acid/chondroitin‐6‐sulfate (GHC6S) tri‐copolymer sponge has been prepared as scaffold for cartilage tissue engineering and showed very good results, but problems of cell seeding and cell distribution troubled the researchers. In this study, GHC6S particles would be added into the fibrin glue to provide better mechanical strength, better cell distribution, and easier cell seeding, which would be expected to improve cartilage regeneration in vitro. Porcine cryo‐precipitated fibrinogen and thrombin prepared from prothrombin activated by 10% CaCl2 solution were used in two groups. One is the fibrin glue group in which porcine chondrocytes were mixed with thrombin–fibrinogen solution, which was then converted into fibrin glue. The other is GHC6S‐fibrin glue in which GHC6S particles were added into the thrombin–fibrinogen solution with porcine chondrocytes. After culturing for 1–2 weeks, the chondrocytes cultured in GHC6S‐fibrin glue showed a round shape with distinct lacuna structure and showed positive in S‐100 protein immunohistochemical stain. The related gene expressions of tissue inhibitor of metalloproteinases‐1, matrix metalloproteinase‐2, MT1‐MMP, aggrecan, decorin, type I, II, X collagen, interleukin‐1 β, transforming growth factor‐β 1 (TGF‐β1), and Fas‐associating death domain were checked by real‐time PCR. The results indicated that the chondrocytes cultured in GHC6S‐fibrin glue would effectively promote extracellular matrix (ECM) secretion and inhibit ECM degradation. The evidence could support that GHC6S‐fibrin glue would be a promising scaffold for articular cartilage tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Synthesis of the anxiolytic agent [14C] 6‐hydroxy‐buspirone for use in a human ADME study
Authors: Bonacorsi Samuel J. , Burrell Richard C. , Luke George M. , DePue Jeffrey S. , Kent Rinehart J. , Balasubramanian Balu , Christopher Lisa J. , Iyer Ramaswamy A. 
Published: February 2007

AbstractA reliable synthesis of 14C labeled 6‐hydroxy‐buspirone is described. The molecule belongs to a unique class of compounds with the potential for anxiolytic activity. A radiolabeled analog was prepared to support the development of 6‐hydroxy‐buspirone. Specifically, a labeled variant was designed to meet the requirements of a human adsorption‐distribution‐metabolism‐elimination (ADME) study. Multiple 14C labels were needed to fully track the potential metabolic transformation of the molecule. Labeled 6‐hydroxy‐buspirone was prepared by oxidation of separately labeled versions of [14C]buspirone. The final product was isolated in reasonable yield with a radiochemical purity of 99.8%. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis of 18F‐labelled stilbenes from 4‐[18F]fluorobenz‐aldehyde using the Horner–Wadsworth–Emmons reaction
Authors: Gester Sven , Pietzsch Jens , Wuest Frank R. 
Published: February 2007

AbstractThe first application of the Horner–Wadsworth–Emmons reaction in 18F‐chemistry is described. This carbonyl‐olefination reaction was performed via a ‘multi‐step/one‐pot’ reaction by the coupling of benzylic phosphonic acid esters (3,5‐bis‐methoxymethoxybenzyl)‐phosphonic acid diethyl ester 2e, (4‐methoxy‐methoxybenzyl)‐phosphonic acid diethyl ester 3e and (4‐dimethyl‐aminobenzyl)phosphonic acid diethyl ester 4d) with 4‐[18F]fluorobenzaldehyde to give the corresponding 18F‐labelled stilbenes [18F]2g, [18F]3g and [18F]4e exclusively as the expected E‐isomers. The radiochemical yields ranged from 9% to 22% (based upon [18F]fluoride, including HPLC purification). The specific activity reached up to 90 GBq/µmol. Copyright © 2007 John Wiley & Sons, Ltd.
Reexamining the quantification of perfusion MRI data in the presence of bolus dispersion
Authors: Ko Linda , Salluzzi Marina , Frayne Richard , Smith Michael 
Published: February 2007

AbstractPurposeTo determine the true impact of dispersion upon cerebral blood flow (CBF) quantification by removing an algorithm implementation‐induced systematic error.Materials and MethodsThe impact of dispersion on the arterial input function (AIF) between measurement and entry into the tissue of interest on CBF estimates was simulated assuming: 1) contralateral circulation flow that introduces a true arterial tissue delay (ATD)‐related dispersive component; and 2) the presence of an arterial stenosis that disperses and shifts the AIF peak entering the tissue; increasing the apparent ATD relative to the original AIF.ResultsPreviously reported CBF estimates for the stenosis dispersion model were found to be a mixture of true dispersive effects and an algorithm implementation‐induced systematic error. The true CBFMEASURED/CBFNO‐DISPERSION ratios for short mean transit times (MTT) (normal) and long MTT (infarcted) tissue were similar for both dispersion models evaluated; this was an unanticipated result. The CBF quantification inaccuracies induced through the dispersion model truly related to ATD were lower than for the local stenosis‐based dispersion for small ATD values.ConclusionCorrecting the systematic error present in a previous deconvolution study removes the reported ATD‐related impact on CBF quantification. The impact of dispersion was smaller than half that reported in previous simulation studies. J. Magn. Reson. Imaging 2007;25:639–643. © 2007 Wiley‐Liss, Inc.
Breast carcinomas with strong high‐signal intensity on T2‐weighted MR images: Pathological characteristics and differential diagnosis
Authors: Yuen Sachiko , Uematsu Takayoshi , Kasami Masako , Tanaka Kumiko , Kimura Kiyomi , Sanuki Junichi , Uchida Yoshihiro , Furukawa Hiroyoshi 
Published: February 2007

AbstractPurposeTo investigate the histopathological characteristics of breast carcinomas with strong high‐signal intensity (SHi) on T2‐weighted (T2W) MR images (T2‐SHi), and discuss the differential diagnosis between T2‐SHi breast carcinomas and T2‐SHi fibroadenomas.Materials and MethodsThirty of 480 breast carcinomas examined by MRI were defined as tumors with T2‐SHi (defined as homogeneous higher signal intensity (SI) compared to surrounding normal breast tissue on fat‐suppressed T2W imaging (T2WI). They included eight mucinous and 22 nonmucinous carcinomas. The histopathological characteristics of T2‐SHi breast carcinomas, their signal‐to‐noise ratios (SNRs) on T2WI, contrast‐enhancement patterns, and morphology were compared with those of 22 non‐T2‐SHi breast carcinomas and 19 T2‐SHi fibroadenomas.ResultsIn nonmucinous carcinomas T2‐SHi was attributable to a mixture of background matrix, a higher proportion of cells than stroma, abundant cytoplasm, edematous stroma, and hemorrhage. The significantly high SNR (mean = 75) and enhancing internal septations seen in mucinous carcinomas, and the washout phenomenon, irregular border, absence of internal septation, and rim enhancement seen in nonmucinous carcinomas provide useful information for differentiating these tumors from T2‐SHi fibroadenomas.ConclusionA mixture of several histopathological characteristics was associated with T2‐SHi breast carcinomas. The combined information from T2WI and contrast‐enhanced (CE) imaging may help distinguish T2‐SHi breast carcinomas from T2‐SHi fibroadenomas. J. Magn. Reson. Imaging 2007;25:502–510. © 2007 Wiley‐Liss, Inc.