bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant non‐collagenous domain of α2(IV) collagen causes involution of choroidal neovascularization by inducing apoptosis
Authors: Lima e Silva Raquel , Kachi Shu , Akiyama Hideo , Shen JiKui , Aslam Sadia , Yuan Gong Yuan , Khu Naw Htee , Hatara Maria C. , Boutaud Ariel , Peterson Robert , Campochiaro Peter A.
Published: March 2006

Vascular endothelial cells receive proangiogenic or antiangiogenic signals from components of extracellular matrix (ECM) depending upon the situation and many molecular signals can have opposite effects in different vascular beds. Tissue inhibitor of metalloproteinase 1 is antiangiogenic in several tissues, but promotes retinal neovascularization. When cleaved from native collagens, several of the non‐collagenous domains (NC1) of basement membrane collagens have antiangiogenic effects in some tissues, but this is context dependent for the NC1 of the alpha 1 chain of collagen IV. It is critical to examine effects in several well‐defined model systems before assuming that an ECM component is universally antiangiogenic. In this study, we examined the effects of a recombinant fragment of NC1 of the alpha 2 chain of type IV collagen (α2(IV)NC1) in a well‐characterized model of ocular neovascularization. Intravitreous or periocular injections of α2(IV)NC1 caused selective apoptosis of endothelial cells participating in neovascularization resulting in suppression of neovascularization when the peptide was given prior to onset of new vessel sprouting. Importantly, when the peptide was given after neovascularization had already developed, it caused the new vessels to regress. This suggests that α2(IV)NC1, which has previously been shown to suppress tumor angiogenesis in xenograft models, is also a strong antiangiogenic agent in the choroid and is a therapeutic candidate for treatment of neovascular age‐related macular degeneration. © 2006 Wiley‐Liss, Inc.
Potentiation of TRPV3 channel function by unsaturated fatty acids
Authors: Hu Hong‐Zhen , Xiao Rui , Wang Chunbo , Gao Na , Colton Craig K. , Wood Jackie D. , Zhu Michael X.
Published: March 2006

Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31–39°C. We have previously shown that TRPV3 is activated by 2‐aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB‐induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA‐induced potentiation is observed in intracellular Ca2+ measurement, whole‐cell and two‐electrode voltage clamp studies, as well as single channel recordings of excised inside‐out and outside‐out patches. The fatty acid‐induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non‐metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Regulation of protein phosphatase 2A‐mediated recruitment of IQGAP1 to β1 integrin by EGF through activation of Ca2+/calmodulin‐dependent protein kinase II
Authors: Takahashi Kazuhide , Suzuki Katsuo
Published: March 2006

Maintenance of β1 integrin‐mediated cell adhesion in quiescent human mammary epithelial (HME) cells requires protein phosphatase (PP) 2A for not only dephosphorylation of β1 integrin but also recruitment of IQGAP1 to Rac‐bound β1 integrin. However, how PP2A‐dependent regulatory machinery of cell adhesion responds to EGF remains to be elucidated. We report here that phosphorylated Ca2+/calmodulin‐dependent protein kinase II (CaMKII) at threonine 286 was involved in the β1 integrin complex that consisted of PP2A, Rac, and IQGAP1 in quiescent HME cells. Stimulation of the cells with EGF concomitantly induced an increase in intracellular Ca2+, activation of CaMKII, and dissociation of PP2A‐IQGAP1‐CaMKII from β1 integrin‐Rac. Because the activation of CaMKII and dissociation of PP2A‐IQGAP1‐CaMKII were blocked by either Ca2+‐chelator or CaMKII inhibitor, we therefore propose that EGF has the ability to abrogate the PP2A function in the maintenance of β1 integrin‐mediated cell adhesion by dissociation of PP2A‐IQGAP1‐CaMKII from β1 integrin‐Rac through activation of CaMKII. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
A pilot study for nitrifying treatment of wastewater from fertilizer production using a gas–liquid–solid three‐phase flow airlift loop bioreactor
Authors: Wen Jianping , Liu Xianling , Yuan Qing , Zhao Xueming
Published: March 2006

An 80 m3 pilot‐scale gas–liquid–solid three‐phase flow airlift loop bioreactor (ALR) with a low ratio of height to diameter, in which a biological membrane replaced the activated sludge, was used in the nitrifying treatment of a real effluent from a fertilizer plant. The influences of pH value, air influx (Qg) and hydraulic residence time (HRT) on the reductions in chemical oxygen demand (COD) and ammonia nitrogen (NH4‐N) were investigated and are discussed herein. The optimum operating conditions were obtained at a pH value of 7.0–8.0, air influx of 500 m3 h−1 and an HRT of 10 h. Under these optimum conditions, the effluent COD and NH4‐N were less than 50 mg L−1 and 10 mg L−1 for a 40‐day run, which were far below the primary discharge standard for the chemical fertilizer industry in the People's Republic of China (COD ≤ 100 mg L−1 and NH4‐N ≤ 40 mg L−1). Furthermore, this pilot‐scale airlift loop bioreactor generated only one‐quarter of the sludge waste compared with the traditional activated sludge process. Copyright © 2006 Society of Chemical Industry
The extraction of rare earths using mixtures of acidic phosphorus‐based reagents or their thio‐analogues
Authors: Wang Xianglan , Li Wei , Meng Shulan , Li Deqian
Published: March 2006

The solvent extraction of rare earths from chloride solution has been investigated using mixtures of 2‐ethylhexylphosphonic acid mono‐(2‐ethylhexyl) ester (HEHEHP, P507) and organophosphorus acids [di‐(2‐ethylhexyl)phosphoric acid (HDEHP, P204), isopropylphosphonic acid 1‐hexyl‐4‐ethyloctyl ester (HHEOIPP), bis(2,4,4‐trimethylpentyl)phosphinic acid (Cyanex 272), bis(2,4,4‐trimethylpentyl)monothiophosphinic acid (Cyanex 302), and bis(2,4,4‐trimethypentyl)dithiophosphinic acid (Cyanex 301)]. Results show that the extractability of the selected extractants for rare earths decreases in the order: HEHEHP/HDEHP > HEHEHP/Cyanex 301 > HEHEHP/HHEOIPP > HEHEHP/Cyanex 302 > HEHEHP/Cyanex 272. A possible explanation of the different extractabilities is given based on the structure of the extractants. Furthermore, the possibilities of the separation of adjacent rare earths with these mixtures were investigated according to the extractabilities; the results show the possibility of separating the rare earths. Copyright © 2006 Society of Chemical Industry
Novel hydrogel composite for the removal of water‐soluble cationic dye
Authors: Zhang Li‐Ming , Zhou Yi‐Jun , Wang Yi
Published: March 2006

A novel hydrogel composite was prepared by incorporating Laponite RDS clay into poly(acrylic acid‐co‐N‐vinyl‐2‐pyrrolodone) hydrogel during in‐situ polymerization, and investigated with respect to its adsorption kinetics and isotherm toward Crystal Violet, a widely used cationic dye. It was found that the adsorption kinetics of Crystal Violet onto the hydrogel composite was consistent with the pseudo‐second‐order model. Compared with pure hydrogel, the hydrogel composite is characterized by greater amounts being adsorbed at equilibrium, and a higher rate constant and initial adsorption rate. By analyzing the experimental data using the Langmuir isotherm equation, an enhanced adsorption capacity was found for the hydrogel composite. Such material is expected to be a good adsorbent for water pollutants such as cationic dyes and treatment of these organic contaminants from wastewater. Copyright © 2006 Society of Chemical Industry
How many graphs are unions of k‐cliques?
Authors: Bollobás Béla , Brightwell Graham R.
Published: March 2006

We study the number $ F [n;k] $ of n‐vertex graphs that can be written as the edge‐union of k‐vertex cliques. We obtain reasonably tight estimates for $ F [n;k] $ in the cases (i) k = n − o(n) and (ii) k = o(n) but $ k/log\, n \to\infty $. We also show that $ F [n;k] $ exhibits a phase transition around $ k = log_2 n $. We leave open several potentially interesting cases, and raise some other questions of a similar nature. © 2006 Wiley Periodicals, Inc. J Graph Theory 52: 87–107, 2006
Explicit constructions of triple systems for Ramsey–Turán problems
Authors: Mubayi Dhruv , Sós Vera T.
Published: March 2006

We explicitly construct four infinite families of irreducible triple systems with Ramsey‐Turán density less than the Turán density. Two of our families generalize isolated examples of Sidorenko 14, and the first author and Rödl 12. Our constructions also yield two infinite families of irreducible triple systems whose Ramsey‐Turán densities are exactly determined. © 2006 Wiley Periodicals, Inc. J Graph Theory 52: 211–216, 2006
MRI of arthritis: Comparison of ultrasmall superparamagnetic iron oxide vs. Gd‐DTPA
Authors: Simon Gerhard H. , von Vopelius‐Feldt Johannes , Wendland Michael F. , Fu Yanjun , Piontek Guido , Schlegel Juergen , Chen Mei‐Hsiu , Daldrup‐Link Heike E.
Published: March 2006

Purpose

To compare the ability of the ultrasmall superparamagnetic iron oxide (USPIO) SHU555C vs. gadopentetate dimeglumine (Gd‐DTPA) to detect antigen‐induced monoarthritis with MRI.

Materials and Methods

Twelve seven‐week‐old female rats with an antigen‐induced monoarthritis of the right knee were randomly assigned to two groups. Animals in group I (N = 6) underwent MRI using T1‐weighted gradient‐echo sequences before injection and at 2, 9, 17, 25, 33, 40, 47, 55, and 63 minutes postinjection (p.i.) of Gd‐DTPA on day 1, and before injection and at 3, 23, 43, and 123 minutes p.i. of SHU555C on day 2. Animals in group II (N = 6) were imaged before injection and at 3, 23, 43, and 123 minutes p.i. using identical sequences. Signal‐to‐noise ratios (SNRs) and relative enhancement (ΔSI%) of arthritic and normal synovium were determined from region‐of‐interest (ROI) measurements in consensus reading by two experienced radiologists. Data were tested for significant differences between the two agents and between the arthritic and normal knees using a mixed‐effect model and F‐tests (P < 0.05). Joints were processed for histopathology as the gold standard.

Results

USPIO and Gd‐DTPA showed significant enhancement differences (P < 0.001). USPIO provided a progressive and persistent enhancement of arthritic joints while Gd‐DTPA provided an early and rapidly declining enhancement. Maximal enhancement in synovitis was 400% at 40–120 minutes p.i. of USPIO vs. 300% at two minutes p.i. of Gd‐DTPA. USPIO provided a significant higher difference in enhancement between the arthritic and normal synovium than Gd‐DTPA (P < 0.001). Histopathology confirmed marked inflammatory synovial changes in all arthritis‐induced right knee joints and normal synovium in all left knee joints.

Conclusion

Both USPIO and Gd‐DTPA detect arthritis by positive T1‐enhancement. Compared to standard Gd‐DTPA, the USPIO SHU555C provides a comparable maximal T1‐enhancement (at two minutes p.i for Gd‐DTPA and between 43 and 123 minutes p.i. for SHU555C), but in addition it provides a prolonged T1‐enhancement of synovitis and a higher difference between the relative enhancement of arthritic and normal synovium. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Free‐breathing whole‐heart coronary MR angiography on a clinical scanner in four minutes
Authors: Nehrke Kay , Börnert Peter , Mazurkewitz Peter , Winkelmann Richard , Gräßlin Ingmar
Published: March 2006

Purpose

To set up a robust and patient‐friendly whole‐heart protocol based on 32‐receive‐channel technology that will potentially allow a large part of the patient population to be addressed.

Materials and Methods

Ten volunteers were examined on a clinical 1.5 T scanner equipped with a 32‐channel data acquisition system using an experimental 32‐element coil array. A magnetization‐prepared, navigator‐gated and ‐tracked 3D Cartesian balanced FFE sequence was used for whole‐heart coronary MR angiography (MRA). With the use of sensitivity encoding (SENSE) and partial Fourier encoding for scan acceleration, nearly isotropic high‐resolution data sets were acquired during free breathing in four minutes.

Results

A high contrast and sufficient signal‐to‐noise ratio (SNR) were obtained, which allowed visualization of the major vessels up to the distal regions and detection of major branches. Phase encoding in the anterior–posterior (AP) direction was the most favorable SENSE configuration and allowed a reasonable scan time reduction with moderate SENSE factors.

Conclusion

The employed 32‐receive channel technology enabled a robust trade‐off among SNR, spatial resolution, and scan time. In this study the most robust results were obtained using the smallest possible SENSE factors for a given voxel size and scan time. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival
Authors: Xu Xiao , Man Kwan , Zheng Shu Sen , Liang Ting Bo , Lee Terence K. , Ng Kevin T. , Fan Sheung Tat , Lo Chung Mau
Published: March 2006

The major concern of living donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be developed. To investigate the protective effect of somatostatin related to hemodynamic stress on small-for-size liver graft injury, we applied a treatment regimen of low-dose somatostatin in a rat orthotopic liver transplantation model using small-for-size grafts (median, 38.7%; range, 35–42%). Somatostatin was given at 5 minutes before total hepatectomy and immediately after reperfusion in the recipient (20 μg/kg). Graft survival, portal hemodynamics, intragraft gene expression and hepatic ultrastructural changes were compared between the rats with or without somatostatin treatment. Seven-day graft survival rates in the somatostatin treatment group were significantly improved compared to the control group (66.7% vs. 16.7%, P = 0.036). In the treatment group, portal pressure and hepatic surface blood flow were significantly decreased within the first 30 minutes after reperfusion, whereas in the control group, transient portal hypertension and excessive hepatic blood flow were observed. Intragraft expression (both messenger RNA and protein) of endothelin-1 was significantly downregulated accompanied with upregulation of heme oxygenase-1 and A20. Better preservation of liver function was found in the treatment group. Hepatic ultrastructure, especially the integrity of sinusoids, was well protected in the treatment group. In conclusion, low-dose somatostatin rescues small-for-size grafts from acute phase injury in liver transplantation by attenuation of acute-phase shear stress that resulted from transient portal hypertension.
Liver Transpl 12:621–627, 2006.

© 2006 AASLD.
Minimizing oxidative stress by gene delivery of superoxide dismutase accelerates regeneration after transplantation of reduced-size livers in the rat
Authors: Lehmann Thorsten G. , Luedde Tom , Schwabe Robert F. , Bunzendahl Hartwig , Samulski Jude R. , Lemasters John J. , Brenner David A.
Published: March 2006

Transplantation of reduced-size livers may lead to a hypermetabolic state and increased production of oxygen radicals. Since oxygen radicals may cause liver injury and impair liver regeneration, we tested the hypothesis that overexpression of superoxide dismutase (SOD) in reduced-size livers (RSL) would accelerate regeneration and reduce injury in a rat model of transplantation of RSL. Donor rats were infected with adenoviruses either expressing SOD1 (Ad.SOD1) or beta-galactosidase (Ad.lacZ). Livers were harvested 72 hours later, reduced to 45% of weight, and transplanted. After transplantation, hepatic SOD activity, graft survival, histopathology, AST/ALT release, and bilirubin were examined. Regeneration was evaluated by BrdU-staining, graft weight, and expression of cyclin D1 and p21. In Ad.SOD1-treated livergrafts, SOD activity increased three-fold compared to controls. Survival was dramatically increased in recipients of Ad.SOD1-RSL (100% vs. 20% in Ad.lacZ-RSL), and peak levels of AST/ALT and bilirubin levels were reduced by 75% and 87.5%, respectively (P < 0.001). In histological sections, hepatocyte necrosis decreased from 24% after Ad.lacZ–treatment to 6% after Ad.SOD1-treatment (P <0.001). Regeneration was also accelerated after Ad.SOD1-treatment as demonstrated by an increase of BrdU-stained cells 24 hours after reperfusion and increased liver weight after 1 week. In conclusion, overexpression of SOD1 in RSL prevents primary non-function of reduced-size liver grafts and accelerates liver regeneration.
Liver Transpl 12:550–559, 2006.

© 2006 AASLD.
Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction
Authors: Cordoba Shaun P. , Wang Chuanmin , Williams Rohan , Li Jian , Smit Lynn , Sharland Alexandra , Allen Richard , McCaughan Geoffrey , Bishop Alex
Published: March 2006

This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta-analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty-six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT-1, IRF-1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT-PCR. The results were compared to two published high-throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT-1 and IRF-1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT-1, IRF-1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT-1/IRF-1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism.
Liver Transpl 12:636–643, 2006.

© 2006 AASLD.
Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study
Authors: Cescon Matteo , Grazi Gian Luca , Grassi Alberto , Ravaioli Matteo , Vetrone Gaetano , Ercolani Giorgio , Varotti Giovanni , D'Errico Antonietta , Ballardini Giorgio , Pinna Antonio Daniele
Published: March 2006

The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC− group, n = 24) IPC (10-min ischemia + 15-min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC− group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC− group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC− group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC− group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC−, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits.
Liver Transpl 12:628–635, 2006.

© 2006 AASLD.
Influence of donor/recipient HLA-matching on outcome and recurrence of hepatitis C after liver transplantation
Authors: Langrehr Jan Michael , Puhl Gero , Bahra Marcus , Schmeding Maximilian , Spinelli Antonino , Berg Thomas , Schönemann Constanze , Krenn Veit , Neuhaus Peter , Neumann Ulf Peter
Published: March 2006

The aim of this study was to analyze the effect of human leukocyte antigen (HLA) matching on outcome, severity of recurrent hepatitis C and risk of rejection in hepatitis C positive patients after liver transplantation (LT). In a retrospective analysis, 165 liver transplants in patients positive for hepatitis C virus (HCV) with complete donor/recipient HLA typing were reviewed for recurrence of HCV and outcome. Follow-up ranged from 1 to 158 months (median, 74.5 months). Immunosuppression consisted of either cyclosporine-A- or tacrolimus-based quadruple induction therapy including or an interleukin 2-receptor antagonist. Protocol liver biopsies were performed after 1, 3, 5, 7, and 10 years and staged according to the Scheuer scoring system. The overall 1-, 5-, and 10-year graft survival figures were 81.8%, 69.11 and 62%, respectively. There was no correlation in the study population between number of HLA mismatches and graft survival. The number of rejection episodes increased significantly in patients with more HLA mismatches (P < 0.05). In contrast to this, the fibrosis progression was significantly faster in patients with 0–5 HLA mismatches compared to patients with a complete HLA mismatch. In conclusion, HLA matching did not influence graft survival in patients after LT for end-stage HCV infection, however, despite less rejection episodes, the fibrosis progression increased in patients with less HLA mismatches within the first year after LT.
Liver Transpl 12:644–651, 2006.

© 2006 AASLD.
Value of dobutamine stress myocardial contrast perfusion echocardiography in patients with advanced liver disease
Authors: Tsutsui Jeane M. , Mukherjee Sandeep , Elhendy Abdou , Xie Feng , Lyden Elizabeth R. , O'Leary Edward , McGrain Anna C. , Porter Thomas R.
Published: March 2006

Although dobutamine stress echocardiography has been used for the preoperative evaluation of patients with advanced liver disease (ALD), no data exist regarding the value of myocardial perfusion imaging (MPI) with real-time myocardial contrast echocardiography (RTMCE) in this patient population. We sought to determine the value of MPI during dobutamine stress RTMCE for predicting prognosis in patients with ALD. We examined both wall motion and MPI in 230 patients with ALD who underwent dobutamine stress RTMCE using intravenous commercially available contrast agents (Optison, GE-Amersham, Princeton, NJ; or Definity, Bristol-Myers Squibb Medical Imaging, North Billerica, MA). The prognostic value of clinical variables, including the Model for End-Stage Liver Disease (MELD) score, and echocardiographic data were examined using a Cox Hazard model. The primary endpoint was mortality of all causes. Among the 85 patients who underwent orthotopic liver transplantation, 4 had abnormal MPI and 81 had normal perfusion. The hospital mortality rate was 50% (2/4) in patients with abnormal MPI and 2% (2/81) in patients with normal MPI (P = 0.01). Among patients with abnormal MPI, 1 died from myocardial infarction in the first postoperative day and the second 1 from hemorrhagic shock. During a median follow-up of 15 months, 53 (23%) patients died. The independent predictors of death were an age of ≥65 yr (RR = 2.2; 95% confidence interval (CI) = 1.1–4.4; P = 0.03), MELD score of ≥25 (RR = 3.2; 95% CI = 1.8–5.5; P < 0.0001), and abnormal MPI (RR = 2.4; 95% CI = 1.1–5.2; P = 0.02). The 2-yr mortality was 24% for patients with normal MPI and 45% for those with inducible MPI abnormalities (P = 0.003). In conclusion, MPI obtained by RTMCE appears to be a useful tool in predicting mortality in patients with ALD. Further studies are required to verify its independent value.
Liver Transpl 12:592–599, 2006.

© 2006 AASLD.
Late graft dysfunction and autoantibodies after liver transplantation in children: Preliminary results of an italian experience
Authors: Riva Silvia , Sonzogni Aurelio , Bravi Michela , Bertani Alessandro , Alessio Maria Grazia , Candusso Manila , Stroppa Paola , Melzi Maria L. , Spada Marco , Gridelli Bruno , Colledan Michele , Torre Giuliano
Published: March 2006

Late graft dysfunction (GD) associated with the development of autoantibodies is a common event after pediatric liver transplantation (OLTx) and can present in 2 clinicohistological subsets: de novo autoimmune hepatitis (DNAH) and early chronic rejection (ECR). Sixty out of 247 children developed autoantibodies after OLTx. GD was demonstrated in 22 (37%); based on histology, patients were divided in a DNAH and an ECR group. Portal/periportal inflammatory infiltrate with interface/lobular hepatitis was suggestive for DNAH. Pericentral hepatocytes confluent dropout with a variable degree of central vein endothelitis, but not with ductopenia (loss of >50% of interlobular bile ducts), was diagnosed as ECR. Nine patients had DNAH and 13 ECR. Five out of 9 in the DNAH group were on cyclosporin (CsA) and 4/9 were on tacrolimus (Tac). In the ECR group, 11 children were treated with CsA and 2 with Tac. All DNAH patients had normal liver function tests on steroids and azathioprine (AZA). Five patients with ECR recovered by increasing calcineurin inhibitors (CNIs) dosage, but in 8/13, including 7 switched from CsA to Tac, AZA and steroids were added to obtain remission of disease. Two patients developed late chronic rejection. DNAH and ECR associated with autoantibodies are forms of late GD after OLTx. DNAH improves after standard treatment of autoimmune hepatitis. ECR has a good response to increased doses of CNIs, although ductopenic chronic rejection may occur. In conclusion, the early differential diagnosis of these conditions and an appropriate treatment seem to allow good overall results reflected by a graft survival of more than 90%.
Liver Transpl 12:573–577, 2006.

© 2006 AASLD.
The association of HLA-DR13 with lower graft survival rates in hepatitis B and primary sclerosing cholangitis caucasian patients receiving a liver transplant
Authors: Futagawa Yasuro , Waki Kayo , Cai Junchao
Published: March 2006

We investigated an association of human leukocyte antigen (HLA)-DR13 to graft survival in liver transplantation among Caucasian recipients. 28,708 deceased liver transplants performed between January 1990 and December 2002 in the United States as reported to the United Network for Organ Sharing registry were utilized to compare survival rates. We utilized Caucasian adult patients (>20 years) by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard analyses. HLA-DR13-negative hepatitis B virus (HBV) and primary sclerosing cholangitis (PSC) recipients yielded significantly lower graft survival rates than those of DR13-negative patients (P = 0.002, P = 0.015, respectively). This negative association was still significant after adjusting potential confounding factors. The Cox test demonstrated that HLA-DR13-positive groups have a significantly higher hazard ratio in PSC (1.40; P = 0.029; 95% confidence interval, 1.04–1.90) and HBV patients (1.78; P = 0.032; 95% confidence interval, 1.05–3.02). In conclusion, our data suggest that HLA-DR13 is a strong, positive predictor of increased risk for graft loss in HBV and PSC liver transplant recipients. Further study is needed to test the hypothesis that DR13-related immune responses may play a role in mediating graft loss in HBV and PSC liver transplantations.
Liver Transpl 12:600–604, 2006.

© 2006 AASLD.
The effect of HLA class I (A and B) and class II (DR) compatibility on liver transplantation outcomes: An analysis of the OPTN database
Authors: Navarro Victor , Herrine Steven , Katopes Charles , Colombe Beth , Spain Victor C.
Published: March 2006

The purpose of this study was to explore the relationship between human leukocyte antigen (HLA) compatibility and liver transplantation outcomes by analyzing the effect of HLA compatibility on 5-year graft survival. We analyzed first liver transplants between 1987 and 2002 in the Organ Procurement and Transplantation Network (OPTN) database, where A, B, or DR loci data were available. Graft failure was defined as retransplantation or death from transplant-related cause. We evaluated associations between total and locus-specific match levels and 5-year graft survival. Multivariable Cox proportional-hazard models were used to evaluate statistical interactions and adjust for the effect of potential confounders. Among 29,675 first-time transplants, the overall degree of HLA match had no effect on 5-year graft survival, even after controlling for potential confounders. Univariate and multivariable analyses showed that the 0 HLA antigen mismatch cohort of patients had higher 5-year graft failure rates than the other 6 antigen mismatch groups. However, this occurred in a small group with a disproportionately large number of live donors and split-liver recipients. When these recipients were excluded from the analysis, the effect was no longer seen. Finally, multivariable, locus-specific analyses showed no association between 5-year graft survival and degree of match/mismatch and the A, B, or DR loci. In conclusion, this careful examination of the OPTN database, with respect to HLA match or mismatch and liver graft survival, reaffirms that HLA matching has no clinically significant impact on this outcome.
Liver Transpl 12:652–658, 2006.

© 2006 AASLD.
KICG value, a reliable real-time estimator of graft function, accurately predicts outcomes in adult living-donor liver transplantation
Authors: Hori Tomohide , Iida Taku , Yagi Shintaro , Taniguchi Kentaro , Yamamoto Chiduru , Mizuno Shugo , Yamagiwa Kentaro , Isaji Shuji , Uemoto Shinji
Published: March 2006

Reliable monitoring enabling evaluation of graft function is crucial after living-donor liver transplantation (LDLT). A method to identify poor graft function at an early postoperative period would allow opportune intensive clinical management to bring about further improvements in LDLT outcomes. This study assessed the reliability of the indocyanine green (ICG) elimination rate constant (KICG) value as an estimator of graft function and determined the actual temporal changes of KICG after LDLT. KICG values were measured using a noninvasive method in 30 adult recipients up to 28 days after LDLT. The receptor index (LHL15) based on liver scintigraphy, and graft parenchymal damage score based on histopathological findings were evaluated after LDLT and correlated well with simultaneous KICG. Thus, KICG measured by noninvasive method was confirmed as accurately evaluating graft function. Changes of KICG after LDLT in recipients with good graft function were maintained, after some falls in the early periods, and had a significant difference compared with those for recipients without good graft function; moreover, there were already significant differences in KICG 24 hours after LDLT. Mean transit time reflecting systemic hemodynamics revealed that recipients without good outcomes fell into an unstable systemic hemodynamic state, and effective hepatic blood flow has a large influence on liver regeneration after LDLT. In conclusion, we suggested that KICG values can predict clinical outcomes at the early postoperative period after LDLT by sharply reflecting the influence of systemic dynamics on splanchnic circulation.
Liver Transpl 12:605–613, 2006.

© 2006 AASLD.
Role of integrins, tetraspanins, and ADAM proteins during the development of apoptotic bodies by spermatogenic cells
Authors: Kierszenbaum Abraham L. , Rosselot Carolina , Rivkin Eugene , Tres Laura L.
Published: March 2006

We have previously reported that Sertoli cell geometric changes induced by a Fas (CD95) agonist or by restricting Sertoli cell spreading can trigger spermatogenic cell detachment from Sertoli cell surfaces and initiate a programmed cell death sequence. Here, we have focused on ADAM proteins, tetraspanins CD9 and CD81, and the integrin β1 subunit, which is co‐expressed in testis with integrin α3 and integrin α6 subunits, to understand how these molecules may stabilize spermatogenic cell attachment to Sertoli cell surfaces. Like ADAM proteins, integrin β1, α3, and α6 subunits, and CD9 and CD81 transcripts are expressed in the fetal testis and throughout testicular maturation, as well as, in Sertoli‐spermatogenic cell co‐ cultures. Prespermatogonia (gonocytes) display CD9 and CD81 immunoreactive sites. Integrin α6 subunit transcripts have unusual developmental characteristics: fetal testis expresses the integrin α6B isoform exclusively. In contrast, the integrin α6B isoform co‐exists with the integrin α6A isoform in prepubertal testes and Sertoli‐spermatogenic cell co‐cultures. A blocking anti body targeting the extracellular domain (N‐terminal) of the integrin β1 subunit causes rapid contraction of Sertoli cells leading to the gradual detachment of associated spermatogenic cells. In contrast, predicted active site peptides targeting the disintegrin domain of ADAM 1, ADAM 2, ADAM 3 (cyritestin), ADAM 4, ADAM 5, ADAM 6, and ADAM 15 (metragidin) do not disturb significantly the attachment of spermatogenic cells to Sertoli cell surfaces. Spermatogenic cells dislodged from their attachment sites by the integrin β1 subunit blocking antibody display annexin V immunoreactivity, a sign of early apoptosis. Time‐lapse videomicroscopy demonstrates that the removal by apoptosis of a single member of a spermatogenic cell cohort inter‐connected by cytoplasmic bridges does not affect the remaining members of the cohort. During spermatogenic cell apoptosis, integrin β1, α3, and α6 subunits, and tetraspanins CD9 and C81 become displaced away from the developing apoptotic bodies. In contrast, the intermediate filament protein Sak57, a keratin 5 ortholog, concentrates in the developing apoptotic bodies. We propose that the redistribution of integrin–tetraspanin complexes during spermatogenic cell apoptosis may be evidence of a signaling cascade initiated by Sertoli cell geometric changes. As a result, Sertoli cell reduction in surface area may be a limiting factor of spermatogenic cell survival and in the developmental regulation of spermatogenic cell progenies in the intact seminiferous epithelium. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
The influence of the construction process on the deformation behaviour of diaphragm walls in soft clayey ground
Authors: Schäfer R. , Triantafyllidis Th.
Published: March 2006

Conventional numerical predictions of deep excavations normally neglect the construction process of the retaining structure and choose the earth pressure at rest as initial condition at the beginning of the simulation. The presented results of simulation and measurements during the construction process of the Taipei National Enterprise Center show, that such an assumption leads to an underestimation of the horizontal wall deflection, the surface ground settlements as well as the loading of the struts in case of normally to slightly over‐consolidated clayey soil deposits. The stepwise installation process of the individual diaphragm wall panels results in a substantial modification of the lateral effective stresses in the adjacent ground. Especially the pouring process of the panel and the fresh concrete pressure causes a partial mobilization of the passive earth pressure and a distinct stress level increase in the upper half of the wall. As a consequence of the increased stresses prior to the pit excavation, up to 15% greater ground and wall movements are predicted. Moreover, the increased stress level due to the installation process of the diaphragm wall leads to substantial higher strut loadings during the excavation of the pit. Copyright © 2006 John Wiley & Sons, Ltd.
A variable time transformation method for mixed‐integer optimal control problems
Authors: Gerdts Matthias
Published: March 2006

The article discusses a variable time transformation method for the approximate solution of mixed‐integer non‐linear optimal control problems (MIOCP). Such optimal control problems enclose real‐valued and discrete‐valued controls. The method transforms MIOCP using a discretization into an optimal control problem with only real‐valued controls. The latter can be solved efficiently by direct shooting methods. Numerical results are obtained for a problem from automobile test‐driving that involves a discrete‐valued control for the gear shift of the car. The results are compared to those obtained by Branch&Bound and show a drastic reduction of computation time. This very good performance makes the suggested method applicable even for many discretization points. Copyright © 2006 John Wiley & Sons, Ltd.
Is proton cationization promoted by polyatomic primary ion bombardment during time‐of‐flight secondary ion mass spectrometry analysis of frozen aqueous solutions?
Authors: Conlan Xavier A. , Lockyer Nicholas P. , Vickerman John C.
Published: March 2006

Ion bombardment of pure water ice by Au+ monoatomic and Au and C polyatomic projectiles results in the emission of two series of water cluster ions—(H2O) and (H2O)nH+—with n ranging from 1 to >40. The cluster ion yields are very significantly higher under polyatomic ion bombardment than when using an Au+ primary ion. The yield of the protonated water species (H2O)nH+ is found to be enhanced by increasing ion fluence. C bombardment results in a very dramatic increase in the (H2O)nH+ yield and decrease in the yield of (H2O). Au also significantly increased the yield of protonated species relative to the non‐protonated but to a lesser extent than C. Bombardment by Au+ also increased the yield of protonated species but to a very much smaller extent. The hypothesis that the protonated species may enhance the yield of [M+H]+ from solute molecules in solution has been investigated using two amino acids, alanine and arginine, and a nucleic base, adenine. The data suggest that the protons produced by the sputtering of water ice are depleted in the presence of these solutes and concurrently the yields of solute‐related [M+H]+ and immonium secondary ions are greatly enhanced. These yield enhancements are analysed in the light of other possible contributors such as increased rates of sputtering under polyatomic beams and increased secondary ion yields as a consequence of solute dispersion. It is concluded that enhanced proton attachment is occurring in polyatomic sputtered frozen aqueous solutions. Copyright © 2006 John Wiley & Sons, Ltd.
Chemometric evaluation of time‐of‐flight secondary ion mass spectrometry data of minerals in the frame of future in situ analyses of cometary material by COSIMA onboard ROSETTA
Authors: Engrand Cecile , Kissel Jochen , Krueger Franz R. , Martin Philippe , Silén Johan , Thirkell Laurent , Thomas Roger , Varmuza Kurt
Published: March 2006

Chemometric data evaluation methods for time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) have been tested for the characterization and classification of minerals. Potential applications of these methods include the expected data from cometary material to be measured by the COSIMA instrument onboard the ESA mission ROSETTA in the year 2014. Samples of the minerals serpentine, enstatite, olivine, and talc have been used as proxies for minerals existing in extraterrestrial matter. High mass resolution TOF‐SIMS data allow the selection of peaks from inorganic ions relevant for minerals. Multivariate cluster analysis of peak intensity data by principal components analysis and the new method CORICO showed a good separation of the mineral classes. Classification by k nearest‐neighbor classification (KNN) or binary decision trees (CART method) results in more than 90% correct class assignments in a leave‐one‐out cross validation. Copyright © 2006 John Wiley & Sons, Ltd.
Improvement of 2,4‐dinitrophenylhydrazine derivatization method for carbon isotope analysis of atmospheric acetone
Authors: Wen Sheng , Yu Yingxin , Guo Songjun , Feng Yanli , Sheng Guoying , Wang Xinming , Bi Xinhui , Fu Jiamo , Jia Wanglu
Published: March 2006

Through simulation experiments of atmospheric sampling, a method via 2,4‐dinitrophenylhydrazine (DNPH) derivatization was developed to measure the carbon isotopic composition of atmospheric acetone. Using acetone and a DNPH reagent of known carbon isotopic compositions, the simulation experiments were performed to show that no carbon isotope fractionation occurred during the processes: the differences between the predicted and measured data of acetone‐DNPH derivatives were all less than 0.5‰. The results permitted the calculation of the carbon isotopic compositions of atmospheric acetone using a mass balance equation. In this method, the atmospheric acetone was collected by a DNPH‐coated silica cartridge, washed out as acetone‐DNPH derivatives, and then analyzed by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Using this method, the first available δ13C data of atmospheric acetone are presented. Copyright © 2006 John Wiley & Sons, Ltd.
Water extraction times for plant and soil materials used in stable isotope analysis
Authors: West Adam G. , Patrickson Shela J. , Ehleringer James R.
Published: March 2006

Stable isotopic analysis of water for many ecological applications commonly requires extractions of water from dozens to hundreds of plant and soil samples. With recent advances in mass spectrometry, water extraction, rather than the isotopic analysis itself, is the bottleneck in sample processing. Using cryogenic vacuum distillation, we have created extraction timing curves to determine how much time (Tmin) is required to extract an unfractionated water sample. Our results indicated that Tmin values are 60 to 75 min for stems, 40 min for clay soils, 30 min for sandy soils and 20 to 30 min for leaves. While the extraction times reported here may allow for some reductions relative to times reported in the literature, the extraction process will continue to be a rate‐limiting step in plant water analyses. Ultimately, technological advances eliminating the need for extraction are required to greatly increase throughput rates in water isotope analysis for ecological research. Copyright © 2006 John Wiley & Sons, Ltd.
Quantification of benzo[a]pyrene diol epoxide DNA‐adducts by stable isotope dilution liquid chromatography/tandem mass spectrometry
Authors: Ruan Qian , Kim Hye‐Young H. , Jiang Hao , Penning Trevor M. , Harvey Ronald G. , Blair Ian A.
Published: March 2006

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants found in car exhausts, charbroiled food, and tobacco smoke. Three pathways for the metabolic activation of B[a]P to ultimate carcinogens have been proposed. The most widely accepted pathway involves cytochrome‐P450 (CYP) 1A1‐ and/or 1B1‐mediated formation of B[a]P‐7,8‐oxide, which undergoes epoxide hydrolase‐mediated metabolism to the proximate carcinogen B[a]P‐7,8‐dihydro‐7,8‐diol. Further CYP1A1‐ and/or CYP1B1‐mediated activation of the dihydrodiol results in the formation of 7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene (B[a]PDE), the ultimate carcinogen. In previous studies, it was demonstrated that (+)‐anti‐B[a]PDE was the most potent tumorigen of the CYP‐derived B[a]PDE diastereomers. We have developed a stable isotope dilution, liquid chromatography multiple reaction monitoring/mass spectrometry (LC‐MRM/MS) assay for all eight (±)‐anti‐B[a]PDE‐derived dGuo and dAdo DNA‐adducts. The LC‐MRM/MS assay was rigorously validated and used to show that (+)‐anti‐trans‐B[a]PDE‐dGuo was the major adduct formed when naked DNA and human bronchoalveolar adenocarcinoma H358 cells were treated with (±)‐anti‐B[a]PDE. The preference for DNA‐adducts derived from (+)‐anti‐B[a]PDE was even more apparent in cellular DNA. Thus, the increased potency of (+)‐anti‐B[a]PDE as a tumorigen is most likely due its ability to preferentially form DNA‐adducts when compared with (−)‐anti‐B[a]PDE. Also, the adduct profile suggests that this occurs by binding of (+)‐anti‐B[a]PDE to DNA in a manner that facilitates covalent binding to dGuo rather than dAdo residues. Copyright © 2006 John Wiley & Sons, Ltd.
Ultra‐performance liquid chromatography coupled to linear ion trap mass spectrometry for the identification of drug metabolites in biological samples
Authors: Dear G. J. , James A. D. , Sarda S.
Published: March 2006

The coupling of ultra‐performance liquid chromatography, operating at elevated pressures, to a linear ion trap mass spectrometer provides a high‐performance system suitable for drug metabolite characterisation. This system demonstrates improved chromatographic efficiency and sensitivity and at the same time provides diagnostic MSndata often critical for metabolite structural assignment. The linear ion trap was capable of dealing with the high chromatographic efficiencies and hence narrow peak widths associated with 1.7 µm particle‐packed column separations. Polarity switching and data‐dependent MSndata were generated with ease, and applied to the identification of metabolites found in human plasma. Copyright © 2006 John Wiley & Sons, Ltd.
Expert models and modeling processes associated with a computer‐modeling tool
Authors: Zhang BaoHui , Liu Xiufeng , Krajcik Joseph S.
Published: March 2006

Holding the premise that the development of expertise is a continuous process, this study concerns expert models and modeling processes associated with a modeling tool called Model‐It. Five advanced Ph.D. students in environmental engineering and public health used Model‐It to create and test models of water quality. Using “think aloud” technique and video recording, we captured their computer screen modeling activities and thinking processes. We also interviewed them the day following their modeling sessions to further probe the rationale of their modeling practices. We analyzed both the audio–video transcripts and the experts' models. We found the experts' modeling processes followed the linear sequence built in the modeling program with few instances of moving back and forth. They specified their goals up front and spent a long time thinking through an entire model before acting. They specified relationships with accurate and convincing evidence. Factors (i.e., variables) in expert models were clustered, and represented by specialized technical terms. Based on the above findings, we made suggestions for improving model‐based science teaching and learning using Model‐It. © 2006 Wiley Periodicals, Inc. Sci Ed 90:579–2604, 2006