bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABC-transporters are localized in caveolin-1-positive and reggie-1-negative and reggie-2-negative microdomains of the canalicular membrane in rat hepatocytes #
Authors: Ismair Manfred G. , Häusler Stephanie , Stuermer Claudia A. , Guyot Christelle , Meier Peter J. , Roth Jürgen , Stieger Bruno 
Published: December 2008

Abstract
The canalicular plasma membrane is constantly exposed to bile acids acting as detergents. Bile acids are essential to mediate release of biliary lipids from the canalicular membrane. Membrane microdomains (previously called lipid rafts) are biochemically defined by their resistance to detergent solubilization at cold temperature. We aimed to investigate the canalicular plasma membrane for the presence of microdomains, which could protect this membrane against the detergent action of bile acids. Highly purified rat liver canalicular plasma membrane vesicles were extracted with 1% Triton X-100 or 1% Lubrol WX at 4°C and subjected to flotation through sucrose step gradients. Both detergents yielded detergent-resistant membranes containing the microdomain markers alkaline phosphatase and sphingomyelin. However, cholesterol was resistant to Lubrol WX solubilization, whereas it was only marginally resistant to solubilization by Triton X-100. The microdomain marker caveolin-1 was localized to the canalicular plasma membrane domain and was resistant to Lubrol WX, but to a large extent solubilized by Triton X-100. The two additional microdomain markers, reggie-1 and reggie-2, were localized to the basolateral and canalicular plasma membrane and were partially resistant to Lubrol WX but resistant to Triton X-100. The canalicular transporters bile salt export pump, multidrug resistance protein 2, multidrug resistance-associated protein 2, and Abcg5 were largely resistant to Lubrol WX but were solubilized by Triton X-100. Conclusion: These results indicate the presence of two different types of microdomains in the canalicular plasma membrane: “Lubrol-microdomains” and “Triton-microdomains”. “Lubrol-microdomains” contain the machinery for canalicular bile formation and may be the starting place for canalicular lipid secretion. (Hepatology 2009.)
Elevations in alanine aminotransferase levels late in the course of antiviral therapy in hepatitis C virus RNA–negative patients are associated with virological relapse # †
Authors: Basso Monica , Giannini Edoardo G. , Torre Francesco , Blanchi Sabrina , Savarino Vincenzo , Picciotto Antonino 
Published: December 2008

Abstract
The incidence and clinical meaning of elevated alanine aminotransferase (ALT) in chronic hepatitis C patients who are hepatitis C virus (HCV)-RNA negative during pegylated interferon (PEG-IFN) and ribavirin therapy have not been completely characterized. In this study our aim was to assess the incidence, pattern, predictive factors, and clinical meaning of elevated ALT in a cohort of 173 chronic hepatitis C patients who obtained viral clearance during either PEG-IFNα2a or α2b and weight-based ribavirin therapy. Patients were defined sustained viral responders (SVRs) or relapser responders (RRs) on the basis of a serum HCV-RNA result at 24-week follow-up. SVR and RR were obtained in 141 (58%) and 32 patients (13%), respectively. Among the 173 study patients, 57 patients (33%) had undetectable serum HCV-RNA and elevated ALT in at least one evaluation (weeks 2, 4, 12, 24 in all genotypes, and week 48 in HCV genotype 1 and 4 alone), and this phenomenon was not differently distributed between SVRs and RRs. No pretreatment demographic (age, gender), clinical (ALT levels, histological grade and stage, body mass index) and viral (load, genotype) parameter was associated with this phenomenon. The incidence of elevated ALT levels was not associated with type of PEG-IFN and ribavirin dose. Elevated ALT levels showed a different longitudinal pattern, occurring more frequently between week 12 and the end of treatment in RR as compared to SVR patients (90% versus 9%, P = 0.000001). Conclusion: The occurrence of elevated ALT levels in HCV-RNA-negative patients during PEG-IFN and ribavirin therapy is a fairly frequent and unpredictable phenomenon. Although ALT elevation per se is not associated with a greater risk of relapse, its occurrence in the later phases of therapy is more common in relapsing patients. (Hepatology 2009.)
Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride #
Authors: Park Ogyi , Jeong Won-IL , Wang Lei , Wang Hua , Lian Zhe-Xiong , Gershwin Eric M. , Gao Bin 
Published: December 2008

Abstract
Liver fibrosis is a common scarring response to all forms of chronic liver injury and is always associated with inflammation that contributes to fibrogenesis. Although a variety of cell populations infiltrate the liver during inflammation, it is generically clear that CD8 T lymphocytes promote while natural killer (NK) cells inhibit liver fibrosis. However, the role of invariant natural killer T (iNKT) cells, which are abundant in the liver, in hepatic fibrogenesis, remains obscure. Here we show that iNKT-deficient mice are more susceptible to carbon tetrachloride (CCl4)-induced acute liver injury and inflammation. The protective effect of naturally activated iNKT in this model is likely mediated via suppression of the proinflammatory effect of activated hepatic stellate cells. Interestingly, strong activation of iNKT through injection of iNKT activator α-galactosylceramide (α-GalCer) accelerates CCl4-induced acute liver injury and fibrosis. In contrast, chronic CCl4 administration induces a similar degree of liver injury in iNKT-deficient and wild-type mice, and only a slightly higher grade of liver fibrosis in iNKT-deficient mice than wild-type mice 2 weeks but not 4 weeks after CCl4 injection, although iNKT cells are able to kill activated stellate cells. An insignificant role of iNKT in chronic liver injury and fibrosis may be attributable to hepatic iNKT cell depletion. Finally, chronic α-GalCer treatment had little effect on liver injury and fibrosis, which is attributable to iNKT tolerance after α-GalCer injection. Conclusion: Natural activation of hepatic iNKT cells inhibits, whereas strong activation of iNKT cells by α-GalCer accelerates CCl4-induced acute liver injury, inflammation, and fibrosis. During chronic liver injury, hepatic iNKT cells are depleted and play a role in inhibiting liver fibrosis in the early stage but not the late stage of fibrosis. (Hepatology 2009.)
Circulating prediagnostic interleukin‐6 and C‐reactive protein and prostate cancer incidence and mortality
Authors: Stark Jennifer Rider , Li Haojie , Kraft Peter , Kurth Tobias , Giovannucci Edward L. , Stampfer Meir J. , Ma Jing , Mucci Lorelei A. 
Published: December 2008

AbstractInterleukin‐6 (IL‐6) and C‐reactive protein (CRP) are elevated in prostate cancer patients, but the role of prediagnostic levels of these inflammatory mediators on prostate cancer outcomes is unclear. We undertook a large, prospective case‐control study to evaluate the relation between prediagnostic levels of IL‐6 and CRP and prostate cancer incidence and mortality. We also investigated the role of the IL‐6 (−174 G/C) polymorphism in relation to circulating levels of IL‐6 and CRP, as well as cancer risk and mortality. We used unconditional logistic regression that adjusted for matching factors to analyze prostate cancer risk. For analyses of prostate cancer mortality, we conducted survival analyses in cases. Because of the strong link between inflammatory markers and body mass index (BMI), we assessed interactions between BMI and plasma levels on prostate cancer outcomes. Neither IL‐6 nor CRP plasma levels varied significantly by IL‐6 genotype. Genotype was not associated with prostate cancer risk or survival. Though neither IL‐6 nor CRP was associated with prostate cancer incidence overall, we observed a statistically significant interaction between IL‐6 and BMI on prostate cancer incidence (pinteraction < 0.01). Increasing IL‐6 levels were positively associated with risk in healthy weight men, but inversely associated with risk in overweight men. Further, prediagnostic IL‐6 was associated with time to prostate cancer progression/death among healthy weight prostate cancer cases (ptrend = 0.02). Adjusted hazard ratios were 1.73 (95% CI: 0.86, 3.51) comparing the highest to lowest IL‐6 level. Our study suggests that IL‐6 may potentially be involved in the development or progression of prostate cancer. © 2008 Wiley‐Liss, Inc.
Fatty acid synthase is over‐expressed in large aberrant crypt foci in rats treated with azoxymethane
Authors: Lau Dominic S.Y. , Archer Michael C. 
Published: December 2008

AbstractFatty acid synthase (FAS) is over‐expressed in many human cancers including colon. High levels of FAS expression have also been observed in a number of lesions that are precursors to invasive colorectal cancer. However, FAS expression in aberrant crypt foci (ACF), the earliest identifiable lesions in colon cancer development, has not been investigated. In this study, we treated Fisher rats with a single dose of the colon carcinogen azoxymethane then evaluated ACF 100 days later. We showed that large ACF (≥4 crypts/focus) have a significantly higher level of immunohistochemical staining for FAS than either small ACF (≤3 crypts/focus) or normal crypts. Furthermore, the severity of nuclear atypia in ACF was positively associated with increased expression of FAS. These findings suggest that the genes associated with FAS over‐expression are activated early in the stepwise development of colon cancer, though not until the ACF have reached a critical size with a level of nuclear atypia indicative of dysplasia. © 2008 Wiley‐Liss, Inc.
Liposomal honokiol inhibits VEGF‐D‐induced lymphangiogenesis and metastasis in xenograft tumor model
Authors: Wen Jing , Fu A‐fu , Chen Li‐Juan , Xie Xing‐Jiang , Yang Guang‐Li , Chen Xian‐Cheng , Wang Yong‐Sheng , Li Jiong , Chen Ping , Tang Ming‐Hai , Shao Xi Ming , Lu You , Zhao Xia , Wei Yu‐Quan 
Published: December 2008

AbstractLymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor‐D may play an important role in promoting tumor metastasis to regional lymph nodes and these processes can be inhibited by inactivation of the VEGFR‐3 signaling pathway. Honokiol has been reported to possess potent antiangiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor‐associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we established lymph node metastasis models by injecting overexpressing VEGF‐D Lewis lung carcinoma cells into C57BL/6 mice to explore the effect of honokiol on tumor‐associated lymphangiogenesis and related lymph node metastasis. The underlying mechanisms were systematically investigated in vitro and in vivo. In in vivo study, liposomal honokiol significantly inhibited the tumor‐associated lymphangiogenesis and metastasis in Lewis lung carcinoma model. A remarkable delay of tumor growth and prolonged life span were also observed. In in vitro study, honokiol inhibited VEGF‐D‐induced survival, proliferation and tube‐formation of both human umbilical vein endothelial cells (HUVECs) and lymphatic vascular endothelial cells (HLECs). Western blotting analysis showed that liposomal honokiol‐inhibited Akt and MAPK phosphorylation in 2 endothelial cells, and downregulated expressions of VEGFR‐2 of human vascular endothelial cells and VEGFR‐3 of lymphatic endothelial cells. Thus, we identified for the first time that honokiol provided therapeutic benefit not only by direct effects on tumor cells and antiangiogenesis but also by inhibiting lymphangiogenesis and metastasis via the VEGFR‐3 pathway. The present findings may be of importance to investigate the molecular mechanisms underlying the spread of cancer via the lymphatics and explore the therapeutical strategy of honokiol on antilymphangiogenesis and antimetastasis. © 2008 Wiley‐Liss, Inc.
Ag‐doped manganite nanoparticles: New materials for temperature‐controlled medical hyperthermia
Authors: Melnikov O. V. , Gorbenko O. Yu. , M̌arkelova M. N. , Kaul A. R. , Atsarkin V. A. , Demidov V. V. , Soto C. , Roy E. J. , Odintsov B. M. 
Published: December 2008

AbstractThe purpose of this study was to introduce newly synthesized nanomaterials as an alternative to superparamagnetic ironoxide based particles (SPIO) and thus to launch a new platform for highly controllable hyperthermia cancer therapy and imaging. The new material that forms the basis for this article is lanthanum manganite particles with silver ions inserted into the perovskite lattice: La1−xAgxMnO3+δ. Adjusting the silver doping level, it is possible to control the Curie temperature (Tc) in the hyperthermia range of interest (41–44°C). A new class of nanoparticles based on silver‐doped manganites La1–xAgxMnO3+δ is suggested. New nanoparticles are stable, and their properties were not affected by the typical ambient conditions in the living tissue. It is possible to monitor the particle uptake and retention by MRI. When these particles are placed into an alternating magnetic field, their temperature increases to the definite value near Tc and then remains constant if the magnetic field is maintained. During the hyperthermia procedure, the temperature can be restricted, thereby preventing the necrosis of normal tissue. A new class of nanoparticles based on silver‐doped manganites La1–xAgxMnO3+δ was suggested. Ag‐doped perovskite manganites particles clearly demonstrated the effect of adjustable Curie temperature necessary for highly controllable cellular hyperthermia. The magnetic relaxation properties of the particles are comparable with that of SPIO, and so we were able to monitor the particle movement and retention by MRI. Thus, the new material combines the MRI contrast enhancement capability with targeted hyperthermia treatment. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
In vivo production of nanosized metal wear debris formed by tribochemical reaction as confirmed by high‐resolution TEM and XPS analyses
Authors: Milošev Ingrid , Remškar Maja 
Published: December 2008

AbstractHigh‐resolution transmission electron microscopy (TEM) and X‐ray photoelectron spectroscopy (XPS) were used to establish the link between particles isolated from periprosthetic tissue of metal‐on‐metal (MOM) bearing and the solid deposit at the surface of retrieved MOM hip components. The high resolution of TEM made it possible to identify individual CoCrMo wear particles. Two shapes were observed. Needle‐shaped particles ranged from 40 to 120 nm and contained both Co and Cr. Globular particles ranged up to 90 nm and contained high levels of Cr and no Co. Ti‐ and Ca‐based particles were also identified. XPS analysis of the areas of thick solid deposit on the retrieved femoral head showed that the base alloy was covered by up to nearly 1‐μm thick layer containing carbon, nitrogen, and oxygen. This layer was organic in nature, presumably protein‐related. In areas with a thinner deposit, an organic‐related layer was mixed with layers of metal oxides, the latter being much thinner than the extensive organic, carbon‐rich layer. Outside the area of the deposit, the passive oxidized chromium layer was thinner, less than 20 nm, and carbon was bound to nonorganic oxygen. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Polymeric particle formation through electrospraying at low atmospheric pressure
Authors: Wu Yiquan , Kennedy Scott J. , Clark Robert L. 
Published: December 2008

AbstractElectrospraying is a simple and versatile technique capable of producing polymeric particles. However, most investigations carried out thus far have been performed at ambient atmospheric pressure without studying the influences of pressure on the formation of polymeric particles. Here, we report our investigation on the effects of varying the pressure and the solution concentration on the microstructures of electrosprayed polymeric particles. Pressures are varied from ambient atmospheric pressure to 380 mmHg below ambient pressure, and solution concentrations are varied over a range of 3–7 w/v %. By varying these parameters, we manipulated the rate of solvent evaporation and the solidification of the electrosprayed particles. The results show that changes to the pressure had significant effects on the microstructure and morphology of poly(ε‐caprolactone) (PCL) particles. The average particle size became larger as the chamber pressure decreased. At a solution concentration of 5 w/v % and a pressure 150 mmHg below ambient pressure, uniform and spherical PCL particles were generated. Electrospun fibers were formed when a solution concentration of 7 w/v % was used. The developed technique can be applied to prepare polymeric drug delivery carriers though a low‐pressure‐assisted spray‐drying method, and is particularly suitable for fabricating delivery microspheres encapsulated with temperature‐sensitive drugs and biomolecules. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Biomechanical and histomorphometric evaluation of a thin ion beam bioceramic deposition on plateau root form implants: An experimental study in dogs
Authors: Granato Rodrigo , Marin Charles , Suzuki Marcelo , Gil Jose N. , Janal Malvin N. , Coelho Paulo G. 
Published: December 2008

AbstractThe aim of this study was to evaluate the biomechanical fixation, bone‐to‐implant contact, and bone morphology of an ion beam assisted deposition of a 300–500 nm thick Ca‐ and P‐based bioceramic surface on a previously alumina‐blasted/acid‐etched Ti‐6Al‐4V implant surface in a dog model. Materials and Methods: Thirty‐six 4.5 × 11 mm plateau root form implants, control (alumina‐blasted/acid‐etched‐AB/AE) and test groups (AB/AE+300–500 nm bioceramic coating, Nanotite™) were placed along a proximal tibia of six beagle dogs remaining for 2 and 4 weeks (n = 3 animals per implantation time). Following euthanization, the implants were torqued to interface fracture at ∼0.196 radians/sec until a 10% maximum load drop was detected. The implants in bone were nondecalcified processed to ∼30 μm thickness slides for histomorphologic and bone‐to‐implant contact (BIC) assessment. Statistical analyses for torque to interface fracture were performed using a mixed model ANOVA, and BIC was evaluated by the χ2 test at 95% level of significance. Results: At 4 weeks, significantly higher torque to interface fracture was observed for the Test implant surface. Histomorphologic analysis showed higher degrees of bone organization for test implants compared to control at 2 and 4 weeks. Significantly higher BIC was observed at 4 weeks compared to 2 weeks (no statistical differences between control and test implants). Conclusion: The higher torque to interface fracture and increased bone maturity obtained in this study support that the surface modification comprising a 300–500 nm Ca‐ and P‐based bioceramic coating positively influenced healing around pleateau root form implants. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Feeding kinematics and performance of Hawaiian stream gobies, Awaous guamensis and Lentipes concolor: Linkage of functional morphology and ecology
Authors: Maie Takashi , Wilson Megan P. , Schoenfuss Heiko L. , Blob Richard W. 
Published: December 2008

AbstractDistributions of Hawaiian stream fishes are typically interrupted by waterfalls that divide streams into multiple segments. Larvae hatch upstream, are flushed into the ocean, and must climb these waterfalls to reach adult habitats when returning back to freshwater as part of an amphidromous life cycle. Stream surveys and studies of climbing performance show that Lentipes concolor Gill can reach fast‐flowing upper stream segments but that Awaous guamensis Valenciennes reaches only slower, lower stream segments. Gut content analyses for these two species indicate considerable overlap in diet, suggesting that feeding kinematics and performance of these two species might be comparable. Alternatively, feeding kinematics and performance of these species might be expected to differ in relation to the different flow regimes in their habitat (feeding in faster stream currents for L. concolor versus in slower currents for A. guamensis). To test these alternative hypotheses, we compared food capturing kinematics and performance during suction feeding behaviors of A. guamensis and L. concolor using morphological data and high‐speed video. Lentipes concolor showed both a significantly larger gape angle and faster jaw opening than A. guamensis. Geometric models calculated that despite the inverse relationship of gape size and suction pressure generation, the fast jaw motions of L. concolor allow it to achieve higher pressure differentials than A. guamensis. Such elevated suction pressure would enhance the ability of L. concolor to successfully capture food in the fast stream reaches it typically inhabits. Differences in jaw morphology may contribute to these differences in performance, as the lever ratio for jaw opening is about 10% lower in L. concolor compared with A. guamensis, suiting the jaws of L. concolor better for fast opening. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.
Morphology of the skull of the white‐nosed blindsnake, Liotyphlops albirostris (Scolecophidia: Anomalepididae)
Authors: Rieppel Olivier , Kley Nathan J. , Maisano Jessica Anderson 
Published: December 2008

AbstractThis article presents a detailed description and illustration of the skull of Liotyphlops albirostris in comparison to the skulls of Typhlophis squamosus, Leptotyphlops dulcis, and Typhlops jamaicensis, based on high‐resolution X‐ray computed tomography (HRXCT). The skull of T. squamosus is illustrated and discussed in detail for the first time. A number of uniquely shared derived characters is identified that support the monophyly of the clade Anomalepididae. Anomalepidids retain some features that are plesiomorphic relative to other scolecophidians, such as the presence of a supratemporal (except in Anomalepis) and ectopterygoid. The homology of the element located posteroventral to the eyeball in anomalepidids and variably referred to as a jugal or postorbital (or a fusion of both in Anomalepis) remains unknown. Scolecophidians exhibit a highly derived skull morphology adapted to head‐first burrowing. Both anomalepidids and typhlopids evolved a condition known as an “outer shell design,” but did so in different ways. Leptotyphlopids combine elements of both the anomalepidid and typhlopid snout morphologies. J. Morphol., 2009. © 2008 Wiley‐Liss, Inc.