bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Sprouty2 stability by mammalian Seven‐in‐Absentia homolog 2
Authors: Nadeau Robert J. , Toher Jessica L. , Yang Xuehui , Kovalenko Dmitry , Friesel Robert
Published: August 2006

Mammalian Sprouty (Spry) gene expression is rapidly induced upon activation of the FGF receptor signaling pathway in multiple cell types including cells of mesenchymal and epithelial origin. Spry2 inhibits FGF‐dependent ERK activation and thus Spry acts as a feedback inhibitor of FGF‐mediated proliferation. In addition, Spry2 interacts with the ring‐finger‐containing E3 ubiquitin ligase, c‐Cbl, in a manner that is dependent upon phosphorylation of Tyr55 of Spry2. This interaction results in the poly‐ubiquitination and subsequent degradation of Spry2 by the proteasome. Here, we describe the identification of another E3 ubiquitin ligase, human Seven‐in‐Absentia homolog‐2 (SIAH2), as a Spry2 interacting protein. We show by yeast two‐hybrid analysis that the N‐terminal domain of Spry2 and the ring finger domain of SIAH2 mediated this interaction. Co‐expression of SIAH2 resulted in proteasomal degradation of Spry1, 2, and to a lesser extent Spry4. The related E3 ubiquitin‐ligase, SIAH1, had little effect on Spry2 protein stability when co‐expressed. Unlike c‐Cbl‐mediated degradation of Spry2, SIAH2‐mediated degradation was independent of phosphorylation of Spry2 on Tyr55. Spry2 was also phosphorylated on Tyr227, and phosphorylation of this residue was also dispensable for SIAH2‐mediated degradation of Spry2. Finally, co‐expression of SIAH2 with Spry2 resulted in a rescue of FGF2‐mediated ERK phosphorylation. These data suggest a novel mechanism whereby Spry2 stability is regulated in a manner that is independent of tyrosine phosphorylation, and provides an addition level of control of Spry2 protein levels. J. Cell. Biochem. 100: 151–160, 2007. © 2006 Wiley‐Liss, Inc.
TGFβ inducible early gene‐1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway
Authors: Rajamannan Nalini M. , Subramaniam Malayannan , Abraham Theodore P. , Vasile Vlad C. , Ackerman Michael J. , Monroe David G. , Chew Teng‐Leong , Spelsberg Thomas C.
Published: August 2006

Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFβ inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG−/− knock‐out mouse was studied. Male mice age 4–16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG−/− knock‐out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG−/−, and an increase in wall thickness in TIEG−/− mice of (1.85 ± 0.21 mm), compared to the control (1.13 ± 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG−/− heart tissues expressed a 13.81‐fold increase in pituitary tumor‐transforming gene‐1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG−/− mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse. J. Cell. Biochem. 100: 315–325, 2007. © 2006 Wiley‐Liss, Inc.
Functional analysis of survivin in spindle assembly in Xenopus egg extracts
Authors: Canovas Pedro M. , Guadagno Thomas M.
Published: August 2006

Survivin is a member of the inhibitor of apoptosis (IAP) protein family that serves critical roles in mitosis and cytokinesis. Many studies have suggested Survivin's involvement in spindle regulation, but direct biochemical evidence for this has been lacking. Using the cell‐free system of Xenopus egg extracts, we tested whether Survivin was necessary for the assembly of metaphase spindles. Removal or inhibition of Xenopus Survivin causes the disruption in the formation of metaphase spindles. In particular, we observe the generation of microtubule (MT) asters or poorly formed shortened spindle structures. In the latter phenotype the spindle structures display a decrease pole‐to‐pole length and a reduction of MTs around the chromatin indicating that Survivin may promote the stabilization of MT–chromatin interactions. In addition, function analysis of Survivin's conserved phosphorylation site Thr34 (Thr43 in Xenopus) and tubulin‐binding domain was also assessed in regulating spindle assembly. Treatment of Xenopus egg extracts with a recombinant Survivin mutant that contained an alanine residue substitution at Thr43 (SURT43A mutant) or that was missing the C‐terminal tubulin‐binding domain (SURCL mutant) produced an increased frequency of MT asters and shorten abnormal spindle structures in Xenopus egg extracts. Interestingly, a phosphomimetic mutation made at residue Thr43 of Survivin (SURT43E mutant) generated a high frequency of MT asters implying that premature ‘activation’ of Survivin may interfere with an early stage of spindle assembly. Taken together, we propose that Survivin is a necessary component of the mitotic spindle and its phosphorylation at residue Thr43 is important for Survivin function in spindle assembly. J. Cell. Biochem. 100: 217–229, 2007. © 2006 Wiley‐Liss, Inc.
Extreme sensitivity to Yondelis® (Trabectedin, ET‐743) in low passaged sarcoma cell lines correlates with mutated p53
Authors: Moneo Victoria , Serelde Beatriz G. , Fominaya Jesús , Leal Juan F.M. , Blanco‐Aparicio Carmen , Romero Lourdes , Sánchez‐Beato Margarita , Cigudosa Juan C. , Tercero Juan C. , Piris Miguel A. , Jimeno Jose , Carnero Amancio
Published: August 2006

Yondelis® (Trabectedin, ET‐743) is a marine anticancer agent currently in Phase II/III development in patients with advanced pretreated soft tissue sarcoma. In the present study, we generated a panel of low passaged tumor cell lines from samples explanted from chemonaive sarcoma patients with different tumor types. We assessed in vitro sensitivity/resistance to Trabectedin and doxorubicin in a panel of sarcoma cell lines and examined the correlation between molecular alterations in DNA repair genes and sensitivity to Trabectedin. We treated cell lines with Trabectedin and doxorubicin in both 96‐h and clonogenic assays. In both assays, well‐defined groups of resistant and sensitive cell lines were observed. Resistance to Trabectedin did not correlate with resistance to doxorubicin, indicating that the two drugs may have different mechanisms of resistance. p53 mutations and deletions correlated with extreme sensitivity (IC50 < 1 nM) to Trabectedin (P < 0.01). In a pair of isogenic cell lines differing only in the presence or absence of wild‐type p53, the absence of p53 rendered cells threefold more sensitive to Trabectedin. J. Cell. Biochem. 100: 339–348, 2007. © 2006 Wiley‐Liss, Inc.
Interleukin‐1β and tetradecanoylphorbol acetate‐induced biosynthesis of tumor necrosis factor α in human hepatoma cells involves the transcription factors ATF2 and c‐Jun and stress‐activated protein kinases
Authors: Bauer Inge , Al Sarraj Jude , Vinson Charles , Larsen Reinhard , Thiel Gerald
Published: August 2006

The proinflammatory cytokine tumor necrosis factor (TNF) α is mainly produced in cells from the monocyte/macrophage lineage. TNFα is also a key signaling molecule in the liver functioning as an important physiological and pathogenic mediator. In hepatocytes or human hepatoma cells TNFα is expressed at extremely low levels but TNFα biosynthesis can be induced by interleukin (IL)‐1β or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Here, we show that IL‐1β and TPA stimulated TNFα gene transcription in hepatoma cells mediated by a composite TPA‐responsive element/cAMP response element. Both IL‐1β and TPA triggered phosphorylation and activation of the basic region leucine zipper transcription factors c‐Jun and ATF2 and expression of dominant‐negative mutants of c‐Jun and ATF2‐reduced TNFα promoter activity and secretion of TNFα. Expression of the nuclear dual‐specific MAP kinase phosphatase‐1 (MKP‐1) blocked TNFα promoter activity and TNFα secretion following IL‐1β or TPA stimulation, indicating that MKP‐1 functions as a nuclear shut‐of‐device of IL‐1β and TPA‐induced TNFα expression. J. Cell. Biochem. 100: 242–255, 2007. © 2006 Wiley‐Liss, Inc.
Germinal vesicle chromatin configurations of bovine oocytes
Authors: Liu Yong , Sui Hong‐Shu , Wang Hui‐Li , Yuan Ji‐Hong , Luo Ming‐Jiu , Xia Ping , Tan Jing‐He
Published: August 2006

A common feature in the configuration of germinal vesicle (GV) chromatin in most species is that diffuse chromatin condenses into a perinucleolar ring during follicular growth; however, no such ring was observed in goat oocytes. Reports on whether bovine GV chromatin condenses into a perinucleolar ring are controversial. Besides, it is not known whether the perinucleolar ring in an oocyte represents a step toward final maturation or atresia. Changes in GV chromatin configurations during growth and maturation of bovine oocytes were studied using a new method that allows a clearer visualization of both the nucleolus and the chromatin after Hoechst and chromomycin A3staining. On the basis of the degree of condensation and distribution, the GV chromatin of bovine oocytes were classified into five configurations: NSN with diffuse chromatin in the whole nuclear area, N with condensed netlike chromatin, C with clumped chromatin, SN with clumped chromatin surrounding the nucleoli, and F with floccular chromatin near the nucleoli and near the nuclear envelope. Most of the oocytes were at the NSN stage in the <1.4‐mm follicles, but the NSN pattern disappeared completely in follicles larger than 1.5mm. The SN pattern began to emerge in 1.5‐mm follicles, and the number of SN oocytes increased while the number of oocytes with N and C configurations decreased with follicular growth. During maturation in vivo, while the number of N, C, and SN oocytes decreased, that of the F oocytes increased and reached maximum at 51h post prostaglandin injection. After that, the number of F oocytes decreased significantly because of germinal vesicle breakdown (GVBD). During maturation in vitro, GV chromatin configurations changed in a similar manner as during maturation in vivo. Fewer oocytes were at N, C, and SN stages, but more were at F and GVBD stages in the atretic than in the healthy follicles. Serum starvation slowed the F‐GVBD transition of the in vitro maturing oocytes. More oocytes were of the SN or C configuration when ovaries were transported at 45–40°C than at 35–30°C. Most of the heated oocytes were blocked at the SN stage during in vitro maturation. It is concluded that (i) bovine GV chromatin condenses into a perinucleolar ring during follicular growth; (ii) bovine oocytes were synchronized at the F stage before GVBD; (iii) oocyte GV chromatin configurations were affected by serum starvation, high temperature, and follicular atresia. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Atomic force microscopy characterization of Xenopus laevis oocyte plasma membrane
Authors: Orsini F. , Santacroce M. , Perego C. , Lenardi C. , Castagna M. , Mari S.A. , Sacchi V.F. , Poletti G.
Published: August 2006

We used atomic force microscopy (AFM) to characterize the plasma membrane of Xenopus laevis oocytes. The samples were prepared according to novel protocols, which allowed the investigation of the extra‐ and intracellular sides of the membrane, both of which showed sparsely distributed spherical‐like protrusions. Regions with comparably sized and densely packed structures arranged in an orderly manner were visualized and dimensionally characterized. In particular, two different arrangements, hexagonal and square packing, were recognizable in ordered regions. The lateral dimension of structures visualized on the external side had a normal distribution centered on 25.5 ± 0.3 nm (mean value ± SE), whereas that on the intracellular side showed a normal distribution centered on 30.2 ± 0.8 nm. The height of the protrusions was 2–5 nm on the external side and 1–3 nm on the intracellular side. The mean number of structures on the external and intracellular sides of the plasma membrane was about 1000 μm−2 and 850 μm−2 respectively. Trypsin treatment greatly decreased the size of the membrane protrusions, thus confirming the proteic nature of the structures. These results show that AFM is a useful tool for structural characterization of proteins in a native eukaryotic membrane. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Sensilla and secretory glands in the antennae of a primitive ant: Dinoponera lucida (Formicidae: Ponerinae)
Authors: Marques‐Silva Solange , Matiello‐Guss Cirlei P. , Delabie Jacques H.C. , Mariano Cléa S.F. , Zanuncio José C. , Serrão José Eduardo
Published: August 2006

Morphology of the antennae of the female workers of the ponerine ant Dinoponera lucida was examined by light and scanning electron microscopy. In several antennomers, we found secretory gland cells of class I and III. Class III gland cells release their secretion through single pores in the antennal surface, whereas class I secretory cells are seen as tall epidermal cells close to the cuticle. Both gland types have weak reaction for total proteins and neutral polysaccharides. Six distinct sensilla types were observed: trichodea, chaetica, campaniform, basiconica, placodea, and coeloconica. The possible sensory functions of these sensilla and the gland functions are discussed. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of a femtosecond fiber laser for two‐photon fluorescence correlation spectroscopy
Authors: Unruh Jay R. , Price E. Shane , Molla Roque G. , Hui Rongqing , Johnson Carey K.
Published: August 2006

This work evaluates a femtosecond fiber laser for use in two‐photon fluorescence fluctuation spectroscopy. Fiber lasers present an attractive alternative to Ti:Sapphire systems because of their compact size and portability. Autocorrelation of the second harmonic generation signal from the laser demonstrates that its stability is sufficient for two‐photon fluorescence correlation spectroscopy. Fluorescence correlation spectroscopy autocorrelation traces were well fit by a Gaussian–Lorentzian squared model with a beam waist near the diffraction limit for the 810 nm wavelength. A photon counting histogram collected with this system also fit nicely to a single‐species model, further demonstrating the quality of the focal shape. The authors conclude that the output from the femtosecond fiber laser is sufficiently stable and has a high enough quality beam shape for fluctuation fluorescence methods, and thus represents an effective, compact, readily portable two‐photon excitation source. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Adult celiac disease: What is the role of MRI?
Authors: Tomei Ernesto , Semelka Richard C. , Braga Larissa , Laghi Andrea , Paolantonio Pasquale , Marini Mario , Passariello Roberto , Di Tola Marco , Sabbatella Luigi , Picarelli Antonio
Published: August 2006

Purpose

To evaluate the ability of MRI to identify intra‐ and extraintestinal findings of celiac disease in an adult population.

Materials and Methods

Forty‐one subjects (18 men and 23 women; mean age = 41.3 years; 31 with biopsy‐proven celiac disease, and 10 healthy volunteers) underwent MRI of the small bowel. MR studies were performed on a 1.5‐T magnet using T2‐weighted half‐Fourier single‐shot turbo spin‐echo (HASTE) and true fast imaging in steady‐state precession (True‐FISP) sequences. The MR features and sensitivity, and the specificity and accuracy of some of these features are described.

Results

In the 31 celiac patients, MRI showed bowel dilatation in 61.3% (N = 19), increased number of ileal folds in 48.4% (N = 15), reversed fold pattern abnormality in 38.7% (N = 12), increased wall thickness in 16.1% (N = 5), duodenal stenosis in 6.5% (N = 2), intussusception in 12.9% (N = 4), mesenteric lymphadenopathy in 41.9% (N = 13), mesenteric vascular changes in 22.6% (N = 7), ascites in 6.5% (N = 2), and no abnormalities in 12.9% (N = 4). The volunteers had unremarkable exams. The overall specificity and accuracy were 100%, and sensitivity was 79% and 75% for increased number of ileal folders and reversed fold pattern abnormality, respectively.

Conclusion

MRI is able to demonstrate intra‐ and extraintestinal features that may lead to the diagnosis of celiac disease in adults. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Emerging techniques: Whole‐body screening and staging with MRI
Authors: Lauenstein Thomas C. , Semelka Richard C.
Published: August 2006

Strategies for screening or tumor staging include various modalities such as plain radiography, computed tomography (CT), MRI, and ultrasound. Technical innovations have created the feasibility to use MRI to image the entire body in a relatively short time‐period. Whole‐body MRI may play a potentially important role in evaluating for cancer or vascular disease. This article describes the rationale for using MRI to display the entire body, the techniques employed in whole‐body MRI, possibilities and limitations, and summarizes first clinical results for screening and staging purposes. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Quantitative measurements of regional lung ventilation using helium‐3 MRI in a methacholine‐induced bronchoconstriction model
Authors: Mosbah Karim , Crémillieux Yannick , Adeleine Patrice , Dupuich David , Stupar Vasile , Nemoz Chantal , Canet Emmanuelle , Berthezène Yves
Published: August 2006

Purpose

To demonstrate ventilation changes in an animal model of methacholine‐induced bronchoconstriction using hyperpolarized (HP) helium‐3 (He‐3) MRI.

Materials and Methods

Bronchoconstriction was induced in 11 healthy rats using an intravenous injection of methacholine. The He‐3 was laser‐polarized using a custom‐built system. MRI studies were performed on a 2‐Tesla bore magnet. Coronal dynamic ventilation images were obtained using a single inhalation of the laser‐polarized He‐3 gas before and after methacholine injection. Ventilation image series were processed on a pixel‐by‐pixel basis to generate three regional ventilation parameters: gas flow rate, filling time, and maximum gas volume. Student's paired t‐test was used for analysis.

Results

Ventilation image series with a temporal resolution of 5 msec were obtained before and after methacholine challenge. Quantitative regional gas dynamic information demonstrated statistically significant differences between the baseline and constricted states. Following methacholine injection, the mean flow values were significantly lower for the right lung (RL) (P = 0.006) and left lung (LL) (P = 0.024), while the mean filling time was found to be greater (RL: P = 0.08, LL: P = 0.021). Gas volume values at maximum inspiration were found to be significantly lower after methacholine (RL: P = 0.002; LL: P = 0.036).

Conclusion

He‐3 MRI demonstrated and quantified regional ventilation changes in bronchoconstriction conditions in rats. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Feasibility of dynamic susceptibility contrast perfusion MR imaging at 3T using a standard quadrature head coil and eight‐channel phased‐array coil with and without SENSE reconstruction
Authors: Lupo Janine M. , Lee Michael C. , Han Eric T. , Cha Soonmee , Chang Susan M. , Berger Mitchel S. , Nelson Sarah J.
Published: August 2006

Purpose

To investigate changes in image and dynamic signal‐to‐noise ratios (SNRs) of the ΔR2* curve, as well as magnetic susceptibility‐induced artifacts between a standard quadrature head coil and an eight‐channel phased‐array coil with and without sensitivity‐encoding (SENSE) at 3T, compared to the current clinical standard head coil acquisition at 1.5T.

Materials and Methods

Dynamic susceptibility contrast (DSC) perfusion MRI was performed on 80 brain tumor patients using a gradient‐echo, echo‐planar imaging (EPI) sequence. Image and dynamic SNR were compared between 1.5T and 3T field strengths, a quadrature and eight‐channel phased‐array coil, and a conventional vs. partially parallel EPI acquisition with SENSE reconstruction. The amount of geometric distortion and signal dropout was quantified and compared between conventional and SENSE EPI acquisitions within the same exam at 3T.

Results

An initial 2.6‐fold elevation in dynamic SNR was observed in normal‐appearing white matter when doubling the field strength (P < 0.001), with an additional 1.7‐fold increase found when employing an eight‐channel phased‐array coil (P < 0.002). Compared to the standard 3T eight‐channel coil acquisition, the implementation of SENSE reduced the number of voxels experiencing large anterior shifts in the phase‐encode direction, lowered the volume of signal dropout by 2.0–11.5%, and allowed a 1.4‐fold increase in slice coverage, while only decreasing the dynamic SNR by 22%.

Conclusion

SENSE EPI at 3T yielded a significant improvement in dynamic SNR over the 1.5T acquisitions. A significant reduction in magnetic susceptibility‐induced artifacts was achieved with SENSE EPI compared to the standard EPI eight‐channel coil acquisition at 3T. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Hyperintense nodules on non‐enhanced T1‐weighted gradient‐echo magnetic resonance imaging of cirrhotic liver: Fate and clinical implications
Authors: Yu Jeong‐Sik , Lee Jei Hee , Park Mi‐Suk , Kim Ki Whang
Published: August 2006

Purpose

To investigate the fate of hyperintense hepatic nodules on nonenhanced T1‐weighted (T1w) gradient‐echo (GRE) magnetic resonance (MR) images in cirrhotic patients.

Materials and Methods

A total of 79 cirrhotic patients with hyperintense nodules (>5 mm) on precontrast opposed‐phase (repetition time (TR)/echo time (TE) = 140/2.7 msec) GRE images from initial MRI without T2‐weighted (T2w) hyperintensity or arterial hypervascularity were subjected to analysis of subsequent MR images obtained at intervals of 12–56 months (mean = 24.5 months). Multiplicity of hyperintense nodules (group A, up to 8; group B, >8) was correlated with follow‐up changes.

Results

Group B patients were younger (P = 0.003) than group A patients (mean = 47.5 and 56.2 years, respectively). In 66 group A patients, 39 out of 143 lesions (27%) were enlarged, including 20 malignantly transformed or borderline lesions. Of the 104 lesions (the eight largest lesions in each patient) in 13 group B patients, only three (2.9%) were enlarged. The results of best‐ and worst‐case analyses showed that overall the lesions were benign in 91% and 82% of patients, respectively.

Conclusion

T1w hyperintense nodules without T2w hyperintensity or arterial hypervascularity in the cirrhotic liver are benign in most cases. In younger patients with numerous macronodules, almost all of these lesions follow a benign course. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Focal Wallerian degeneration of the corpus callosum in large middle cerebral artery stroke: Serial diffusion tensor imaging
Authors: Gupta Rakesh K. , Saksena Sona , Hasan Khader M. , Agarwal Atul , Haris Mohammad , Pandey Chandra M. , Narayana Ponnada A.
Published: August 2006

Purpose

To detect lesion‐related focal Wallerian degeneration (WD) changes in different segments of the corpus callosum (CC) in patients with large middle cerebral arterial (MCA) territory stroke using diffusion tensor imaging (DTI).

Materials and Methods

Eight patients underwent DTI scans at three different time points: six to eight weeks, 10–12 weeks, and beyond six months of stroke onset. Eight healthy age‐matched controls were also scanned using the same protocol at three different time points. Region‐of‐interest (ROI) analysis was performed on seven segments of the CC to determine the fractional anisotropy (FA), mean diffusivity (MD), and corresponding callosal cross‐sectional areas.

Results

On repeated‐measures analysis of variance (ANOVA), a significant reduction in the FA values was observed from the first to the third study compared to controls, reflecting temporal degeneration in the rostrum, genu, rostral body, anterior midbody, and splenium of the CC. However, a significant temporal elevation in MD values was observed in only the rostral body and anterior midbody of the CC. This was associated with a significant region‐specific reduction in the cross‐sectional areas at time points beyond six months, and appears to be consistent with the loss of callosal structural components due to interruption of the cortico‐callosal fibers secondary to WD.

Conclusion

These results indicate that cortico‐callosal topographical changes exhibit a significant temporal decline in observed FA values that is suggestive of cortico‐callosal WD in patients with large MCA territory stroke. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of hepatic lesions and hepatic parenchyma using diffusion‐weighted echo‐planar MR with three values of gradient b‐factor
Authors: Moteki Takao , Horikoshi Hiroyuki
Published: August 2006

Purpose

To determine whether diffusion‐weighted echo‐planar (EP) MR images with very small, small, and large gradient b‐factors are useful in evaluating hepatic lesions and hepatic parenchyma.

Materials and Methods

Approximate values of the apparent diffusion coefficients for diffusion (D) and for flowing spins (D*) for 96 hepatic lesions (26 hepatocellular carcinomas [HCCs], 28 metastases, 26 hemangiomas, and 16 cysts) and the non‐lesion‐bearing regions of parenchyma in 78 livers (50 noncirrhotic and 28 cirrhotic) were calculated from EP images (modified for gradient b‐factors of 3, 50, and 300 second/mm2).

Results

Liver cysts and noncirrhotic livers showed statistically higher mean D* values than HCCs, hemangiomas, metastases, and cirrhotic livers (P < 0.05 on Scheffé post hoc analysis). Liver cysts showed statistically higher mean D values than HCCs, metastases, noncirrhotic livers, and cirrhotic livers (P < 0.05). Liver hemangiomas showed statistically higher mean D values than HCCs, noncirrhotic livers, and cirrhotic livers (P < 0.05).

Conclusion

The D* value in addition to the D value may be useful for evaluating the nature of diffusion and flowing spins in hepatic lesions and hepatic parenchyma. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Identification of microbial mixtures by LC‐selective proteotypic‐peptide analysis(SPA)
Authors: Lo Alan A.‐L. , Hu Anren , Ho Yen‐Peng
Published: August 2006

This paper describes a method—using a combination of LC‐MS/MS of selected bacteria‐specific peptides and database search—for determining the species of bacteria present in a mixture. We identified the proteotypic peptides that were associated with specific bacteria by searching protein databases for the LC‐MS/MS data. The retention time windows for specific peptide markers were used as an extra constraint so that the peptide markers of many bacterial species could be analyzed in a single LC‐selective proteotypic‐peptide analysis (SPA). We performed LC‐MS/MS analyses on the proteolytic digest of cell extracts and monitored only the selected marker peptide ions at given elution time windows. The corresponding bacterial species could be characterized when the selected peptides that eluted at expected elution windows were identified correctly from the database. We managed to identify up to eight bacterial species simultaneously during a single LC‐MS/MS analysis, as well as bacteria mixed in various abundances. Two marker ions having similar values of m/z, but obtained from two different bacterial samples, which would otherwise be selected as precursors within mass tolerance and would complicate the MS/MS data, were time‐resolved using LC and then used to correctly identify their bacterial sources. The coupling of selective MS/MS monitoring with separation methods, such as LC, provides a highly selective and accurate analytical method for characterizing complex mixtures of bacterial species. Copyright © 2006 John Wiley & Sons, Ltd.
Mass spectrometry assisted assignments of binding and cleavage sites of copper(II) and platinum(II) complexes towards oxidized insulin B chain
Authors: Hong Jin , Miao Ren , Zhao Chunmei , Jiang Jiang , Tang Huiwei , Guo Zijian , Zhu Longgen
Published: August 2006

Interaction of cis‐[Pt(en)(H2O)2]2+ and [CuL(H2O)]2+, where L is 2‐[bis(2‐aminoethyl)amino]ethanol, with oxidized insulin B chain in molar ratio of 1 : 1, 1 : 2 and 1 : 3 at pH 2.5 and 40 °C has been investigated by electrospray ionization mass spectrometry (ESI‐MS) and tandem mass spectrometry (MS/MS). The results show that the binding sites of the two complexes with oxidized insulin B chain are terminal NH2, imidazole groups of His5 and His10. The hydrolytic cleavage studies show that the [CuL(H2O)]2+, upon a pendant hydroxyl group of the ligand, selectively cleaves the peptide bonds at Gly8–Ser9, Asn3–Gln4 and Phe1–Val2, and the cis‐[Pt(en)(H2O)2]2+ only cleaves the peptide bond at His10–Leu11. This is the first report of cis‐[Pt(en)(H2O)2]2+‐promoted cleavage of His–X peptide bond. Copyright © 2006 John Wiley & Sons, Ltd.
Diastereomeric differentiation of peptides with CuII and FeII complexation in an ion trap mass spectrometer
Authors: Lagarrigue Mélanie , Bossée Anne , Afonso Carlos , Fournier Françoise , Bellier Bruno , Tabet Jean‐Claude
Published: August 2006

Complexation by transition metal ions (CuII and FeII) was successfully used to differentiate the diastereomeric YAGFL, YDAGFL and YDAGFDL pentapeptides by electrospray ionization‐ion trap mass spectrometry in the positive ion mode using low‐energy collision conditions. This distinction was allowed by the stereochemical effects due to the (D)Leu/(L)Leu and the (D)Ala/(L)Ala residues yielding various steric interactions which direct relative dissociation rate constants of the binary [(M − H) + MeII]+ complexes (Me = Cu or Fe) subjected to low‐energy, collision‐induced dissociation processes. The interpretation of the collision‐induced dissociation spectra obtained from the diastereomeric cationized peptides allowed the location of the deprotonated site(s), leading to the postulation of ion structures and fragmentation pathways for both the [(M − H) + CuII]+ and [(M − H) + FeII]+ complexes, which differed significantly. With CuII, consecutive fragmentations, initiated by the decarboxylation at C‐terminus, were favored relative to sequence product ions. On the other hand, with FeII, competitive fragmentations resulting in abundant sequence product ions and significant internal losses were preferred. This could be explained by different localizations of the negative charge, which directs the orientation of both the [(M − H) + CuII]+ and [(M − H) + FeII]+ binary complexes fragmentations. Indeed, the free negative charge of the [(M − H) + CuII]+ ions was mainly located at one oxygen atom: either at the C‐terminal carboxylic group or, to a minor extent, at the Tyr phenol group (i.e. zwitterionic forms). On the other hand, the negative charge of the [(M − H) + FeII]+ ions was mainly located at one of the nitrogen atoms of the peptide backbone and coordinated to FeII (i.e. salt non‐zwitterionic form).

Moreover, this study reveals the particular behavior of CuII reduced to CuI, which promotes radical losses not observed from the peptide–FeII complexes. Finally, this study shows the analytical potentialities of the complexation of transition metal ions with peptides providing structural information complementary to that obtained from low‐energy, collision‐induced dissociation processes of protonated or deprotonated peptides. Copyright © 2006 John Wiley & Sons, Ltd.
Mass spectrometric characterization of covalent modification of human serum albumin by 4‐hydroxy‐trans‐2‐nonenal
Authors: Aldini Giancarlo , Gamberoni Luca , Orioli Marica , Beretta Giangiacomo , Regazzoni Luca , Maffei Facino Roberto , Carini Marina
Published: August 2006

Several pieces of evidence indicate that albumin modified by HNE is a promising biomarker of systemic oxidative stress and that HNE‐modified albumin may contribute to the immune reactions triggered by lipid peroxidation‐derived antigens. In this study, we found by HPLC analysis that HNE is rapidly quenched by human serum albumin (HSA) because of the covalent adduction to the different accessible nucleophilic residues of the protein, as demonstrated by electrospray ionization mass spectrometry (ESI‐MS) direct infusion experiments (one to nine HNE adducts, depending on the molar ratio used, from 1 : 0.25 to 1 : 5 HSA : HNE). An LC‐ESI‐MS/MS approach was then applied to enzymatically digested HNE‐modified albumin, which permitted the identification of 11 different HNE adducts, 8 Michael adducts (MA) and 3 Schiff bases (SB), involving nine nucleophilic sites, namely: His67 (MA), His146 (MA), His242 (MA), His288 (MA), His510 (MA), Lys 195 (SB), Lys 199 (MA, SB), Lys525 (MA, SB) and Cys34 (MA). The most reactive HNE‐adduction site was found to be Cys34 (MA) followed by Lys199, which primarily reacts through the formation of a Schiff base, and His146, giving the corresponding HNE Michael adduct. These albumin modifications are suitable tags of HNE‐adducted albumin and could be useful biomarkers of oxidative and carbonylation damage in humans. Copyright © 2006 John Wiley & Sons, Ltd.
Structure elucidation of cyclic pyoverdins and examination of rearrangement reactions in MS/MS experiments by determination of exact product ion masses
Authors: Schäfer Mathias , Fuchs Regine , Budzikiewicz Herbert , Springer Andreas , Meyer Jean‐Marie , Linscheid Michael
Published: August 2006

Structure elucidation of naturally occurring linear and cyclic peptidic compounds can be complicated by rearrangement reactions induced upon collision activation (CA) when parts of the molecule migrate, suggesting incorrect substitution patterns. Such complex rearrangements are examined and discussed for two iron complexing compounds produced by the bacterial genus Pseudomonas (so‐called pyoverdins). Various MS2‐ and MS3‐product ion experiments were performed using a quadrupole‐ion trap (QIT) at low resolution and a FT‐ICR at high resolution allowing accurate mass determinations. The results of the multidimensional study confirm the proposed processes. On the basis of the series of tandem‐MS experiments the structure of a new pyoverdin from a P. fluorescens strain [PVD(D47)] is deduced. Copyright © 2006 John Wiley & Sons, Ltd.
Climatic outliers
Authors: Hunt B. G.
Published: August 2006

A 10 000‐year simulation for ‘present’ climate has been generated with the CSIRO Mark 2 coupled climatic model. In this paper the model output has been analysed to produce a climatology of climatic outliers and to assess the role of such outliers in climatic variability. An assessment of the frequency of occurrence of outliers, compared with the statistical expectation from a Gaussian distribution, indicates that over most of the globe the surface temperature conforms to this distribution, but this is not the case for rainfall. Among the issues considered are the spatial occurrence rates over the globe of normalised climatic anomalies of various magnitudes, the temporal variability of outliers, the seasonal variability for a given outlier year, the spatial characteristics of outliers and the question of precursors to outliers. The relationship of outliers to the El Niño/Southern Oscillation, the Pacific Decadal Oscillation and the North Atlantic Oscillation is also considered. A case study examining the relative severities of an outlier drought to a severe drought is also undertaken. Finally, the role of outliers and the greenhouse effect is considered. It is concluded that outliers are a manifestation of stochastic forcing. Copyright © 2006 Royal Meteorological Society.
Plant‐oil‐based lubricants and hydraulic fluids
Authors: Schneider Manfred P
Published: August 2006

It is estimated that, at present, approximately 50% of all lubricants sold worldwide end up in the environment via total loss applications, volatility, spills or accidents. More than 95% of these materials are currently mineral oil based. In view of their high ecotoxicity and low biodegradability, mineral oil‐based lubricants constitute a considerable threat to the environment. In contrast, most lubricants and hydraulic fluids based on plant oils are rapidly and completely biodegradable and are of low ecotoxicity; moreover, lubricants based on plant oils display excellent tribological properties and generally have very high viscosity indices and flashpoints. However, in order to compete with mineral‐oil‐based products, some of their inherent disadvantages must be corrected, such as their sensitivity to hydrolysis and oxidative attack, and their behaviour at low temperatures. Various methods to improve the undesirable properties of native plant oils will be discussed. In parallel, government regulations that encourage or enforce the use of bio‐based fluids, at least in ecologically sensitive areas, will help to increase their market share. Using the numerous possibilities for selective breeding and/or chemical improvement of the double bond systems of natural fatty acids by increased R&D, the major obstacles regarding the use of plant‐based raw materials for the production of lubricant base fluids can be overcome and bio‐based fluids should expect a future with increasing market shares. Copyright © 2006 Society of Chemical Industry
Solubility measurement of methyl anthranilate in supercritical carbon dioxide using dynamic and static equilibrium systems
Authors: Tsai Wen‐Chyan , Ruan Yonghong , Rizvi Syed SH
Published: August 2006

The solubility of methyl anthranilate in supercritical carbon dioxide was determined using dynamic and static equilibrium systems. Three temperatures (40, 60 and 80 °C) and a pressure range between 160 and 340 atm were applied for the dynamic solubility measurements. The flow rate was maintained at 0.5 mL min−1 in the dynamic solubility measurements, where the solute solubility was claimed to be independent of the flow‐rate factor. Two temperatures (40 and 60 °C) and the pressure range between 100 and 265 atm were used in the static equilibrium system. The crossover pressure region was observed between 220 and 240 atm in the static system, but was not seen in the dynamic system. The solubility of methyl anthranilate determined by the static system was consistently higher than the dynamic solubility measurement, indicating that the static technique provided more reliable solubility data for methyl anthranilate than the dynamic technique. The solubility data obtained with the static system were in good agreement with the predictive models based on the Chrastil equation and the Peng–Robinson equation of state with the Panagiotopoulos and Reid mixing rule. Copyright © 2006 Society of Chemical Industry
In vitro bioavailability of calcium and iron from selected green leafy vegetables
Authors: Gupta Sheetal , Lakshmi A Jyothi , Prakash Jamuna
Published: August 2006

The objective of the present investigation was to analyze the relative influence of oxalic acid, phytic acid, tannin and dietary fiber on in vitro availability of iron and calcium from green leafy vegetables (GLV). Thirteen GLV were selected and analyzed for iron, calcium, oxalic acid, phytic acid, tannin and dietary fiber contents using standard methods. The bioavailability of calcium and iron in the GLV was estimated by equilibrium dialysis. Oxalic acid content was less than 1 g kg−1 in four greens and ranged between 1.22 to 11.98 g kg−1 in the remaining. Dietary fiber ranged from 19.5 to 113.7 g kg−1. Tannin content ranged between 0.6138 and 2.1159 g kg−1 with the exception of two GLV that had 0.1332 and 14.8619 g kg−1. Four GLV were found to have approximately 40% bioavailable iron, while the others were in the range of 6–30%. In vitro available calcium was less than or equal to 25% in eight GLV and between 34% and 52% in five GLV. Multiple regression analysis revealed that these factors together accounted for 53% (r2 = 0.53) and 45% (r2 = 0.45) inhibition of iron and calcium absorption, respectively. These findings infer that calcium and iron availability is influenced by the constituents present in the GLV. Copyright © 2006 Society of Chemical Industry
Effect of ozone and calcium lactate treatments on browning and texture properties of fresh‐cut lettuce
Authors: Rico Daniel , Martín‐Diana Ana Belen , Frías Jesus M , Henehan Gary TM , Barry‐Ryan Catherine
Published: August 2006

The effects of three treatments, 1 mg L−1 ozone at 18–20 °C, 15 g L−1 calcium lactate (CLac) at 50 °C and a combination thereof, were compared on fresh‐cut lettuce over 10 days of refrigerated storage. Respiration rate, browning and texture were examined as main quality indicators. The use of ozone produced a significantly (P < 0.05) higher oxygen decline than the use of CLac (from day 3 to day 10). At the end of storage, CLac (alone or combined with ozone) samples had higher oxygen content (∼9%) than ozone samples (∼6%). Enzymatic activity decreased significantly (P < 0.05) in ozone samples. Polyphenol oxidase activity in fresh‐cut lettuce treated with ozone (alone or combined with CLac) showed lower values on day 1 (<2500 units g−1) and at the end of storage (<3000 units g−1) than CLac samples (4000–4800 units g−1). Ozone also reduced peroxidase activity to ∼300 units g−1 after treatment. Finally, pectin methylesterase activity was also reduced with ozone, showing a negative effect on textural properties. Data suggested that CLac maintained quality markers better than treatments with ozone and ozone/CLac combination over 10 days of storage. Copyright © 2006 Society of Chemical Industry
Sixty years of EHL
Authors: Spikes H. A.
Published: August 2006

It is now 60 years since Ertel produced the first solution to the elastohydrodynamic lubrication (EHL) problem. There has been enormous progress since then, both in numerical modelling and in experimental research on EHL. The moving, rough surface EHL problem can now be solved on laptop‐level computers, while maps of film thickness, pressure and temperature can be obtained experimentally from within rolling/sliding contacts. However, there remain some important questions that have not been fully resolved. One of the most contentious is how to describe the rheological properties of lubricants under the very severe conditions present in thin film EHL contacts. A second is how to model mixed lubricated contact, where the fluid film can break down at asperity conjunctions. But perhaps the greatest challenge to researchers in EHL is to produce useful design equations for predicting the performance of machine components operating in EHL and thereby ensure that EHL theory becomes an integral part of the design process. Copyright © 2006 John Wiley & Sons, Ltd.
New developments in natural products‐based anti‐AIDS research
Authors: Yu Donglei , Morris‐Natschke Susan L. , Lee Kuo‐Hsiung
Published: August 2006

This review discusses anti‐HIV natural products from several compound classes, including terpenoids, coumarins, alkaloids, polyphenols, tannins, and flavonoids. Natural products can provide novel anti‐AIDS chemotherapeutic leads that are structurally unique or have new mechanisms of action. The drug discovery and development process proceeds from bioactivity‐directed isolation and identification of a promising lead natural product, followed by rational design‐based structural modification and structure–activity relationship analyses to optimize the lead compound as a drug candidate. This process is notably exemplified by the discovery of the modified betulinic acid derivative, DSB [PA‐457], which is currently in Phase II clinical trial and is the first‐in‐class HIV maturation inhibitor (MI). © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 1, 108–132, 2007
MRI detects myocardial iron in the human heart
Authors: Ghugre Nilesh R. , Enriquez Cathleen M. , Gonzalez Ignacio , Nelson Marvin D. , Coates Thomas D. , Wood John C.
Published: August 2006

Iron‐induced cardiac dysfunction is a leading cause of death in transfusion‐dependent anemia. MRI relaxation rates R2(1/T2) and R(1/T) accurately predict liver iron concentration, but their ability to predict cardiac iron has been challenged by some investigators. Studies in animal models support similar R2 and R behavior with heart and liver iron, but human studies are lacking. To determine the relationship between MRI relaxivities and cardiac iron, regional variations in R2 and R were compared with iron distribution in one freshly deceased, unfixed, iron‐loaded heart. R2 and R were proportionally related to regional iron concentrations and highly concordant with one another within the interventricular septum. A comparison of postmortem and in vitro measurements supports the notion that cardiac R should be assessed in the septum rather than the whole heart. These data, along with measurements from controls, provide bounds on MRI‐iron calibration curves in human heart and further support the clinical use of cardiac MRI in iron‐overload syndromes. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
The significance of diabetes and disability: referrals made to a disability service
Authors: Singh R , Hunter J , Fulton C
Published: August 2006

Diabetes mellitus is an important cause of disability even after correction for complications. It has been suggested that diabetes may be underestimated in referrals to rehabilitation services. We tested this by assessing how often patients with diabetes had this diagnosis mentioned when referred to a wheelchair clinic. Two hundred consecutive referrals to a wheelchair service were assessed to ascertain whether diabetes was mentioned in the referral letter compared to how many actually had a diagnosis of diabetes. This was then compared to other medical conditions to assess whether diabetes was being under‐mentioned in referrals.

Only 7/29 (24.1%) patients with diabetes in the cohort had diabetes mentioned in their referral. By comparison, 34/42 (81%) of those with stroke/heart failure/chronic obstructive pulmonary disease were mentioned (χ2=22.69, df=1, p<0.001) There was no difference between those with diabetes mentioned or not mentioned in terms of age, gender, type of diabetes, HbA1c or complication rate.

We conclude that diabetes is under‐mentioned in referrals to a rehabilitation service. It may be the case that health services are yet to appreciate the significance of diabetes as a cause of disability compared to other major conditions that cause disability. There seems to be a need to create an awareness of the importance of diabetes in disability. Copyright © 2006 John Wiley & Sons, Ltd.
Diabetes and alcohol: time for realistic advice based on the evidence
Authors: Evans KM , Kerr D , Flanagan DE
Published: August 2006

The recommendation at present is that, if you have diabetes, alcohol should be avoided or restricted. It is clear that for a significant proportion of people with diabetes this advice is ignored. However, there is now much evidence to challenge the once accepted view that alcohol is best avoided by the patient with diabetes. Current epidemiological evidence would support the view that moderate alcohol consumption has health benefits particularly in reducing the risk of vascular disease. The difficulty is how we translate this knowledge into advice for people living with diabetes on a daily basis. This article considers the relationships between alcohol and diabetes: from weighing the epidemiological evidence, to practical clinical advice. Copyright © 2006 John Wiley & Sons, Ltd.