bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of malignancy in first‐degree relatives of patients with pancreatic carcinoma
Authors: McWilliams Robert R. , Rabe Kari G. , Olswold Curtis , De Andrade Mariza , Petersen Gloria M.
Published: May 2005

BACKGROUND

Approximately 5–10% of pancreatic carcinoma (PC) patients report a family history of the disease. In some families, mutations of tumor suppressor genes have been elucidated, but for most the causative gene remains unidentified. Counseling the families of PC patients regarding their risk of cancer remains problematic because little information is available.

METHODS

The authors analyzed family history questionnaires completed by 426 unselected, sequential Mayo Clinic patients with PC. The prevalence of malignancy reported among 3355 of their first‐degree relatives was compared with the Surveillance, Epidemiology, and End Results Project (SEER) 9 (2000) registry. Age‐adjusted and gender‐adjusted standardized incidence ratios (SIRs) were generated.

RESULTS

Greater than 130,000 person‐years at risk for cancer among the first‐degree relatives were analyzed. The risk of PC was found to be increased among the first‐degree relatives of patients with PC (SIR of 1.88; 95% confidence interval [95% CI], 1.27–2.68), as was the risk of liver carcinoma (SIR of 2.70; 95% CI, 1.51–4.46). Lymphoma (SIR of 0.28; 95% CI, 0.12–0.55), bladder carcinoma (SIR of 0.55; 95% CI, 0.31–0.89), breast carcinoma (SIR of 0.73; 95% CI, 0.57–0.92), lung carcinoma (SIR of 0.62; 95% CI, 0.47–0.80), and prostate carcinoma (SIR of 0.71; 95% CI, 0.54–0.92) were found to be underrepresented. When the proband was age < 60 years, the risk of PC to first‐degree relatives was found to be increased further (SIR of 2.86; 95% CI, 1.15–5.89). In this subgroup, no other malignancies were found to be significantly increased, although the risks of melanoma (SIR of 1.73; 95% CI, 0.70–3.57), ovarian carcinoma (SIR of 2.20; 95% CI, 0.72–5.12), and colon carcinoma (SIR of 1.37; 95% CI, 0.80–2.19) were suggestive.

CONCLUSIONS

There was a nearly twofold increased risk of PC in the first‐degree relatives of PC probands. This risk was found to increase nearly threefold when patients were diagnosed before age 60 years. At the current time, in the absence of a pedigree suggestive of known familial cancer syndromes, the current study results do not support targeted screening for other malignancies in the first‐degree relatives of patients with sporadic PC. Cancer 2005. © 2005 American Cancer Society.
Olfactory marker protein modulates primary olfactory axon overshooting in the olfactory bulb
Authors: St. John James A. , Key Brian
Published: May 2005

Olfactory marker protein (OMP) is expressed by mature primary olfactory sensory neurons during development and in adult mice. In mice that lack OMP, olfactory sensory neurons have perturbed electrophysiological activity, and the mice exhibit altered responses and behavior to odor stimulation. To date, defects in axon guidance in mice that lack OMP have not been investigated. During development of the olfactory system in mouse, primary olfactory axons often overshoot their target glomerular layer and project into the deeper external plexiform layer. These aberrant axonal projections are normally detected within the external plexiform layer up to postnatal day 12. We have examined the projections of primary olfactory axons in OMP‐tau:LacZ mice and OMP‐GFP mice, two independent lines in which the OMP coding region has been replaced by reporter molecules. We found that axons overshoot their target layer and grow into the external plexiform layer in these OMP null mice as they do in wild‐type animals. However, in the absence of OMP, overshooting axons are more persistent and remain prominent until 5 weeks postnatally, after which their numbers decrease. Overshooting axons are still present in these mice even at 8 months of age. In heterozygous mice, axons also overshoot into the external plexiform layer; however, there are fewer axons, and they project for shorter distances, compared with those in a homozygous environment. Our results suggest that perturbed electrophysiological responses, caused by loss of OMP in primary olfactory neurons, reduce the ability of primary olfactory axons to recognize their glomerular target. J. Comp. Neurol. 487:61–69, 2005. © 2005 Wiley‐Liss, Inc.
Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina
Authors: Hirano Arlene A. , Brandstätter Johann H. , Brecha Nicholas C.
Published: May 2005

The mechanism underlying transmitter release from retinal horizontal cells is poorly understood. We investigated the possibility of vesicular transmitter release from mammalian horizontal cells by examining the expression of synaptic proteins that participate in vesicular transmitter release at chemical synapses. Using immunocytochemistry, we evaluated the cellular and subcellular distribution of complexin I/II, syntaxin‐1, and synapsin I in rabbit retina. Strong labeling for complexin I/II, proteins that regulate a late step in vesicular transmitter release, was found in both synaptic layers of the retina, and in somata of A‐ and B‐type horizontal cells, of γ‐aminobutyric acid (GABA)‐ and glycinergic amacrine cells, and of ganglion cells. Immunoelectron microscopy demonstrated the presence of complexin I/II in horizontal cell processes postsynaptic to rod and cone ribbon synapses. Syntaxin‐1, a core protein of the soluble N‐ethylmaleimide‐sensitive‐factor attachment protein receptor (SNARE) complex known to bind to complexin, and synapsin I, a synaptic vesicle‐associated protein involved in the Ca2+‐dependent recruitment of synaptic vesicles for transmitter release, were also present in the horizontal cells and their processes at photoreceptor synapses. Photoreceptors and bipolar cells did not express any of these proteins at their axon terminals. The presence of complexin I/II, syntaxin‐1, and synapsin I in rabbit horizontal cell processes and tips suggests that a vesicular mechanism may underlie transmitter release from mammalian horizontal cells. J. Comp. Neurol. 488:70–81, 2005. Published 2005 Wiley‐Liss, Inc.
Functional circuits mediating sensorimotor integration: Quantitative comparisons of projections from rodent barrel cortex to primary motor cortex, neostriatum, superior colliculus, and the pons
Authors: Hoffer Zachary S. , Arantes Henry B. , Roth Richard L. , Alloway Kevin D.
Published: May 2005

Motor performance depends on somatosensory feedback, and consistent with this finding, primary somatosensory (SI) cortex projects to several regions involved in motor control. Although the pathways mediating sensorimotor integration are known, few studies have compared their projection patterns. Therefore, in each animal, we injected two anterograde tracers into SI barrel cortex and compared the relative density and spatial extent of the labeled projections to the primary motor (MI) cortex, neostriatum, superior colliculus, and basal pons. Quantitative analysis revealed that these projections terminated most extensively in the neostriatum, to a lesser extent in MI cortex, and innervated the least amount of neuropil in the superior colliculus and pontine nuclei. Tracer overlap in the pontine nuclei was significantly higher than in the other three brains regions, and was strongly correlated with overlap in the superior colliculus, presumably because some projections to these two brain regions represent collaterals of the same neurons. The density of labeled varicosities was highest in the pons and lowest in MI. As a proportion of total labeling, densely packed clusters of labeled terminals were most prevalent in the pons, less prevalent in neostriatum and superior colliculus, and least prevalent in MI cortex. These results are consistent with physiological evidence indicating strong coherence between SI barrel cortex and the cerebellum during whisking behavior. J. Comp. Neurol. 488:82–100, 2005. © 2005 Wiley‐Liss, Inc.
OPA1 expression in the normal rat retina and optic nerve
Authors: Ju Won‐Kyu , Misaka Takumi , Kushnareva Yulia , Nakagomi Saya , Agarwal Neeraj , Kubo Yoshihiro , Lipton Stuart A. , Bossy‐Wetzel Ella
Published: May 2005

Autosomal dominant optic atrophy (DOA) is the most common form of hereditary optic neuropathy. DOA presents in the first decade of life and manifests as progressive vision loss. In DOA retinal ganglion cells and the optic nerve degenerate by an unknown mechanism. The gene mutated in DOA, Optic Atrophy Type 1 (OPA1), encodes a dynamin‐related GTPase implicated in mitochondrial fusion and maintenance of the mitochondrial network and genome. Here, we determine which cell types in the normal retina and the optic nerve express OPA1. In the normal rat retina, OPA1 is expressed in the ganglion cell layer as well as in the outer plexiform layer, the inner nuclear layer, and the inner plexiform layer. In the ganglion cell layer, OPA1 is expressed predominantly in retinal ganglion cells. By contrast, OPA1 protein is low or undetectable in astrocytes and oligodendrocytes of the optic nerve. Additionally, OPA1 protein is present in axonal mitochondria. Last, OPA1 expression is present in mitochondria of processes and cell bodies of purified retinal ganglion cells and of the RGC‐5 cell line. Thus, OPA1 is predominantly expressed in retinal ganglion cells of the normal rat retina and axons of the optic nerve. These findings may explain the selective vulnerability of retinal ganglion cells to OPA1 loss of function. J. Comp. Neurol. 488:1–10, 2005. © 2005 Wiley‐Liss, Inc.
Disruption of synaptic development and ultrastructure by Drosophila NSF2 alleles
Authors: Stewart Bryan A. , Pearce Joanne , Bajec Martha , Khorana Radhika
Published: May 2005

First identified as the cytosolic component that restored intra‐Golgi vesicle trafficking following N‐ethylmaleimide poisoning, N‐ethylmaleimide‐sensitive factor (NSF) was later shown to be an ATPase that participates in many vesicular trafficking events. Current models hold that NSF disassembles postfusion SNARE protein complexes, allowing them to participate in further rounds of vesicle cycling. To further understand the role of NSF in neural function, we have embarked on genetic studies of Drosophila NSF2. In one approach, we employed transgenic flies that carry a dominant‐negative form of NSF2 (NSFE/Q). When expressed in neurons this construct suppresses synaptic transmission, increases activity‐dependent fatigue of transmitter release, and reduces the functional size of the pool of vesicles available for release. Unexpectedly, it also induced pronounced overgrowth of the neuromuscular junction. The aim of the present study was twofold. First, we sought to determine if the neuromuscular junction (NMJ) overgrowth phenotype is present throughout development. Second, we examined NSF2E/Q larval synapses by serial section electron microscopy in order to determine if there are ultrastructural correlates to the observed physiological and morphological phenotypes. We indeed found that the NMJ overgrowth phenotype is present at the embryonic neuromuscular synapse. Likewise, at the ultrastructural level, we found considerable alterations in the number and distribution of synapses and active zones, whereas the number of vesicles present was not changed. From these data we conclude that a primary phenotype of the NSF2E/Q transgene is a developmental one and that alteration in the number and distribution of active zones contributes to the NSF2E/Q physiological phenotype. J. Comp. Neurol. 487:101–111, 2005. © 2005 Wiley‐Liss, Inc.
Neurotransmitter phenotypes of intermediate zone reticular formation projections to the motor trigeminal and hypoglossal nuclei in the rat
Authors: Travers Joseph B. , Yoo Ji‐Eun , Chandran Ravi , Herman Kenneth , Travers Susan P.
Published: May 2005

Numerous studies suggest an essential role for the intermediate (IRt) and parvocellular (PCRt) reticular formation (RF) in consummatory ingestive responses. Although the IRt and PCRt contain a large proportion of neurons with projections to the oromotor nuclei, these areas of the RF are heterogeneous with respect to neurotransmitter phenotypes. Glutamatergic, GABAergic, cholinergic, and nitrergic neurons are all found in the PCRt and IRt, but the projections of neurons with these phenotypes to the motor trigeminal (mV) and hypoglossal nucleus (mXII) has not been fully evaluated. In the present study, after small injections of Fluorogold (FG) into mV and mXII, sections were processed immunohistochemically to detect retrogradely labeled FG neurons in combination with the synthetic enzymes for nitric oxide (nitric oxide synthase) or acetylcholine (choline acetyltransferase) or in situ hybridization for the synthetic enzyme for GABA (GAD65/67) or the brainstem vesicular transporter for glutamate (VGLUT2). In three additional cases, FG injections were made into one motor nucleus and cholera toxin (subunit b) injected in the other to determine the presence of dual projection neurons. Premotor neurons to mXII (pre‐mXII) were highly concentrated in the IRt. In contrast, there were nearly equal proportions of premotor‐trigeminal neurons (pre‐mV) in the IRt and PCRt. A high proportion of pre‐oromotor neurons were positive for VGLUT2 (pre‐mXII: 68%; pre‐mV: 53%) but GABAergic projections were differentially distributed with a greater projection to mV (25%) compared to mXII (8%). Significant populations of cholinergic and nitrergic neurons overlapped pre‐oromotor neurons, but there was sparse double‐labeling (<10%). The IRt also contained a high proportion of neurons that projected to both mV and MXII. These different classes of premotor neurons in the IRt and PCRt provide a substrate for the rhythmic activation of lingual and masticatory muscles. J. Comp. Neurol. 487:28–47, 2005. © 2005 Wiley‐Liss, Inc.
Estimating cell death in G2M using bivariate BrdUrd/DNA flow cytometry
Authors: White R. Allen , Asmuth David M. , Lu Ying , Wang Nan , Li Xiao‐Dong , Reece Lisa , Pollard Richard B. , Nokta Mostafa , Leary James F. , Terry Nicholas H. A.
Published: May 2005

Background

In an accompanying paper (Asmuth et al.) it was found necessary to include cell death explicitly to estimate parameters of cell proliferation. The use of bivariate flow cytometry to estimate the phase durations and the doubling times of cells labeled with thymidine analogues is well established. However, these methods of analysis do not consider the possibility of cell death. This report demonstrates that estimating cell death in G2/M is possible.

Methods

Mathematical models for the experimental quantities, the fraction of labeled undivided cells, the fraction of labeled divided cells, and the relative movement were developed. These models include the possibility that, of the cells with G2/M DNA content, only a certain fraction will divide, with the remainder dying after some time TR. Simulation studies were conducted to test the possibility of using simple methods to estimate phase durations and cell death rates.

Results

Cell death alters the estimates of phase transit times in a rather complex manner that depends on the lifetime of the doomed cells. However, it is still possible to obtain estimates of the phase durations of cells in S and G2/M and the death rates of cells in G2/M.

Conclusions

The methods presented herein provide a new way to characterize cell populations that includes cell death rates and common measurements of cell proliferation. © 2005 Wiley‐Liss, Inc.
Novel fluorescence assay using calcein‐AM for the determination of human erythrocyte viability and aging
Authors: Bratosin Daniela , Mitrofan Laura , Palii Carmen , Estaquier Jérôme , Montreuil Jean
Published: May 2005

Background

A highly sensitive, fast, and simple flow cytometric assay to assess human red blood cell (RBCs) viability and aging is reported.

Methods

The assay described in this report is based on the use of acetoxymethyl ester of calcein (calcein‐AM), a fluorescein derivative and nonfluorescent vital dye that passively crosses the cell membrane of viable cells and is converted by cytosolic esterases into green fluorescent calcein, which is retained by cells with intact membranes and inactive multidrug resistance protein. The loss of calcein can be easily determined by flow cytometry, and the cytosolic localization of esterases was demonstrated by spectrofluorometric analyses.

Results

We found that RBCs incubated with Ca2+, which induces a rapid and modulated self‐death that shares several features with apoptosis (Bratosin et al., Cell Death Differ 2001;8:1143–1156), externalized phosphatidylserine and lost calcein staining and cytosolic adenosine triphosphate content. Double labeling using phycoerythrin‐labeled annexin‐V and calcein‐AM showed that the decrease of esterase activity is an early event that precedes the externalization of phosphatidylserine residues. In addition, this assay allowed us to distinguish young and aged RBCs isolated by ultracentrifugation in a self‐forming Percoll gradient and can be considered as a reliable marker of RBC aging.

Conclusions

Calcein‐AM assay may represent a wide application for assessing RBC viability, particularly in blood banks. © 2005 Wiley‐Liss, Inc.
Segmentation of complex cell clusters in microscopic images: Application to bone marrow samples
Authors: Nilsson Björn , Heyden Anders
Published: May 2005

Background

Morphologic examination of bone marrow and peripheral blood samples continues to be the cornerstone in diagnostic hematology. In recent years, interest in automatic leukocyte classification using image analysis has increased rapidly. Such systems collect a series of images in which each cell must be segmented accurately to be classified correctly. Although segmentation algorithms have been developed for sparse cells in peripheral blood, the problem of segmenting the complex cell clusters characterizing bone marrow images is harder and has not been addressed previously.

Methods

We present a novel algorithm for segmenting clusters of any number of densely packed cells. The algorithm first oversegments the image into cell subparts. These parts are then assembled into complete cells by solving a combinatorial optimization problem in an efficient way.

Results

Our experimental results show that the algorithm succeeds in correctly segmenting densely clustered leukocytes in bone marrow images.

Conclusions

The presented algorithm enables image analysis–based analysis of bone marrow samples for the first time and may also be adopted for other digital cytometric applications where separation of complex cell clusters is required. © 2005 Wiley‐Liss, Inc.
C–H vs. N–H Bond Activation in Aminophosphane Ligands: Reaction of [Cp*Ru(MeCN)2(PR12NHR2)]+ (R1 = Ph, iPr; R2 = Ph, C6F5) with Alkynes
Authors: Jiménez‐Tenorio Manuel , Puerta M. Carmen , Valerga Pedro
Published: May 2005

The reaction of the complexes [Cp*Ru(MeCN)2(PR12NHR2)]+ (R1 = R2 = Ph 1; R1 = iPr, R2 = C6F5 2; R1 = iPr, R2 = Ph 3) with 1‐alkynes HC≡CR (R = H, nBu, SiMe3) or diynes HC≡CCH2XCH2C≡CH (X = O, CH2, CH2CH2) yields different products depending on the nature of the aminophosphane ligand. In some cases, alkyne coupling involving migration of the phosphane and N–H activation occurs, yielding amidobutadiene complexes of the type [Cp*Ru{η4‐C4H3(R)2PR12NR2‐κ1N}]+ or [Cp*Ru{η4‐C4H3(CH2XCH2)PR12NR2‐κ1N}]+. The complexes [Cp*Ru{η4‐C4H3(CH2OCH2)PPh2NPh‐κ1N}][PF6] (1a) and [Cp*Ru{η4‐C4H3(CH2OCH2)PiPr2NC6F5‐κ1N}][PF6] (2a) have been structurally characterized by X‐ray crystallography. In other cases, for example the reaction of 3 with HC≡CR (R = nBu, SiMe3), C–H bond activation at the ortho‐position of the phenyl ring of the phenylamino moiety and coupling to the alkyne fragment takes place. This results in the formation of the novel π‐alkene complexes [Cp*Ru(MeCN){η2‐RCH=CH(C6H4)NHPiPr2‐κ1P}]+ (R = nBu 4, SiMe3 5), formally derived from the insertion of the alkyne into the ortho‐C–H bond of the phenyl ring. The derivative [Cp*Ru(MeCN){η2‐nBuCH=CH(C6H4)NHPiPr2‐κ1P}][BPh4] has been structurally characterized by X‐ray crystallography. These compounds are related to the also structurally characterized olefin complex [Cp*Ru(MeCN)(η2‐MeOOCCH=CH2)(PPh2NHPh)][PF6] (6), generated by reaction of 1 with methyl acrylate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and X‐ray Molecular Structure of (PNP)2[MoIV(C6H4S2‐1,2)3] Completing the Structural Characterization of the Series [Mo(C6H4S2‐1,2)3]n– (n = 0, 1, 2)
Authors: Schulze Isfort Christian , Pape Tania , Hahn F. Ekkehardt
Published: May 2005

The tris(benzene‐1,2‐dithiolato) complex (Li)2[MoIV(C6H4S2‐1,2)3] {(Li)2[MoIV(bdt)3]} (bdt2– = C6H4S2‐1,2 dianion) was synthesized from [MoCl4(CH3CN)2], (H2bdt), and nBuLi in THF. Complex (Li)2[MoIV(bdt)3] undergoes aerial oxidation to give Li[MoV(bdt)3]. Both complexes were crystallized from methanol as the salts (PNP)2[MoIV(bdt)3] and (PNP)[MoV(bdt)3] {PNP+ = bis(triphenylphosphoranylidene)ammonium cation}, and their molecular structures were determined by X‐ray diffraction. The molybdenum(IV) complex [MoIV(bdt)3]2– assumes a distorted trigonal prismatic coordination geometry (average twist angle= 24.8°) while the coordination geometry of [MoV(bdt)3]– is best described as distorted octahedral (average twist angle= 34.1°). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Binuclear Copper(II) Complex Containing the Pyrazine‐2,5‐dicarboxylate Ligand: Study of the Magnetic Exchange through the Pyrazine Bridge
Authors: Beobide Garikoitz , Castillo Oscar , García‐Couceiro Urko , García‐Terán Juan P. , Luque Antonio , Martínez‐Ripoll Martín , Román Pascual
Published: May 2005

The compound [Cu2(μ‐pzdc)(phen)4](NO3)2·10H2O (1; pzdc = pyrazine‐2,5‐dicarboxylato; phen = 1,10‐phenanthroline) has been structurally and magnetically characterised. Theoretical calculations have allowed us to establish a plausible magneto‐structural correlation for pyrazine‐bridged complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Diastereoselective Lewis Acid Mediated Reductions of α‐Alkyl‐β‐Functionalized Carbonyl Compounds
Authors: Bartoli Giuseppe , Bartolacci Massimo , Giuliani Arianna , Marcantoni Enrico , Massaccesi Massimo
Published: May 2005

A high stereochemical induction has often been observed in the reduction of ketones with stereogenic centres close to the carbonyl function. The level of stereoselectivity is particularly high when “hard” donor groups such as nitrogen or oxygen atoms are present in the molecule. These results have been commonly explained in terms of a chelate‐controlled process. However, this interpretation has recently been challenged, and in many cases an open‐chain mechanism can better account for the observed results. Thus, Lewis‐acid‐mediated chelation and nonchelation control is one of the most fundamental and practical concepts in transferring a nucleophile moiety to carbonyl compounds. In order to clarify the role of a hard Lewis acid in controlling the stereochemical outcome of a given reaction, the Lewis acid mediated reduction of a series of α‐alkyl‐β‐functionalized carbonyl compounds with metallic hydrides in various solvents was recently investigated. In particular, the results derived from the reductions in the presence of dry CeCl3were compared to those obtained under the same experimental conditions but in the presence of TiCl4, whose ability to form chelation complexes is well established. These investigations show a stereochemical outcome that is fully consistent with a chelation‐controlled pathway in the case of titanium, and an open‐chain‐controlled pathway in the case of CeCl3. The strongly chelating TiCl4led to thesynisomer in high diastereomeric excess in noncoordinating solvents at –78 °C with borane–Lewis base complex reducing agents, while nonchelating CeCl3produced a high excess of theantiisomer in coordinating solvents at the same temperature with metal borohydrides as reducing agent. Therefore, our method based on the choice of CeCl3or TiCl4as a Lewis acid under the reported conditions represents a significant contribution to the development of new stereoselective reductions of α‐alkyl‐β‐functionalized ketones. These procedures are one of the best known ways to obtain an alcoholic moiety. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Iridium(I)‐Catalysed Tandem Hydrosilylation‐Protodesilylation of Imines
Authors: Field Leslie D. , Messerle Barbara A. , Rumble Sarah L.
Published: May 2005

In the presence of alkylsilanes, the cationic IrI complex [{Ir[bis(pyrazol‐1‐yl)methane](CO)2}BPh4] (1) catalyses the reduction of a range of imines, including N‐alkyl and N‐aryl imines, and both aldimines and ketimines. Excellent conversions directly to the product amines are achieved rapidly at room temperature in methanol solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Proton‐Conducting Polymer Electrolyte Membranes Based on Fluoropolymers Incorporating Perfluorovinyl Ether Sulfonic Acids and Fluoroalkenes: Synthesis and Characterization
Authors: Souzy R. , Ameduri B. , Boutevin B. , Capron P. , Marsacq D. , Gebel G.
Published: May 2005

This paper presents the synthesis of new polymer electrolyte membranes based on fluoropolymers incorporating aromatic perfluorovinyl ether sulfonic acids. A novel synthetic route describing the preparation of perfluorovinyl ether monomer containing sulfonic functionalities, 4‐[(α,β,β‐trifluorovinyl)‐oxy]benzene sulfonic acid (TFVOBSA), is reported. The radical (co) and terpolymerisation of 4‐[(α,β,β‐trifluorovinyl)oxy]benzene sulfonyl chloride (TFVOBSC) with 1,1‐difluoroethylene (or vinylidene fluoride, VDF), hexafluoropropene (HFP), and perfluoromethyl vinyl ether (PMVE) is described. The terpolymers of TFVOBSC with VDF and HFP, or VDF and PMVE, were hydrolysed and also led to new fluorinated terpolymers bearing sulfonic acid aromatic side‐groups. The terpolymers were characterized by 1H and 19F NMR spectroscopies, SEC, DSC, and TGA. Membranes incorporating these functional fluoropolymers were prepared and the electrochemical properties (IEC, proton conductivity, swelling rates) were studied and discussed.
Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: An mFISH study
Authors: Hande M. Prakash , Azizova Tamara V. , Burak Ludmilla E. , Khokhryakov Valentin F. , Geard Charles R. , Brenner David J.
Published: May 2005

Long‐lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24‐color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear‐weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral‐blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long‐lived, quantitative, low‐background biomarker of densely ionizing radiation for human populations exposed many years ago. © 2005 Wiley‐Liss, Inc.
Early evening low alcohol intake also worsens sleepiness‐related driving impairment
Authors: Barrett Pauline R. , Horne James A. , Reyner Louise A.
Published: May 2005

Following night‐time sleep restriction, afternoon driving performance during the bi‐circadian surge in afternoon sleepiness is markedly worsened by blood alcohol concentrations (BACs) well under most national driving limits. This study assessed how driving with this same sleep restriction and BACs (av 40 mg and 28 mg alcohol/100 ml blood at the beginning and end of drive, respectively) respond during the evening circadian rise in alertness. In a 2 × 2 (alcohol versus control drink [double blind] × normal night sleep versus sleep restricted), repeated‐measures design, eight healthy young men drove for 2 h from 18:00 h, in a real‐car simulator, on a monotonous, simulated highway. Driving impairment (lane drifting), subjective sleepiness and EEG measures of sleepiness were recorded. While sleep restriction alone produced significant impairments to evening driving and subjective sleepiness, alcohol alone did not. However, alcohol combined with sleep restriction significantly worsened all indices, although, this was less than that found for afternoon driving with identical interventions. Whereas low BACs may not affect driving in normally alert drivers in the early evening, the addition of moderate sleep restriction still produces a dangerous combination. Probably, there is no ‘safe’ level of alcohol intake for otherwise sleepy drivers, at any time of the day. Copyright © 2005 John Wiley & Sons, Ltd.
Involvement of the NMDA receptor, NO‐cyclic GMP and nuclear factor K‐β in an animal model of repeated trauma
Authors: Harvey Brian H. , Bothma Tanya , Nel Ané , Wegener Gregers , Stein Dan J.
Published: May 2005

Post‐traumatic stress disorder (PTSD) may be associated with shrinkage of the hippocampus, with glutamate release causally related to these events. Recent animal studies strongly implicate activation of the nitric oxide (NO)‐cascade in anxiety and stress. Using an animal model of repeated trauma, the effect of stress was investigated on the hippocampal NO‐cGMP signalling pathway, specifically the release of nitrogen oxides (NOx) and its modulation by NMDA receptor‐, NO‐, cGMP‐ and nuclear factor K‐β (NFK‐β)‐selective drugs. Immediately after stress, rats received the glutamate NMDA receptor antagonist, memantine (MEM; 5 mg/kg i.p./d), the NO synthase inhibitor, 7‐nitroindazole sodium salt (7‐NINA; 20 mg/kg i.p./d), the cGMP‐specific PDE inhibitor, sildenafil (SIL; 10 mg/kg i.p./d) or the NFκ‐β antagonist, pyrollidine dithiocarbamate (PDTC; 70 mg/kg i.p./d), for 7 days. Stress significantly increased hippocampal NOx on day 7 post‐stress, which was blocked by either 7‐NINA or PDTC, while MEM was without effect. SIL, however, significantly augmented stress‐induced NOx accumulation. Increased cGMP therefore acts as a protagonist in driving stress‐related events, while both nNOS (neuronal NOS) and iNOS (inducible/immunological NOS) may represent a therapeutic target in preventing the effects of severe stress. The value of NMDA receptor antagonism, however, appears limited in this model. Copyright © 2005 John Wiley & Sons, Ltd.
HA/TCP compounding of a porous CaP biomaterial improves bone formation and scaffold degradation—A long‐term histological study
Authors: Schopper Christian , Ziya‐Ghazvini Farzad , Goriwoda Walter , Moser Doris , Wanschitz Felix , Spassova Else , Lagogiannis Georgios , Auterith Alexandra , Ewers Rolf
Published: May 2005

In the present study, two biphasic calcium phosphate biomaterials (BCP) with HA/TCP ratios of 50/50 and 30/70 were obtained from a pure HA biomaterial. The biomaterials which showed the same three‐dimensional geometry were implanted into corticocancellous costal defects of sheep. In the specimens of all three biomaterials, abundant bone formation, mineral dissolution from the biomaterial scaffolds, and active cellular resorption of the scaffolds was present after 6 and 12 months. Backscattered electron microscopy showed bone invasion into the pores of the scaffolds and micromechanical interlocking at the bone/biomaterial interface without intervening soft tissue. The pattern of bone formation and scaffold resorption was different for cortical and cancellous bone. No time‐based effect, however, was observed. Overall, the BCP biomaterials had formed significantly more bone than the HA biomaterial. Also, scaffold resorption, which was followed by a replacement with newly formed bone, was significantly higher in the BCP biomaterials. Although no significant differences were observed between both BCP biomaterials, the present study had confirmed the assumption that HA/TCP compounding was suitable to improve bone formation and scaffold resorption in the investigated biomaterials and at the same time maintain the osteoconductive properties of the scaffolds. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Nowhere‐zero 3‐flows in products of graphs
Authors: Shu Jinlong , Zhang Cun‐Quan
Published: May 2005

A graph G is an odd‐circuit tree if every block of G is an odd length circuit. It is proved in this paper that the product of every pair of graphs G and H admits a nowhere‐zero 3‐flow unless G is an odd‐circuit tree and H has a bridge. This theorem is a partial result to the Tutte's 3‐flow conjecture and generalizes a result by Imrich and Skrekovski [7] that the product of two bipartite graphs admits a nowhere‐zero 3‐flow. A byproduct of this theorem is that every bridgeless Cayley graph G = Cay(Γ,S) on an abelian group Γ with a minimal generating set S admits a nowhere‐zero 3‐flow except for odd prisms. © 2005 Wiley Periodicals, Inc. J Graph Theory
Intraoperative Direct Measurement of Hepatic Arterial Buffer Response in Patients With Or Without Cirrhosis
Authors: Aoki Taku , Imamura Hiroshi , Kaneko Junichi , Sakamoto Yoshihiro , Matsuyama Yutaka , Kokudo Norihiro , Sugawara Yasuhiko , Makuuchi Masatoshi
Published: May 2005

The hepatic arterial buffer response (HABR) is an intrinsic regulatory mechanism of the hepatic artery (HA) that compensates for reductions in portal venous (PV) blood flow. Whether this response is maintained in patients with cirrhosis (LC) is unclear. The aim of the present study was to examine whether HABR is maintained in patients with LC using direct blood flow measurements. PV and HA blood flow were intraoperatively measured and compared in patients with (LC group, n = 39) or without (control group, n = 22) cirrhosis at baseline (baseline HABR) and after PV clamping (acute HABR) using an ultrasound transit-time flowmeter. In contrast to the proportional relationship between the baseline PV and HA blood flow observed in the control group, HA blood flow and the HA-PV flow ratio increased when PV blood flow decreased in the LC group, suggesting that the baseline HABR had already been activated. Acute HABR, evaluated by the absolute and relative changes in HA blood flow and by the buffer capacity, was blunted in the LC group (

P

< 0.001,

P

< 0.01, and

P

= 0.01, respectively). An association between the degree of acute HABR impairment and the level of baseline HABR activation (HA-PV flow ratio) could not be confirmed in the LC group. In conclusion, the baseline HABR appears to be continuously activated in patients with LC; this phenomenon probably results in the impairment of the acute HABR.
Air Transportation of Patients With End-Stage Liver Disease to Distant Liver Transplantation Centers
Authors: Shibolet Oren , Rowe Mina , Safadi Rifaat , Levy Izhar , Zamir Gideon , Eid Ahmed , Donchin Yoel , Ilan Yaron , Shouval Daniel
Published: May 2005

The Israeli population does not meet its transplantation organ needs. Therefore, liver transplantation (LTX) candidates are sometimes transported to centers abroad. We aimed to assess the demographic and clinical issues concerning this policy. Records of all candidates transported (2000–2004) were retrospectively reviewed. Data included etiology, disease severity, outcome, distances traveled and destinations, and medical complication arising en route. Forty-three candidates were transported overseas: 12 patients with fulminant hepatic failure (FHF) and 31 with cirrhosis. Average MELD score was 19.94, and the APACHE II score for patients with FHF was 20.5. Destinations included the United States, Colombia, Belgium, Germany, China, and Italy. Average distance traveled was 4,660 miles. Two patients were intubated and sedated during flight. All patients safely reached their destinations: 8 died prior to transplantation, 5 died after transplantation, 3 are awaiting transplantation, 3 recovered spontaneously, and the rest successfully underwent transplantation and returned home. In conclusion, our results suggest that long-distance transportation of patients awaiting liver transplantation is safe and technically feasible provided precaution measures are taken. Therefore, allocation regions may be broadened to include larger and more distant populations.
Who Among Cytomegalovirus-Seropositive Liver Transplant Recipients Is at Risk for Cytomegalovirus Infection?
Authors: Singh Nina , Wannstedt Cheryl , Keyes Lois , Wagener Marilyn M. , Cacciarelli Thomas V.
Published: May 2005

A vast majority of the transplant recipients are cytomegalovirus (CMV)-seropositive (R+). We sought to assess variables predictive of CMV infection, specifically in R+ liver transplant recipients. Study patients comprised 182 consecutive liver transplant recipients who survived at least 14 days after transplantation. Surveillance testing was used to detect CMV infection. Pre-emptive therapy was employed for the prevention of CMV disease, however, no antiviral prophylaxis was used for CMV infection. CMV infection developed in 32.5% (38 of 117) of R+ patients, 84.6% (33 of 39) of R−/D+, and 3.8% (1 of 26) of R−/D− patients. In R+ patients, Hispanic race (21.6% vs. 7.8%,

P

= 0.06), donor CMV seropositivity (73.7% vs. 45.6%,

P

= 0.005), and hepatocellular carcinoma (23.7% vs. 6.3%,

P

= 0.05) correlated with a higher risk of CMV infection. In a multivariate model, Hispanic race (OR: 3.5, 95% CI: 1.03-11.6,

P

= 0.045), donor CMV serostatus (OR: 4.0, 95% CI: 1.6-10.2,

P

= 0.003) and hepatocellular carcinoma (OR: 5.8, 95% CI: 1.6-20.5,

P

= 0.006) were all significant independent predictors of CMV infection. The aforementioned variables did not portend a higher risk of CMV infection in R−/D+ patients; donor CMV seropositivity overwhelmed all other risk factors in R− patients (

P

< 0.00001). In conclusion, CMV-seropositive liver transplant recipients at risk for CMV infection can be identified based on readily assessable variables. Preventive strategies may be selectively targeted toward these patients.
Induction of Umbilical Cord Blood–Derived β2m−c-Met+ Cells Into Hepatocyte-Like Cells by Coculture With CFSC/HGF Cells
Authors: Wang Yunfang , Nan Xue , Li Yanhua , Zhang Rui , Yue Wen , Yan Fang , Pei Xuetao
Published: May 2005

Several studies have indicated that adult stem cells derived from bone marrow (BM) and cord blood (CB) can differentiate into hepatocyte-like cells. This ability is important for the treatment of hepatic diseases with BM or CB as a potential approach. However, methods are still being developed for the efficient induction of stem cell differentiation and expansion to get enough cells to be useful. In the present study, we enriched a subset of umbilical cord blood β2m−c-Met+ cells (UCBCCs) and investigated the combination effect of liver nonparenchymal cells (cirrhotic fat-storing cells [CFSCs]) and hepatocyte growth factor (HGF) on the induction of UCBCCs into hepatocyte-like cells. UCBCCs were cocultured with CFSC/HGF feeder layers either directly or separately using insert wells. Flow cytometric analysis showed that most UCBCCs were CD34+/−CD90+/−CD49f+CD29+Alb+AFP+. After cocultured with transgenic feeder layers for 7 days, UCBCCs displayed some morphologic characteristics of hepatocytes. Reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence cell staining proved that the induced UCBCCs expressed several hepatocyte specific genes including AFP, Alb, CYP1B1 and cytokeratins CK18 and CK19. Furthermore, the induced cells displayed liver specific functions of indocyanine green (ICG) uptake, ammonium metabolism and albumin secretion. Hence, our data have demonstrated that UCBCCs might represent a novel subpopulation of CB-derived stem/progenitor cells capable of successful differentiation into hepatocyte-like cells when incubated with CFSC/HGF cells. In conclusion, not only HGF but also CFSCs and/or the secreted extracellular matrix (ECM) have been shown to be able to serve as essential microenvironment for hepatocyte differentiation.
Early Detection of Acute Renal Failure by Serum Cystatin C: a New Opportunity for a Hepatologist
Authors: Mazur Marek J. , Heilman Raymond L.
Published: May 2005

Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by >/= 50% (R-criteria), by >/= 100% (I-criteria), or by >/= 200% (F-criteria). In analogy, ARF was detected when cystatin C increased by >/= 50%, by >/= 100%, or by >/= 200%. Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by >/= 50% 1.5 +/− 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T(3)- or T(3)/T(4) syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine. (Kidney Int 2004;66:1115-1122)
Cryopreserved Iliac Artery Is Indispensable Interposition Graft Material for Middle Hepatic Vein Reconstruction of Right Liver Grafts
Authors: Hwang Shin , Lee Sung-Gyu , Ahn Chul-Soo , Park Kwang-Min , Kim Ki-Hun , Moon Deok-Bog , Ha Tae-Yong
Published: May 2005

Cryopreserved iliac vein grafts (IVGs) have often been used for reconstruction of middle hepatic vein (MHV) branches in right liver grafts, but their storage pool has often been exhausted in our institution due to the low incidence of deceased donor organ procurement. To overcome this shortage of IVG, we started to use cryopreserved iliac artery graft (IAG). During September and October 2004, we carried out 41 cases of adult living donor liver transplantation, including 29 right lobe grafts with MHV reconstruction. Interposition vessel grafts were autologous vein (n = 6), IVG (n = 13), and IAG (n = 10). IAG was used in 3 (21%) of 13 cases during the first month. For the next month, it was more frequently used (7 [44%] of 16) because handling of cryopreserved IAG was not difficult and its outcome was favorable. On follow-up with computed tomography for 3 months, outflow disturbance occurred in 1 (17%) of 6 autologous vein cases, in 2 (15%) of 13 IVG cases, and in 1 (10%) of 10 IAG cases. Two-month patency rate of IAG was not lower than that of IVG. In conclusion, we feel that cryopreserved IAG can be used as an interposition vessel graft for MHV reconstruction of right liver graft when cryopreserved IVG is not available.
New-Onset Diabetes After Liver Transplantation: From Pathogenesis to Management
Authors: Marchetti Piero
Published: May 2005

New-onset diabetes mellitus (NODM) develops in approximately 15% of liver transplant recipients, and a similar proportion of patients have diabetes prior to transplantation. Preexisting diabetes and probably NODM are associated with increased mortality and risk of infection. NODM occurs more frequently among patients with hepatitis C infection; additional risk factors include family history, male gender, increasing weight, and alcoholic cirrhosis. Corticosteroid therapy, particularly bolus injections, increases likelihood of NODM, and randomized clinical trials and retrospective studies have shown NODM to occur more frequently with tacrolimus compared with cyclosporine. Patients undergoing liver transplantation should be screened for diabetes risk factors, and fasting plasma glucose should be monitored regularly in all transplant recipients. Management of NODM is essentially similar to that of diabetes in the nontransplant population, and includes dietary and lifestyle modifications. In choosing oral agents and/or insulin, the individual medical profile of the patient must be considered carefully. Corticosteroid exposure should be limited as much as possible, and reduction of calcineurin inhibitor dose is prudent. Switching from tacrolimus to cyclosporine may be required in some cases to achieve improvement or resolution. In conclusion, prospective trials are necessary to properly define antidiabetic therapy and immunosuppressive strategies in this population.
Transmission of An Undiagnosed Sarcoma to Recipients of Kidney and Liver Grafts Procured in a Non-Heart Beating Donor
Authors: Detry Olivier , De Roover Arnaud , de Leval Laurence , Herens Christian , Delwaide Jean , Honoré Pierre , Meurisse Michel
Published: May 2005

Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a Maastricht category 3 non-heart beating donor. To the authors' knowledge this case is the first report of such a transmission with a liver graft procured in a non-heart beating donor. The cancer transferal was diagnosed 1 year after transplantation in the recipients of the liver and of one kidney. The liver recipient died from multiple organ failure after a failed attempt of tumor resection. The kidney recipient underwent immunosuppression withdrawal and transplantectomy. Non-heart beating donors should not be particularly at risk for undiagnosed cancer transmission if the procurement is performed according to the same rules of careful inspection of the abdominal and thoracic organs. After diagnosis of donor cancer transmission, kidney recipients should have the graft removed, and immunosuppression should be interrupted. The management of liver graft recipients is very difficult in this setting, and long-term survival was very rarely reported.