bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes That Control Ray Sensory Neuron Axon Development in the Caenorhabditis elegans Male
Authors: Jia Lingyun , Emmons Scott W
Published: April 2006

We have studied how a set of male-specific sensory neurons in Caenorhabditis elegans establish axonal connections during postembryonic development. In the adult male, 9 bilateral pairs of ray sensory neurons innervate an acellular fan that serves as a presumptive tactile and olfactory organ during copulation. We visualized ray axon commissures with a ray neuron-specific reporter gene and studied both known and new mutations that affect the establishment of connections to the pre-anal ganglion. We found that the UNC-6/netrin-UNC-40/DCC pathway provides the primary dorsoventral guidance cue to ray axon growth cones. Some axon growth cones also respond to an anteroposterior cue, following a segmented pathway, and most or all also have a tendency to fasciculate. Two newly identified genes, rax-1 and rax-4, are highly specific to the ray neurons and appear to be required for ray axon growth cones to respond to the dorsoventral cue. Among other genes we identified, rax-2 and rax-3 affect anteroposterior signaling or fate specification and rax-5 and rax-6 affect ray identities. We identified a mutation in sax-2 and show that the sax-2/Furry and sax-1/Tricornered pathway affects ectopic neurite outgrowth and establishment of normal axon synapses. Finally, we identified mutations in genes for muscle proteins that affect axon pathways by distorting the conformation of the body wall. Thus ray axon pathfinding relies on a variety of general and more ray neuron-specific genes and provides a potentially fruitful system for further studies of how migrating axon growth cones locate their targets. This system is applicable to the study of mechanisms underlying topographic mapping of sensory neurons into target circuitry where the next stage of information processing is carried out.
Density Changes around Phosphorus Granules and Fluid Bands in a Calcareous Soil
Authors: Hettiarachchi Ganga M. , Lombi Enzo , McLaughlin Mike J. , Chittleborough David , Self Peter
Published: April 2006

We employed x‐ray computed microtomography (X‐ray CT) to observe differences in moisture around fertilizer P granules (monoammonium phosphate, MAP) versus injection zones of fluid P fertilizer (technical grade monoammonium phosphate, TG MAP) in a calcareous soil over time. X‐ray CT allows nondestructive visualization of small columns containing soils and fertilizers. We were able to visualize the increase in density around the highly hygroscopic fertilizer granule over time. It appeared that both water flow toward the granule and precipitation of P could be responsible for the development of about 1 mm thick high density zone immediately adjacent to the granule. The mass flow of water toward the granule may have slowed or restricted the diffusion of fertilizer P from the granule, thus increasing the chances for P fixation through precipitation reactions. Also, the granule became less dense with time indicating the progress of granule dissolution. In contrast, injection of fluid fertilizer (TG‐MAP) in soil did not result in moisture changes over time as evidenced by a lack of X‐ray CT detectable density differences in the soil column. These data support previous findings that, when P is supplied in granular form, P diffusion and isotopic lability in calcareous soils are reduced compared with equivalent liquid fertilizer formulations, probably due to precipitation reactions induced by osmotically induced flow of soil moisture into the fertilizer granule.
Gregory Nazianzen in the Service of Humanist Social Reform
Authors: Davis Natalie Zemon
Published: April 2006

In 1539 Sébastien Gryphius, noted humanist printer of Lyon, published a French translation of Sermon Fourteen of Gregory Nazianzen, περί ϕιƛοπτωχίαs or De amore pauperum. It was entitled De la cure, et nourrissement des Pauvres, Sermon du Benoist sainct Gregoire Nazanzene, surnommé par excellence Theologien and it was the first of Gregory's works to be printed in French. Though the edition is included in Baudrier's Bibliographie lyonnaise, it has so far escaped the notice of specialists working on Gregory Nazianzen. What is important about the edition, however, is not that it is a bibhographical ‘first,’ but that it reveals some new dimensions of humanist interest in the early Fathers of the Church.

Of the three known copies of La cure et nourrissement des Pauvres, one is in the Bibliothèque publique et universitaire de Genève, where it is bound with another work printed by Gryphius in 1539, La Police de l’aulmosne de Lyon; a second belonged to Baudrier and was also bound with La Police de Vaulmosne; and the third is at the Archives de la Charité et de l'Hôtel-Dieu de Lyon.
Music Printing in Sixteenth-Century Strasbourg
Authors: Young William
Published: April 2006

One indication of the extent of musical activity in Strasbourg during the sixteenth century is the sizeable number and superior quality of collections of music and books about music printed there during the period. Scarcely fifty years after Gutenberg printed his first Bible at Mainz, a veritable flood of publications began to pour from the presses of Strasbourg. Although no Strasbourg printer devoted his talents exclusively to publishing music, several printers achieved a measure of prominence in the field. As a consequence of the printers’ diversity of material, the circle of individuals connected in some way with publishing included most of the leading writers, poets, clergymen, musicians, and artists of the day.

From the standpoint of sheer bulk alone hymnals or psalters merit first consideration. The advent of the Reformation in Strasbourg with services in the vernacular dating from 1524 accounts for the sudden interest in sacred music suitable for the congregation.
Some Renaissance Panegyrics of Aquinas
Authors: O'malley John W.
Published: April 2006

This year's commemoration of the seven-hundredth anniversary of the death of Aquinas in 1274 continues a tradition of veneration and panegyric which stretches far back into history and reaches considerably beyond the confines of the Dominican order to which the saint belonged. The most famous and provocative panegyric of St. Thomas is certainly that of Lorenzo Valla, delivered in the Dominican church of S. Maria sopra Minerva, Rome, on the saint's feast day, March 7, 1457. The fame, even notoriety, of this particular panegyric derives from the significant place in intellectual history which the panegyrist holds as well as from his curious treatment of his subject. As has frequently been observed, Valla's oration is almost an antipanegyric, an apologia for his own humanistic style of theology against the scholastic style of Thomas. It is a good illustration of the fundamental antagonisms between these two styles and an instance of the polemic which often marked their confrontation.
A Self Disciplining Pact Made by the Peruzzi Family of Florence (June 1433)
Authors: D. V.  , Kent F. W.
Published: April 2006

On a Thursday in June 1433 nine leaders of the Peruzzi family, one of Florence's biggest and most celebrated lineages, met in the house of Ridolfo di Bonifazio Peruzzi to discuss, as they had precisely four years earlier, how to prevent or if necessary how to deal with various offences—slanders, robberies, assaults or even murders—that might be committed by men of the Peruzzi against others. We know about these intriguing clan meetings, a response to the factional manoeuvring of the years 1426-34, from an unpublished document, formally recording the family's decision on 25 June 1433 to elect three of their number with “pieno e libero mandato da tutti gl'altri a potere procedere contro a qualunche persona facessi per l'innanzi alcuna villania, danno o dispiacere ad alcuna persona,” which survives in two seventeenth-century copies in the Archivio Peruzzi de' Medici, a private collection deposited in the Florentine State Archives in 1935.
Actin polymerization in neutrophils from donors of peripheral blood stem cells: Divergent effects of glycosylated and nonglycosylated recombinant human granulocyte colony‐stimulating factor
Authors: Carulli Giovanni , Mattii Letizia , Azzarà Antonio , Brizzi Stefania , Galimberti Sara , Zucca Alessandra , Benedetti Edoardo , Petrini Mario
Published: April 2006

Neutrophil functions can be modified by Recombinant human G‐CSF (rhG‐CSF) treatment, with divergent effects on phagocytosis, motility, bactericidal activity, and surface molecule expression. Neutrophil morphology is modified by treatment with filgrastim (the nonglycosylated form of rhG‐CSF), while it is not affected by lenograstim (the glycosylated type of rhG‐CSF). Little information is available about actin polymerization in neutrophils from subjects treated with the two types of rhG‐CSF. In the current paper we evaluated two groups of donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC; 15 blood donors were evaluated as a control group. Actin polymerization (both spontaneous and fMLP‐stimulated) was studied by a flow cytometric assay. A microscopic fluorescent assay was also carried out to evaluate F‐actin distribution in neutrophils. We found that filgrastim induced an increased F‐actin content in resting neutrophils, along with morphologic evidence for increased actin polymerization distributed principally at the cell membrane and frequently polarized in focal areas; in addition, fMLP was not able to induce further actin polymerization. On the contrary, treatment with lenograstim was associated with F‐actin content, distribution, and polymerization kinetics indistinguishable from those displayed by control neutrophils. Such experimental results show that filgrastim and lenograstim display divergent effects also on neutrophil actin polymerization and provide further explanation for previous experimental findings. Am. J. Hematol. 81:318–323, 2006. © 2006 Wiley‐Liss, Inc.
MATLAB as an introductory programming language
Authors: Wirth M. A. , Kovesi P.
Published: April 2006

This paper explores the use of MATLAB for teaching the fundamental constructs of programming languages to engineering and science students. It was found that the time taken for students to learn programming can be reduced by up to 50%, paving the way for using the language to solve problems. © 2006 Wiley Periodicals, Inc. Comput Appl Eng Educ 14: 20–30, 2006; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20064
Cover Picture: Design, Synthesis, and Characterization of Conifer‐Shaped Dendritic Architectures (Chem. Eur. J. 14/2006)
Authors: Newkome George R. , Kotta Kishore K. , Moorefield Charles N.
Published: April 2006

On the making of trees Joyce Kilmer wrote (1914) “I think that I shall never see a poem as lovely as a tree. …︁Poems are written by fools like me, But only God can make a tree.” However, to the synthetic organic chemist, Woody Allen is probably more appropriate: [Kilmer] “said that 'only God can make a tree,' probably because it's so hard to figure out how to get the bark on”. In their Full Paper on page 3726 ff., G. R. Newkome et al. describe the design, synthesis, and characterization of conifer‐shaped dendritic architectures.
Helium Atom Scattering from Oxide Surfaces
Authors: Traeger Franziska
Published: April 2006

Many experimental methods of surface science employ electrons or photons of considerable incident energy as probe particles. However, insulating surfaces or delicate physisorbed layers may be damaged by these particles and should, therefore, be analyzed with a gentler probe: He atom scattering allows to determine the symmetry of the unit cell and the detection of phase transitions from diffraction measurements as well as the determination of surface and adsorbate vibrations by time‐of‐flight resolved detection. Herein, the application of He atom scattering to oxide surfaces is demonstrated on the basis of the examples of MgO and ZnO. MgO(001) is a very inert and stable surface, whereas hydrogen atoms are chemisorbed on the mixed‐terminated ZnO(10$\bar 1$0) and on both polar faces: ZnO(000$\bar 1$) and ZnO(0001). He atom scattering is very sensitive to the presence of hydrogen on surfaces. In addition ZnO reacts with molecules such as water, CO and CO2. It is demonstrated that in combination with photoelectron spectroscopy and thermal desorption spectroscopy He atom scattering can also contribute to studies of surface chemistry.
Synthesis and Characterization of Two Silver Iodides with One‐ and Three‐Dimensional Hybrid Structures Constructed From Ag···Ag Interactions and Organic Templates
Authors: Li Hao‐Hong , Chen Zhi‐Rong , Li Jun‐Qian , Huang Chang‐Cang , Zhang Yong‐Fan , Jia Gui‐Xiao
Published: April 2006

Two new organically templated silver iodides, namely [(bmph)(Ag5I7)]n (1) and [(Hteda)4(Ag12I16)]n (2), have been synthesized with bmph2+ and teda [bmph2+ = 1,6‐bis(4‐methylpyridinio)hexane, Hteda = protonated triethylenediamine] as structure‐directing agents. Complex 1 consists of a one‐dimensional polymer that can be described as edge‐sharing AgI4 tetrahedra, whereas 2 is the first example of a three‐dimensional Ag/I framework based on Ag···Ag weak interactions and an organic template. Electrostatic interactions between the organic countercations and inorganic moieties are present and contribute to the crystal packing. Both compounds have been further characterized by IR spectroscopy, elemental analysis, TGA, and optical limiting measurements. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Human and nonhuman primate brains: Are they allometrically scaled versions of the same design?
Authors: Rilling James K.
Published: April 2006

Allometric analyses of brain structure sizes across the primate order demonstrate that human, ape, and other anthropoid brains are not simply allometrically scaled versions of the same generalized design. Both human and ape brains exhibit specializations with respect to other anthropoid brains. Ape specializations include elaboration of the cerebellum (all apes) and frontal lobes (great apes only), and probably connectivity between them. Human brain specializations include an overall larger proportion of neocortex, with disproportionate enlargement of prefrontal and temporal association cortices; an apparent increase in cerebellar connections with cerebral cortical association areas involved in cognition; and a probable augmentation of intracortical connectivity in prefrontal cortex.
Retrospective motion correction protocol for high‐resolution anatomical MRI
Authors: Kochunov Peter , Lancaster Jack L. , Glahn David C. , Purdy David , Laird Angela R. , Gao Feng , Fox Peter
Published: April 2006

Modern computational brain morphology methods require that anatomical images be acquired at high resolution and with a high signal‐to‐noise ratio. This often translates into long acquisition times (>20 minutes) and images susceptible to head motion. In this study we tested retrospective motion correction (RMC), common for functional MRI (fMRI) and PET image motion correction, as a means to improve the quality of high‐resolution 3‐D anatomical MR images. RMC methods are known to be effective for correcting interscan motion; therefore, a single high‐resolution 3‐D MRI brain study was divided into six shorter acquisition segments to help shift intrascan motion into interscan motion. To help reduce intrascan head motion, each segment image was reviewed for motion artifacts and repeated if necessary. Interscan motion correction was done by spatially registering images to the third image and forming a single average motion‐corrected image. RMC was tested on 35 subjects who were considered at high risk for head motion. Our results show that RMC provided better contrast‐to‐noise ratio and boundary detail when compared to nonmotion‐corrected averaged images. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Id1 is a critical mediator in TGF-β–induced transdifferentiation of rat hepatic stellate cells
Authors: Wiercinska Eliza , Wickert Lucia , Denecke Bernd , Said Harun M. , Hamzavi Jafar , Gressner A. M. , Thorikay Midori , ten Dijke Peter , Mertens Peter R. , Breitkopf Katja , Dooley Steven
Published: April 2006

Transforming growth factor (TGF)-β is critically involved in the activation of hepatic stellate cells (HSCs) that occurs during the process of liver damage, for example, by alcohol, hepatotoxic viruses, or aflatoxins. Overexpression of the TGF-β antagonist Smad7 inhibits transdifferentiation and arrests HSCs in a quiescent stage. Additionally, bile duct ligation (BDL)-induced fibrosis is ameliorated by introducing adenoviruses expressing Smad7 with down-regulated collagen and α-smooth muscle actin (α-SMA) expression. The aim of this study was to further characterize the molecular details of TGF-β pathways that control the transdifferentiation process. In an attempt to elucidate TGF-β target genes responsible for fibrogenesis, an analysis of Smad7-dependent mRNA expression profiles in HSCs was performed, resulting in the identification of the inhibitor of differentiation 1 (Id1) gene. Ectopic Smad7 expression in HSCs strongly reduced Id1 mRNA and protein expression. Conversely, Id1 overexpression in HSCs enhanced cell activation and circumvented Smad7-dependent inhibition of transdifferentiation. Moreover, knock-down of Id1 in HSCs interfered with α-SMA fiber formation, indicating a pivotal role of Id1 for fibrogenesis. Treatment of HSCs with TGF-β1 led to increased Id1 protein expression, which was not directly mediated by the ALK5/Smad2/3, but the ALK1/Smad1 pathway.

In vivo

, Id1 expression and Smad1 phosphorylation were co-induced during fibrogenesis.

In conclusion

, Id1 is identified as TGF-β/ALK1/Smad1 target gene in HSCs and represents a critical mediator of transdifferentiation that might be involved in hepatic fibrogenesis.

Supplementary material for this article can be found on the HEPATOLOGY website (

http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html

).

(Hepatology 2006;43:1032–1041.)
Adeno-associated virus-mediated expression of apolipoprotein (a) kringles suppresses hepatocellular carcinoma growth in mice
Authors: Lee Kyuhyun , Yun Sung-Tae , Kim Young-Gun , Yoon Yeup , Jo Eui-Cheol
Published: April 2006

Hepatocellular carcinoma (HCC) constitutes more than 90% of all primary liver cancers. HCC is a hypervascular tumor that develops from dedifferentiation of small avascular HCC and is therefore a good target for anti-angiogenic gene therapy. Recent studies have identified apolipoprotein(a) [apo(a)] kringles LK68 and LK8 (LKs) as having a potential anti-angiogenic and anti-tumor activity, and the current study evaluates the therapeutic potential of gene therapy with recombinant adeno-associated virus carrying genes encoding LKs (rAAV-LK) in the treatment of hypervascular HCC. We generated rAAV-LK to obtain persistent transgene expression

in vivo

, which is essential for anti-angiogenic therapy. The rAAV-produced LKs substantially inhibited proliferation and migration of human umbilical vein endothelial cells (HUVECs)

in vitro

, validating their anti-angiogenic potential. Intramuscular administration of rAAV-LK gave 60% to 84% suppression (

P

< .05) of tumor growth in mice bearing subcutaneously transplanted HCC derived from Huh-7 and Hep3B cells, respectively. Histological and immunohistochemical analyses of HCC tumor sections showed that a single administration of rAAV-LK gave rise to persistent expression of LKs that inhibited tumor angiogenesis and triggered tumor apoptosis, and, thus, significantly suppressed tumor growth. The administration of rAAV-LK provided a significant survival benefit (

P

< .05), and 3 of 10 rAAV-LK–treated mice were still alive without visible tumors and without clinical symptoms 188 days after treatment.

In conclusion,

rAAV-LK is a potential candidate for anti-angiogenic gene therapy in the treatment of HCC. (Hepatology 2006;43:1063–1073.)
Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon α-2a (40 kd)/ribavirin therapy
Authors: Jensen Donald M. , Morgan Timothy R. , Marcellin Patrick , Pockros Paul J. , Reddy Rajender K. , Hadziyannis Stephanos J. , Ferenci Peter , Ackrill Andrew M. , Willems Bernard
Published: April 2006

Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon α-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA <50 IU/mL) and a SVR (HCV RNA <50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients with than without a RVR (89% vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95% CI 4.2-22.5;

P

< .0001) or 200,000-600,000 IU/mL (OR 3.6, 95% CI 1.5-9.1;

P

= .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95% CI 0.9-3.7;

P

= .0954). RVR (OR 23.7 vs. no RVR, 95% CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. >600,000 IU/mL, 95% CI 1.1-6.3;

P

< .026) were significant and independent predictors of SVR in patients treated for 24 weeks.

In conclusion

, patients infected with HCV genotype 1 and treated with peginterferon α-2a/ribavirin sustained a RVR 24% of the time. This portends an 89% probability of a SVR after 24 weeks of treatment. (Hepatology 2006;43:954–960.)
Radiofrequency ablation for hepatocellular carcinoma in so-called high-risk locations
Authors: Teratani Takuma , Yoshida Haruhiko , Shiina Shuichiro , Obi Shuntaro , Sato Shinpei , Tateishi Ryosuke , Mine Norio , Kondo Yuji , Kawabe Takao , Omata Masao
Published: April 2006

We evaluated the efficacy and safety of radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in presumably high-risk locations. Between February 1999 and December 2001, we performed RF ablation on 1,419 nodules in 636 consecutive HCC patients, of which 231 nodules in 207 patients were in high-risk locations, defined as less than 5 mm from a large vessel or an extrahepatic organ. Eighty-one patients had a nodule adjacent to a large vessel, 145 patients had a nodule adjacent to an extrahepatic organ, of whom 19 also had one adjacent to a large vessel. Early complications and local tumor progression were analyzed with regard to the location of each nodule. The mean nodule diameter and average number per patient were 27 mm and 2.3, respectively. Early complications, within 30 days after ablation, occurred in 12 of 207 patients (5.8 %) with a nodule in a high-risk location and in 15 of 429 patients (3.5 %) without (

P

= .1776). There was no significant difference in local tumor progression rate between nodules in high-risk locations (1 year: 2.1%, 2 years: 3.1%, 3 years: 3.1%) and those elsewhere (1 year: 0.6%, 2 years: 1.7%, 3 years: 2.5%) (

P

= .2745).

In conclusion

, HCC nodules adjacent to a large vessel or extrahepatic organ were treated with RF ablation without compromising the efficacy of the procedure. However, even though without significant difference, some complications occurred at risky locations and need to be carefully considered. (Hepatology 2006;43:1101–1108.)
A novel multidrug-resistance protein 2 gene mutation identifies a subgroup of patients with primary biliary cirrhosis and pruritus
Authors: Floreani Annarosa , Carderi Isabella , Variola Angela , Rizzotto Erik Rosa , Nicol James , Bergasa Nora V.
Published: April 2006

A single nucleotide polymorphism characterized by the substitution of valine for glutamate (V1188E) in exon 25 of the multidrug resistance protein 2 gene was found in a group of patients with primary biliary cirrhosis. This heterozygous mutation was significantly associated with the presence of pruritus. (Hepatology 2006;43:1152–1154.)
A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B
Authors: Lee Hyo-Suk , Chung Young-Hwa , Lee KwanSik , Byun Kwan Soo , Paik Seung Woon , Han Joon-Yeol , Yoo Kwon , Yoo Hee-Won , Lee Jin Heon , Yoo Byung Chul
Published: April 2006

Clevudine is a nucleoside analog with an unnatural β-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n = 32), 30-mg clevudine (n = 32), and 50-mg clevudine (n = 34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (

P

< .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups.

In conclusion

, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels. (Hepatology 2006;43:982–988.)
Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver transplantation in Mdr2 +/− mice
Authors: Hoekstra Harm , Porte Robert J. , Tian Yinghua , Jochum Wolfram , Stieger Bruno , Moritz Wolfgang , Slooff Maarten J.H. , Graf Rolf , Clavien Pierre A.
Published: April 2006

Intrahepatic bile duct strictures are a serious complication after orthotopic liver transplantation (OLT). We examined the role of endogenous bile salt toxicity in the pathogenesis of bile duct injury after OLT. Livers from wild-type mice and mice heterozygous for disruption of the multidrug resistance 2 Mdr2 gene (Mdr2+/−) were transplanted into wild-type recipient mice. Mdr2+/− mice secrete only 50% of the normal amount of phospholipids into their bile, leading to an abnormally high bile salt/phospholipid ratio. In contrast to homozygous Mdr2−/− mice, the Mdr2+/− mice have normal liver histology and function under normal conditions. Two weeks after OLT, bile duct injury and cholestasis were assessed by light and electron microscopy, as well as through molecular and biochemical markers. There were no signs of bile duct injury or intrahepatic cholestasis in liver grafts from wild-type donors. Liver grafts from Mdr2+/− donors, however, had enlarged portal tracts with cellular damage, ductular proliferation, biliostasis, and a dense inflammatory infiltrate after OLT. Parallel to this observation, recipients of Mdr2+/− livers had significantly higher serum transaminases, alkaline phosphatase, total bilirubin, and bile salt levels, as compared with recipients of wild-type livers. In addition, hepatic bile transporter expression was compatible with the biochemical and histological cholestatic profile found in Mdr2+/− grafts after OLT.

In conclusion

, toxic bile composition, due to a high biliary bile salt/phospholipid ratio, acted synergistically with cold ischemia in the pathogenesis of bile duct injury after transplantation. (Hepatology 2006;43:1022–1031.)
Liver disease in Egypt: Hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors
Authors: Strickland Thomas G.
Published: April 2006

In Egypt, schistosomiasis was traditionally the most important public health problem and infection with

Schistosoma mansoni

the major cause of liver disease. From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook large control campaigns using intravenous tartar emetic, the standard treatment for schistosomiasis, as community-wide therapy. This commendable effort to control a major health problem unfortunately established a very large reservoir of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral drug, praziquantel, replaced tartar emetic as treatment for schistosomiasis in the entire country. This both reduced schistosomal transmission and disease and interrupted the “occult” HCV epidemic. It was evident when diagnostic serology became available in the 1990s that HCV had replaced schistosomiasis as the predominant cause of chronic liver disease. Epidemiological studies reported a high prevalence and incidence of HCV, particularly within families in rural areas endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co-infections with schistosomiasis caused more severe liver disease than infection with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV-specific T-cell responses leading to increased viral load, a higher probability of HCV chronicity, and more rapid progression of complications in co-infected persons. As complications of HCV usually occur after 20 years of infection, the peak impact of the Egyptian outbreak has not yet occurred. Efforts have been initiated by the Egyptian MOH to prevent new infections and complications of HCV in the estimated 6 million infected persons. (Hepatology 2006;43:915–922.)
A method for the effective formation of hepatocyte spheroids using a biodegradable polymer nanosphere
Authors: Gwak So‐Jung , Choi Dongho , Paik Seung Sam , Cho Seung‐Woo , Kim Sang‐Soo , Choi Cha Yong , Kim Byung‐Soo
Published: April 2006

Cultures of hepatocytes in spheroid form are known to maintain higher cell viability and exhibit better hepatocyte functions than those in monolayer cultures. In this study, a method for the formation of hepatocyte spheroids was developed using biodegradable polymer nanospheres. The addition of poly(lactic‐co‐glycolic acid) nanospheres to hepatocyte cultures in spinner flasks increased the efficiency of hepatocyte spheroid formation (the number of cells in spheroids divided by the total cell number) as compared with hepatocyte cultures without nanospheres (control). The viability and mitochondrial activity of the hepatocyte spheroids in the nanosphere‐added cultures were significantly higher than those in the control. In addition, the mRNA expression levels of albumin and phenylalanine hydroxylase, both of which are hepatocyte‐specific proteins, were significantly higher in the nanosphere‐added cultures than in the control. This new culture method improves upon the conventional method of forming hepatocyte spheroids in terms of spheroid formation efficiency, cell viability, and hepatocyte function. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum
Authors: Kumagai Takuji , Yoshikawa Tetsushi , Yoshida Mariko , Okui Toyo , Ihira Masaru , Nagata Nobuo , Yano Shoki , Shiraki Kimiyasu , Yamada Masao , Ichihara Kiyoshi , Asano Yoshizo
Published: April 2006

The time‐course of cell‐mediated immunity in exanthema subitum is not well documented. The lymphoproliferative response to purified human herpesvirus 6 (HHV‐6) antigen and to phytohemagglutinin was measured and natural killer (NK) cell activities determined in three consecutive specimens obtained biweekly from 18 young children and infants with exanthema subitum. Virus isolation and PCR detection of virus DNA and determination of neutralization antibody to HHV‐6 and ‐7 were also carried out. The magnitude of the HHV‐6 specific lymphoproliferative response varied; however, in most cases the time course kinetics revealed a low response in the acute phase with a subsequent gradual increase. In contrast, NK cell activities were high in the acute phase and declined gradually during convalescence. The lymphoproliferative response to phytohemagglutinin did not show a consistent trend in kinetics of time; however, dynamic changes in activity were observed in patients during the acute and convalescent periods. The results suggest that NK cells play a major role in resolving acute phase infection while specific lymphocyte activity develops later. The cause of the delayed development of HHV‐6 specific lymphoproliferative response is unknown. The lymphoproliferative response to phytohemagglutinin ratios implied that HHV‐6 infection has some impact on host T‐cell immunity during the course of exanthema subitum. J. Med. Virol. 78:792–799, 2006. © 2006 Wiley‐Liss, Inc.
HHV‐6 and HHV‐7 antigenemia related to CMV infection after liver transplantation
Authors: Härmä Maiju , Höckerstedt Krister , Lyytikäinen Outi , Lautenschlager Irmeli
Published: April 2006

Background

Betaherpesviruses human herpesvirus‐6 and ‐7 (HHV‐6, HHV‐7), which are closely related to cytomegalovirus (CMV), have been reported in transplant patients. In this retrospective study, we investigated the occurrence of HHV‐6 and HHV‐7 antigenemia in relation to symptomatic CMV infection after liver transplantation. Methods: Sample material from 64 adult liver transplant recipients was included in the study. The patients were monitored weekly for CMV, HHV‐6, and HHV‐7. CMV infections were diagnosed by pp65‐antigenemia and viral cultures. Concomitantly HHV‐6 and HHV‐7 antigens were demonstrated in peripheral blood mononuclear cells by monoclonal antibodies against both variants A and B and immunoperoxidase staining. Altogether 540 post‐transplant blood specimens were analyzed. Results: Nineteen patients (30%) developed symptomatic CMV pp65 antigenemia during the first 3 months (mean 33 days, range 5–62 days) post‐transplantation and were treated with intravenous ganciclovir. Concurrent HHV‐6 antigenemia was detected in 16/19 (median 9 days, range 6–24 days) and HHV‐7 antigenemia 15/19 patients (median 17 days, range 5–58 days) after transplantation. HHV‐6 appeared before CMV in most cases (12/16), HHV‐7 usually together with CMV. In those cases that HHV‐6 preceded CMV antigenemia, it also was a possible cause of graft dysfunction. HHV‐7 and CMV were so closely overlapping, that no symptoms could solely be linked with HHV‐7. Conclusion: HHV‐6 and HHV‐7 antigenemia usually occurred together with symptomatic CMV infection after liver transplantation. HHV‐6 preceded CMV, but HHV‐7 appeared together with CMV. Further investigation of the clinical significance of HHV‐6 and HHV‐7 antigenemia in organ transplant patients is necessary. J. Med. Virol. 78:800–805, 2006. © 2006 Wiley‐Liss, Inc.
Long‐term evaluation of rabbit peripheral nerve repair with end‐to‐side neurorrhaphy in rabbits
Authors: Zhang Zijie , Johnson Elizabeth O. , Vekris Marios D. , Zoubos Aristides B. , Bo Jinyan , Beris Alexandros E. , Soucacos Panayotis N.
Published: April 2006

This study was designed to quantitatively assess long‐term end‐to‐side neurorrhaphy in rabbits. The cut right ulnar nerve was repaired and sutured to the median nerve, in which a perineurial window was created in an end‐to‐side fashion 3 cm above the elbow joint. Both the extent of the reinnervation and the integrity of the intact donor nerve were evaluated in 36 rabbits randomly treated with fresh or delayed nerve repair. Evaluations included motor nerve conduction velocity (MNCV), dry muscle weight (DMW), and histological examinations at 9 and 12 months postoperatively. The recovery rates of MNCV were 90.1% and 92.8% for the ulnar nerve, and 95.7% and 96.8% for the median nerve, compared to intact contralateral nerves at 9 and 12 months, respectively. MNCV was not detectable for the ulnar nerve in control animals, while it was normal for the median nerve. Recoveries of flexor carpi ulnaris dry muscle weight of about 90.7% and 94.5% were observed at 9 and 12 months postoperatively, respectively. However, muscle mass measurements revealed a recovery of only 31.3% and 27% for control groups at 9 and 12 months postoperatively. The differences between experimental groups and control groups were statistically significant (P < 0.01). Neurofilament and silver stains showed numerous sprouting axons originating from the median nerve to the ulnar nerve. The results indicate that end‐to‐side neurorrhaphy could induce axonal sprouting from the main nerve trunk of upper limbs in rabbits, leading to useful functional recovery. © 2006 Wiley‐Liss, Inc. Microsurgery, 2006
Facial paralysis
Authors: Vlastou Catherine
Published: April 2006

Detailed knowledge of embryology, anatomy, and function of the facial nerve is essential in treating the devestating functional, aesthetic, and psychological sequelae of facial paralysis. Two basic factors influence the method of repair and the subsequent outcome of the effort to combat facial paralysis. First is the availability of a viable proximal nerve stump which can be used as the source for motor axons, and which is related to the level of the injury. Second is the duration of the paralysis, which will dictate the possibility of reinnervating the facial muscles. Early restoration of nerve continuity, and therefore reestablishment of the neuromuscular junction and preservation of the function of the facial muscles, lead to superior functional and aesthetic rehabilitation. Secondary reconstruction, after the establishment of atrophy of the motor endplates of the facial muscles, is possible with nerve grafts and microsurgical free functional muscle transfer. These techniques, although not perfect, greatly improve aesthetic balance and alleviate the functional and psychological implications of the paralysis.© 2006 Wiley‐Liss, Inc. Microsurgery, 2006
Musculocutaneous neurotization to restore elbow flexion in brachial plexus paralysis
Authors: Vekris Marios D. , Beris Alexandros E. , Johnson Elizabeth O. , Korobilias Anastasios V. , Pafilas Dimitrios , Vekris Anastasios D. , Soucacos Panayotis N.
Published: April 2006

Brachial plexus injuries may result in devastating paralysis, especially if they involve all the roots. The upper roots are often traumatized, and therefore elbow flexion is usually lost. The prognosis of these injuries is grave if root avulsions are present and the paralysis includes the hand as well. The current management of brachial plexus injuries should be early, aggressive microsurgical reconstruction of the plexus, combining various neurotizations with intraplexus and extraplexus nerve donors. Following this principle, we present the results of musculocutaneous neurotization in our unit, as well as a review of the literature on this subject. Our results are comparable to those reported in the literature, and indicate that the strongest function is achieved after neurotization via intraplexus donors, while some extraplexus donors (i.e., phrenic and accessory nerve) can offer equally strong elbow flexion, especially if they are used in combination. Neurotization of the musculocutaneous nerve should be one of the primary goals in the reconstruction of the injured plexus, since the return of elbow flexion is of paramount importance in daily activity. The restoration of function is ensured if the stronger and healthier motor donors are dedicated to the neurotization of the musculocutaneous nerve. Sometimes in order to match the axonal number of the target to the lower number of axons offered by the donors, two or more donor nerves may be driven to the same target, such as the musculocutaneous nerve. © 2006 Wiley‐Liss, Inc. Microsurgery, 2006
Ifosfamide‐induced nephrotoxicity in 593 sarcoma patients: A report from the Late Effects Surveillance System
Authors: Stöhr W. , Paulides M. , Bielack S. , Jürgens H. , Treuner J. , Rossi R. , Langer T. , Beck J.D.
Published: April 2006

Background

Ifosfamide is widely used in paediatric oncology, but its use is limited by nephrotoxic side effects. The aim of this study was to evaluate the incidence and risk factors of tubulopathy, with special emphasis on the influence of age, where different findings have been published so far.

Procedure

Five hundred ninety three children and adolescents treated for Ewing, osteo‐ or soft‐tissue sarcoma (median age at diagnosis: 11.7 years) were prospectively investigated for nephrotoxicity in the Late Effects Surveillance System (LESS) study. Tubulopathy was diagnosed in case of continuing hypophosphatemia and proteinuria.

Results

After a median follow up of 19 months, 27 patients (4.6%; 95% CI: 3.0–6.6%) had newly developed tubulopathy. This incidence was 0.4% (95% CI: 0–2.4%) in patients treated with a cumulative ifosfamide dose of ≤24 g/m2, 6.5% (95% CI: 3.6–10.7%) after 24–60 g/m2, and 8.0% (95% CI: 4.2–13.6%) after ≥60 g/m2. In multivariate analysis, children younger than 4 years at time of diagnosis had an 8.7‐fold (95% CI: 3.5–21.8) higher risk for tubulopathy than older patients. Neither carboplatin treatment nor abdominal irradiation showed any significant influence.

Conclusion

Ifosfamide‐induced nephrotoxicity was found in 4.6% of patients. Risk factors were the cumulative ifosfamide dose and young age at treatment. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
Ion sampling effects under conditions of total solvent consumption
Authors: Schneider Bradley B. , Javaheri Hassan , Covey Thomas R.
Published: April 2006

The motivation of this work was to study some of the properties of nanoelectrospray operation under conditions where the entire sprayed liquid is vaporized and inhaled into the vacuum system. Under these conditions the desolvation requirements, sampling efficiency, concentration versus mass sensitivity, and molar response characteristics of various compounds were studied. The combined efficiency of ion production from solution and transfer into the vacuum system, referred to as sampling efficiency, is presented under various inlet conditions including different flow rates, solution compositions, and compound types. Under ideal solvent conditions the results for favorable compounds show sampling efficiencies of 70–85% at flows in the range of 50–500 nL/min. Efficiencies were lower for aqueous samples and compounds of different structures gave different molar response factors under these high sampling efficiency conditions. The relative molar response factors are presented in terms of those observed with higher flow rate sources which operate at significantly lower sampling efficiencies. In all cases, operating in this flow regime, the ion count rate was directly proportional to the absolute mass of analyte molecules entering the source. The experimental source used to carry out these studies included gas nebulization to stabilize the electrospray process, a heated laminar flow chamber to enhance desolvation and ion production, and various atmosphere‐to‐vacuum aperture diameters to maximize ion transfer. Copyright © 2006 John Wiley & Sons, Ltd.
A state space embedding approach to approximate feedback linearization of single input nonlinear control systems
Authors: Deutscher Joachim , Schmid Christian
Published: April 2006

This contribution presents a numerical approach to approximate feedback linearization which transforms the Taylor expansion of a single input nonlinear system into an approximately linear system by considering the terms of the Taylor expansion step by step. In the linearization procedure, higher degree terms are taken into account by using a state space embedding such that the corresponding system representation has not to be computed in every linearization step. Linear matrix equations are explicitly derived for determining the nonlinear change of coordinates and the nonlinear feedback that approximately linearize the nonlinear system. If these linear matrix equations are not solvable, a least square solution by applying the Moore–Penrose inverse is proposed. The results of the paper are illustrated by the approximate feedback linearization of an inverted pendulum on a cart. Copyright © 2006 John Wiley & Sons, Ltd.
Threshold setting and the cycling of a decision threshold
Authors: Weaver Elise A. , Richardson George
Published: April 2006

When policy‐makers use a test result with a cut‐off score in a decision, the cut‐off threshold may change over time. An example is the threshold of “reasonable suspicion” used to justify a police search. Hammond (1996) postulated that a decision threshold will oscillate over time in response to competing pressures from affected constituencies, as unavoidable cases of false positives (e.g., innocent people searched) and false negatives (e.g., guilty people overlooked) emerge from the uncertainty of using an imperfect test (e.g., level of evidence) to predict the actual measure of interest (e.g., guilt). The structural underpinnings of a cycling threshold are analyzed in this theory‐building article. First, we present a simplified converging model of Hammond's initial insight. Then, we present three alternative models: a model with delays in policy‐maker responsiveness; one with stakeholders' shifting constituencies in response to recent errors; and one with integral control representing the historical dissatisfaction of competing constituencies. The “history” model meets the theoretical requirements set out by Hammond and fits historical data regarding FBI denials of access to information regarding a third party due to privacy concerns. Copyright © 2006 John Wiley & Sons, Ltd.
Involvement of Na+/H+ exchanger in the calcium signaling in epimastigotes of Trypanosoma cruzi
Authors: Bollo Mariana , Bonansea Sergio , Machado Estela E.
Published: April 2006

We studied the effect of Na+ extracellular on Ca2+ mobilization from intracellular store evoked by carbachol in Trypanosoma cruzi. We report that slow component of Ca2+ signaling evoked by agonist is dependent on extracellular Na+ but not on InsP
3 increase. Moreover, this Ca2+ signaling progressively increased when pH of the medium changed from 7.0 to 7.8. In addition, we found that it was regulated by PKC. The agonist was also able to induce the alkalinization of the acidic compartment, and both Ca2+ signaling and alkalinization were inhibited by the EIPA‐inhibitor of the Na+/H+ exchanger. These results demonstrated the alkalinization of acidic vacuoles and PKC are involved in the triggering of the epimastigote Ca2+ signaling.
Crystal structure of AmyA lacks acidic surface and provide insights into protein stability at poly‐extreme condition
Authors: Sivakumar Neelamegam , Li Nan , Tang Julian W. , Patel Bharat K.C. , Swaminathan Kunchithapadam
Published: April 2006

Here we report the first crystal structure of a protein, AmyA, a secretory α‐amylase isolated from Halothermothrix orenii, which is both halophilic and thermophilic. The crystal structure was determined at 1.6 Å resolution. AmyA lacks the conserved acidic surface, which is considered essential for protein stability at high salinity. Sedimentation velocity and CD experiments on AmyA reveal the formation of unique reversible poly‐dispersed oligomers that show unusually high thermal stability. These studies provide valuable insight into the structural elements that contribute to the stability of AmyA at both physical and chemical extremes and their functional implications.