bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre‐ and post‐dialysis quantitative dosage of thymidine in urine and plasma of a MNGIE patient by using HPLC‐ESI‐MS/MS
Authors: la Marca G. , Malvagia S. , Casetta B. , Pasquini E. , Pela I. , Hirano M. , Donati M. A. , Zammarchi E.
Published: February 2006

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by severe gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. The disease is due to a thymidine phosphorylase defect. This enzyme catalyses the phosphorolysis of thymidine to thymine and deoxyribose 1‐phosphate. For this reason, increased levels of thymidine in plasma and urine are found in MNGIE patients. Haemodialysis can reduce circulating plasma thymidine levels and can be beneficial in some MNGIE patients. We developed a fast analytical method based on HPLC‐ESI‐MS/MS capable of identifying pyrimidine nucleotides (thymine, cytosine, uracil) and nucleosides (thymidine, citidine, uridine) in plasma and urine after direct dilution of the samples without pre‐treatment.

In the patient studied, we observed a significant reduction of plasmatic and urinary thymidine levels during and after dialysis. However, we noted a progressive reduction of the initial thymidine level after some dialytic trials. This method will be useful not only for thymidine level follow‐up during dialysis in MNGIE patients but also for the improvement of the diagnosis or diagnostic suspect in other pyrimidine defects such as dihydropyrimidine dehydrogenase deficiency, dihydropyrimidinase deficiency and ureidopropionase deficiency. Copyright © 2006 John Wiley & Sons, Ltd.
Collision‐induced dissociation pathways of yeast sphingolipids and their molecular profiling in total lipid extracts: a study by quadrupole TOF and linear ion trap–orbitrap mass spectrometry
Authors: Ejsing Christer S. , Moehring Thomas , Bahr Ute , Duchoslav Eva , Karas Michael , Simons Kai , Shevchenko Andrej
Published: February 2006

The yeast Saccharomyces cerevisiae synthesizes three classes of sphingolipids: inositolphosphoceramides (IPCs), mannosyl‐inositolphosphoceramides (MIPCs), and mannosyl‐diinositolphosphoceramides (M(IP)2C). Tandem mass spectrometry of their molecular anions on a hybrid quadrupole time‐of‐flight (QqTOF) instrument produced fragments of inositol‐containing head groups, which were specific for each lipid class. MSn analysis performed on a hybrid linear ion trap–orbitrap (LTQ Orbitrap) mass spectrometer with better than 3 ppm mass accuracy identified fragment ions specific for the amide‐linked fatty acid and the long chain base moieties in individual molecular species. By selecting m/z of class‐specific fragment ions for multiple precursor ion scanning, we profiled yeast sphingolipids in total lipid extracts on a QqTOF mass spectrometer. Thus, a combination of QqTOF and LTQ Orbitrap mass spectrometry lends itself to rapid, comprehensive and structure‐specific profiling of the molecular composition of sphingolipids and glycerophospholipids in important model organisms, such as fungi and plants. Copyright © 2006 John Wiley & Sons, Ltd.
Gender differences in response of hippocampus to chronic glucocorticoid stress: Role of glutamate receptors
Authors: Liu Howard H. , Payne H. Ross , Wang Bin , Brady Scott T.
Published: February 2006

Glucocorticoids (GC) play critical roles in the pathophysiological reactions to environmental stress. In brain, morphological changes were examined in hippocampal CA3 neurons with 2 weeks of chronic elevation of GC in male and female mice. Molecular correlates and underlying mechanisms paralleling these morphologic changes in hippocampus were investigated. Although the hippocampal neurons in the CA3 area in male mice atrophy with chronically elevated GC, female mice show minimal morphological changes with comparable GC regimens. These sexual morphological differences correlate with differences in the postsynaptic dense protein (PSD95) as well as the spectrum of glutamate receptors induced by GC treatment in male and female mice, including NMDA, AMPA, and KA receptors. These findings suggest that synaptic receptor composition is adapted to the unique physiological requirements of males and females and illuminate underlying mechanisms of GC/stress responses in the brain. © 2006 Wiley‐Liss, Inc.
Effects of Lamotrigine on field potentials, propagation, and long‐term potentiation in rat prefrontal cortex in multi‐electrode recording
Authors: Huang Chin‐Wei , Hsieh Yi‐Jung , Tsai Jing‐Jane , Huang Chao‐Ching
Published: February 2006

Lamotrigine (LTG) is an anti‐epileptic drug that is widely used clinically in various neuropsychiatric disorders. Although consensus is found on the general mode of action by LTG on voltage‐gated sodium current, its effect on field potential, neuropropagation, and long‐term potentiation, especially in prefrontal cortex (PFC), is still not understood completely. We investigated LTG effects on synaptic response in rat prefrontal cortical slice with the aid of a novel multi‐electrode dish (MED64) system. The amplitude and propagation of field excitatory postsynaptic potentials (fEPSP), presynaptic fiber volleys (PrV) were expressed dimensionally in the MED64 system. Lamotrigine (3–100 μM) inhibited the amplitude and propagation of fEPSP and PrV in a concentration dependent manner. It exerted a predominant presynaptic action, as indicated by the increment in paired‐pulse facilitation. Stimulating dependency with reduction fEPSP was seen in the presence of LTG at clinically relevant concentrations as well as with PrV, both in amplitude and propagation. In addition, the depression of PrV amplitudes in the presence of LTG showed a use‐dependent fashion. As to LTP in PFC, it was not fEPSP amplitude but propagation reduced by LTG. In PFC, LTG exerts its use‐ and concentration‐dependent inhibitory effect on presynaptic action and depresses fEPSP amplitude and propagation in a clinically relevant concentration. LTP was preserved in its fEPSP amplitude but not propagation in PFC in the presence of LTG. © 2006 Wiley‐Liss, Inc.
Glutamate receptor agonist kainate enhances primary dendrite number and length from immature mouse cortical neurons in vitro
Authors: Monnerie Hubert , Le Roux Peter D.
Published: February 2006

Glutamate is an important regulator of dendrite development that may inhibit, (during ischemic injury), or facilitate (during early development) dendrite growth. Previous studies have reported mainly on the N‐methyl‐D‐aspartate (NMDA) receptor‐mediated dendrite growth‐promoting effect of glutamate. In this study, we examined how the non‐NMDA receptor agonist kainate influenced dendrite growth. E18 mouse cortical neurons were grown for 3 days in vitro and immunolabeled with anti‐microtubule‐associated protein 2 (MAP2) and anti‐neurofilament (NF‐H), to identify dendrites and axons, respectively. Exposure of cortical neurons to kainate increased dendrite growth without affecting neuron survival. This effect was dose‐dependent, reversible and blocked by the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionate (AMPA)/kainate receptor antagonist NBQX and the low‐affinity kainate receptor antagonist NS‐102, but not by the AMPA receptor antagonist CFM‐2. In addition, the NMDA receptor antagonist MK‐801 had no effect on kainate‐induced dendrite growth. Immunolabeling and Western blot analysis of kainate receptors using antibodies against the GluR6 and KA2 subunits, demonstrated that the immature cortical neurons used in this study express kainate receptor proteins. These results suggest that kainate‐induced non‐NMDA receptor activation promotes dendrite growth, and in particular primary dendrite number and length, from immature cortical neurons in vitro, and that kainate receptors may be directly involved in this process. Furthermore, these data support the possibility that like NMDA receptors, kainate receptor activation may also contribute to early neurite growth from cortical neurons in vitro. © 2006 Wiley‐Liss, Inc.
Ataxin 10 induces neuritogenesis via interaction with G‐protein β2 subunit
Authors: Waragai Masaaki , Nagamitsu Shinichiro , Xu Weidong , Li Yu Jiang , Lin Xi , Ashizawa Tetsuo
Published: February 2006

Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited disorder caused by an intronic ATTCT pentanucleotide repeat expansion. The ATXN10 gene encodes a novel protein, ataxin 10, known previously as E46L, which is widely expressed in the brain. Ataxin 10 deficiency has been shown recently to cause increased apoptosis in primary cerebellar cultures, thus implicated in SCA10 pathogenesis. The biologic functions of ataxin 10 remain largely unknown. By using yeast‐two‐hybrid screening of a human brain cDNA library, we identified the G‐protein β2 subunit (Gβ2) as an ataxin 10 binding partner, and the interaction was confirmed by coimmunoprecipitation and colocalization in mammalian cells in culture. Overexpression of ataxin 10 in PC12 cells induced neurite extension and enhanced neuronal differentiation induced by nerve growth factor (NGF). Moreover, coexpression of ataxin 10 and Gβ2 potently activated the Ras‐MAP kinase‐Elk‐1 cascade. Dominant negative Ras or inhibitor of MEK‐1/2 (U0126) aborted this activation, and blocked morphologic changes, whereas inhibition of TrkA receptor by K252a had no effects. Our data suggest that the ataxin 10‐Gβ2 interaction represents a novel mechanism for inducing neuritogenesis in PC12 cells by activating the Ras‐MAP kinase‐Elk‐1 cascade. © 2006 Wiley‐Liss, Inc.
Kinetics of the uptake of SO2 on mineral oxides: Improved initial uptake coefficients at 298 K from pulsed Knudsen cell experiments
Authors: Seisel Sabine , Keil Thorsten , Lian Yu , Zellner Reinhard
Published: February 2006

The uptake of SO2 on γ‐Fe2O3, γ‐Al2O3, and Saharan dust has been studied at T = 298 K using a Knudsen cell reactor operated in a steady‐state as well as in a pulsed mode. The initial uptake coefficients determined in the steady‐state mode have been found to be affected by surface saturation as well as bulk diffusion of SO2 resulting in an apparent dependence of the initial uptake coefficients on the sample mass of the mineral oxides. However, by operating the Knudsen cell in the pulsed mode with shorter response time, these effects could be suppressed. Initial uptake coefficients of γini (Fe2O3) = (8.8 ± 0.4) × 10−2, γini (Al2O3) = (7.4 ± 0.9) × 10−3, and γini (Saharan dust) = (7.6 ± 0.5) × 10−2 were derived. This suggests that Fe2O3 is an important component in determining the reactivity of mineral dusts. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 242–249, 2006
Rate constant estimation for C1 to C4 alkyl and alkoxyl radical decomposition
Authors: Curran H. J.
Published: February 2006

Rate coefficients for alkyl and alkoxy radical decomposition are important in combustion, biological, and atmospheric processes. In this paper, rate constant expressions for C1C4 alkyl and alkoxy radicals decomposition via β‐scission are recommended based on the reverse, exothermic reaction, the addition of a hydrogen atom or an alkyl radical to an olefin or carbonyl species with the decomposition reaction calculated using microscopic reversibility. The rate expressions have been estimated based on a wide‐range study of available experimental data. Rate coefficients for hydrogen atom and alkyl radical addition to an olefin show a strong temperature curvature. In addition, it is found that there is a correlation between the activation energy for addition and (i) the type of atom undergoing addition and (ii) whether this radical adds to the internal or terminal carbon atom of the olefin. Rate coefficients for alkoxy radical decomposition show a strong correlation to the ionization potential of the alkyl radical leaving group and on the enthalpy of reaction. It is shown that the activation energy for alkyl radical addition to a carbonyl species can be estimated as a function of the alkyl radical ionization potential and enthalpy of reaction. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 250–275, 2006
Rate coefficients for the reaction of OH with OClO between 242 and 392 K
Authors: Gierczak Tomasz , Burkholder James B. , Ravishankara A. R.
Published: February 2006

Rate coefficients are reported for the gas phase reaction of OH with OClO over the temperature range 242–392 K at 25, 50, and 100 Torr (He). Kinetic measurements were made using pulsed laser photolysis with laser induced fluorescence detection of the OH radical. The measured rate coefficients were independent of pressure and are well represented by k1(T) = (1.43 ± 0.3) × 10−12 exp(597 ± 36/T) cm3 molecule−1 s−1 (k1(298 K) = 1.06 × 10−11 cm3 molecule−1 s−1). The quoted uncertainties are 2σ (95% confidence level) and include estimated systematic errors. Discrepancies with the previous OH + OClO rate coefficient measurement by Poulet et al. (Int J Chem Kinet 1986, 18, 847–859) are discussed. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 234–241, 2006
Experimental and modeling study of the oxidation of xylenes
Authors: Battin‐Leclerc F. , Bounaceur R. , Belmekki N. , Glaude P. A.
Published: February 2006

This paper describes an experimental and modeling study of the oxidation of the three isomers of xylene (ortho‐, meta‐, and para‐xylenes). For each compound, ignition delay times of hydrocarbon–oxygen–argon mixtures with fuel equivalence ratios from 0.5 to 2 were measured behind reflected shock waves for temperatures from 1330 to 1800 K and pressures from 6.7 to 9 bar. The results show a similar reactivity for the three isomers. A detailed kinetic mechanism has been proposed, which reproduces our experimental results, as well as some literature data obtained in a plug flow reactor at 1155 K showing a clear difference of reactivity between the three isomers of xylene. The main reaction paths have been determined by sensitivity and flux analyses and have allowed the differences of reactivity to be explained. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 284–302, 2006
UV absorption spectra and self‐reaction rate constants for primary peroxy radicals arising from the chlorine‐initiated oxidation of carbonyl compounds
Authors: Crane J. P. Le , Villenave E.
Published: February 2006

A flash photolysis setup coupled to UV absorption spectrometry detection was used to measure the UV absorption spectra of the (CH3)2(CH2O2.)CC(O)C(CH3)3 and (CH3)2(CH2O2.)CC(O)CH3 radicals between 207 and 290 nm. The self‐reaction rate constants of these radicals were measured at 298 K: k((CH3)2(CH2O2.)CC(O)C(CH3)3 + (CH3)2(CH2O2.)CC(O)C(CH3)3) = (4.57 ± 0.38) × 10−12 cm3 molecule−1 s−1; k((CH3)2(CH2O2.) CC(O)CH3 + (CH3)2(CH2O2.)CC(O)CH3) = (4.77 ± 0.35) × 10−12 cm3 molecule−1 s−1, where quoted uncertainties only represent 2σ errors. Because of the similarities in both UV spectra and self‐reaction kinetics between (CH3)2(CH2O2.)CC(O)C(CH3)3 and (CH3)2(CH2O2.)CC(O)CH3 radicals, it was suggested to extend this results to all (CH3)2(CH2O2.)CC(O)R peroxy radicals (with R = H, alkyl), arising from the chlorine‐initiated oxidation of carbonyl compounds. This trend has been tested successfully in the case of the Cl‐initiated oxidation of pivalaldehyde (Le Crâne et al., J Phys Chem A 2004, 108, 795). © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 276–283, 2006
The nature and extent of landscape change under land resettlement programmes in Zimbabwe
Authors: Elliott J. A. , Burnside N. G. , Broomhead T. , Kinsey B. H. , Kwesha D.
Published: February 2006

Issues of land and further resettlement are central within the inter related crises that Zimbabwe is currently understood to be experiencing. This paper presents objective data that has not been available to date, concerning the landscape outcomes of the resettlement programme in Zimbabwe as it was implemented in the first two decades after independence. Sequential aerial photograph interpretation and GIS techniques are used to document and explore spatial patterns of resource use, landscape structure and change. Based on 21 resettlement villages across three scheme areas, the analysis explicitly considers the role of national drivers (of the relatively consistent policy and procedures during that time), of agro‐ecology and of multidirectional transformations at the village level to raise understanding of these outcomes. The implications of these findings and the value of the methodological techniques for the design and monitoring of further resettlement in the country and the wider region are suggested. Copyright © 2006 John Wiley & Sons, Ltd.
Land use and soil erosion in the upper reaches of the Yangtze River: some socio‐economic considerations on China's Grain‐for‐Green Programme
Authors: Long H. L. , Heilig G. K. , Wang J. , Li X. B. , Luo M. , Wu X. Q. , Zhang M.
Published: February 2006

Soil erosion in the upper reaches of the Yangtze River in China is a major concern and the Central Government has initiated the Grain‐for‐Green Programme to convert farmland to forests and grassland to improve the environment. This paper analyses the relationship between land use and soil erosion in Zhongjiang, a typical agricultural county of Sichuan Province located in areas with severe soil erosion in the upper reaches of the Yangtze River. In our analysis, we use the ArcGIS spatial analysis module with detailed land‐use data as well as data on slope conditions and soil erosion. Our research shows that the most serious soil erosion is occurring on agricultural land with a slope of 10∼25 degrees. Both farmland and permanent crops are affected by soil erosion, with almost the same percentage of soil erosion for corresponding slope conditions. Farmland with soil erosion accounts for 86·2 per cent of the total eroded agricultural land. In the farmland with soil erosion, 22·5 per cent have a slope of < 5 degrees, 20·3 per cent have a slope of 5∼10 degrees, and 57·1 per cent have a slope of > 10 degrees. On gentle slopes with less than 5 degrees inclination, some 6 per cent of the farmland had strong (5000∼8000 t km−2 y−1) or very strong (8000∼15000 t km−2 y−1) erosion. However, on steep slopes of more than 25 degrees, strong or very strong erosion was reported for more than 42 per cent of the farmland. These numbers explain why the task of soil and water conservation should be focused on the prevention of soil erosion on farmland with steep or very steep slopes. A Feasibility Index is developed and integrated socio‐economic assessment on the feasibility of improving sloping farmland in 56 townships and towns is carried out. Finally, to ensure the success of the Grain‐for‐Green Programme, countermeasures to improve sloping farmland and control soil erosion are proposed according to the values of the Feasibility Index in the townships and towns. These include: (1) to terrace sloping farmland on a large scale and to convert farmland with a slope of over 25 degrees to forests or grassland; (2) to develop ecological agriculture combined with improving the sloping farmland and constructing prime farmland and to pay more attention to improving the technology for irrigation and cultivation techniques; and (3) to carry out soil conservation on steep‐sloping farmland using suggested techniques. In addition, improving ecosystems and the inhabited environment through yard and garden construction for households is also an effective way to prevent soil erosion. Copyright © 2006 John Wiley & Sons, Ltd.
A laboratory study on the relative stability of the check‐dam system in the Loess Plateau, China
Authors: Xu X. Z. , Zhang H.‐W. , Wang G.‐Q. , Peng Y. , Zhang O. Y.
Published: February 2006

The building of check‐dams is one of the most effective measures for the conservation of soil and water in the Loess Plateau of China, and the hydro‐sedimentologic balance is the most important factor influencing the relative stability of the check‐dam systems. This means that the soil and water in small watersheds controlled by the check‐dams will be absorbed internally, without the need for raising the height of the dams, if some given parameters have reached certain values. A runoff simulation experiment for a single check‐dam and a rainfall simulation experiment for the whole check‐dam system has been conducted, and the runoff/rainfall intensity and the parameter RV were determined through the annual erosion rate of the prototype watershed. The results indicated that the raising of the dam‐land altitude became slower, and the mean gradient of the gully was kept at a constant. The main reasons causing the check‐dam to show a good relative stability are the enlarging of the dam‐land area, the alleviating of erosion by the check‐dam, and the auto‐stabilizing mechanism of the gullies.

This study presents a kind of scale‐down model experiment in which the ratio of the model geomorphological variable to the corresponding prototype variable keeps constant after the determinate runs of rainfalls, so that the soil and water erosion processes of the prototype could be monitored from the results of the model experiment. Four measures have been suggested for ensuring this ratio is a constant: (1) A bare‐land model with an appropriate erosion rate should be used in the experiment. (2) Dimensions of the landform, including the check‐dam, should normally be scaled down according to the prototype watershed. (3) Soil similar to those of the prototype should be used. (4) The antecedent water content before each rainfall simulation should be kept constant. Copyright © 2006 John Wiley & Sons, Ltd.
Thrombopoietin in postoperative thrombocytopenia following living donor hepatectomy
Authors: Nagasako Yoshihide , Jin Meang Bong , Miyazaki Hiroshi , Nakayama Masato , Shimamura Tsuyoshi , Furukawa Hiroyuki , Matushita Michiaki , Todo Satoru
Published: February 2006

Thrombocytopenia is a frequent finding following living donor hepatectomy. It appears more pronounced in right graft donors than in left graft donors. This study analyzed postoperative thrombocytopenia in 20 living liver donors and examined the change of endogenous thrombopoietin (TPO) in its recovery. Platelet count, TPO level, fibrinogen degradation product (FDP), and D-Dimer were measured before surgery and on postoperative days (PODs) 1, 2, 3, 5, 7, and 14. Concurrently, liver and spleen volumes were calculated by computed tomography. Platelet count on POD 3 was significantly lower in right graft donors than in left graft donors (13.0 ± 3.7 × 104/μL vs. 16.8 ± 4.0 × 104/μL, P = 0.039) but recovered by POD 7 in all donors. Postoperative elevations of FDP and D-Dimer were significantly higher in right graft donors than in left graft donors. TPO level rose immediately after surgery, peaked on POD 5 in left graft donors and on POD 7 in right graft donors, and fell nearly to preoperative levels by POD 14. Postoperative TPO level per liver volume was significantly higher in right graft donors than in left graft donors. In conclusion, thrombocytopenia following living donor hepatectomy resolved within the first week regardless of graft type and was mainly associated with increasing consumption of circulating platelets, possibly due to intrahepatic and splenic congestion. With a reduced number of circulating platelets, TPO level rapidly increases. Also, with reduced consumption of platelets related to recovery from surgery, thrombocytopenia should resolve. As a consequence, TPO level would be expected to fall.
Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation
Authors: Haga Hironori , Egawa Hiroto , Fujimoto Yasuhiro , Ueda Mikiko , Miyagawa-Hayashino Aya , Sakurai Takaki , Okuno Tomoko , Koyanagi Itsuko , Takada Yasutsugu , Manabe Toshiaki
Published: February 2006

Complement C4d deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in kidney and other solid organ transplantation. The correlation of C4d deposits and humoral rejection in liver transplants, however, is not well understood. We investigated the C4d immunostaining pattern in 34 patients whose liver biopsy was taken within the first 3 postoperative weeks for suspected acute rejection after ABO blood type-incompatible liver transplantation. The staining pattern was classified as positive (portal stromal staining), indeterminate (endothelial staining only), and negative (no staining). Positive C4d immunostaining was seen in 17 (50%) patients and was significantly associated with high (×64 or more) postoperative antidonor A/B antibody (immunoglobulin M (IgM)) titers (88 vs. 35%, P = 0.002) and poorer overall survival rate (41 vs. 88%, P = 0.007). Ten of 11 (91%) cases with histological acute humoral rejection (periportal edema and necrosis (PEN) or portal hemorrhagic edema) were positive for C4d, all of which showed high postoperative antibody titers. The other histologies associated with C4d positivity was purulent cholangitis (n = 4), coagulative hepatocyte necrosis (n = 1), acute cellular rejection (n = 1), and hepatocanalicular cholestasis (n = 1). Full clinical recovery was observed in only 6 of 17 (35%) C4d-positive patients, and tended to be associated with a lower rejection activity index (RAI). In conclusion, our study indicates that C4d deposits in the portal stroma can be a hallmark of acute humoral rejection in ABO-incompatible liver transplantation, and allograft damage can be reversible in a minority of cases.
Natural killer cells: Primary target for hepatitis C virus immune evasion strategies?
Authors: Golden-Mason Lucy , Rosen Hugo R.
Published: February 2006

Liver cirrhosis and hepatocellular carcinoma secondary to chronic hepatitis C virus (HCV) infection requiring transplantation represents a significant public health problem. The most remarkable feature of hepatitis C virus is the ability to establish chronic infection in the vast majority of cases. Efforts to define clinical correlates of HCV persistence have focused primarily on CD4 and CD8 T cell responses. Until recently, the role of innate immunity in determining the outcome of HCV infection had received relatively little attention. Natural killer (NK) cells are an important antiviral effector population eliminating virus through direct killing and cytokine production. Recent studies highlighting the cross-talk between NK cells, dendritic cells (DCs) and T cells have prompted reevaluation of the important role NK cells play in regulating and maintaining specific immune responses. Like many other viruses, HCV has evolved strategies to evade detection and elimination by NK cells. T cell defects observed in HCV infection may be a consequence of inhibition of NK:DC interactions. We propose a theoretical model for HCV persistence that places the NK cell at the center of HCV immune evasion strategies. While this model is only theoretical, it provides a plausible interpretation of many published observations and a useful working model to test the role of NK cells in HCV persistence. In conclusion, the role of innate immune cells and their regulation of antigen-specific responses by the initial innate response to the virus, in particular NK cells, may prove to be an informative and clinically relevant avenue of investigation.
Caroli's disease and orthotopic liver transplantation
Authors: Habib Shahid , Shakil Obaid , Couto Osvaldo F. , Demetris Anthony J. , Fung John J. , Marcos Amadeo , Chopra Kapil
Published: February 2006

Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver disease. Overall survival is better with liver transplantation and is comparable with the survival of recipients who undergo OLT for other etiologies of chronic liver disease. Survival was poor in patients with congenital hepatic fibrosis (Caroli's syndrome) and in those who had cholangitis at the time OLT.
Validation of cardiovascular risk scores in a liver transplant population
Authors: Guckelberger Olaf , Mutzke Florian , Glanemann Matthias , Neumann Ulf P. , Jonas Sven , Neuhaus Ruth , Neuhaus Peter , Langrehr Jan M.
Published: February 2006

Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (

P

< 0.001), gender (

P

= 0.002), body mass index (

P

= 0.018), cholesterol (

P

= 0.044), creatinine (

P

= 0.006), diabetes mellitus (

P

= 0.017), glucose (0.006), and systolic blood pressure (

P

= 0.043), but not cyclosporine A (

P

= 0.743), tacrolimus (

P

= 0.870), or steroid medication (

P

= 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of prospective intervention trials.
“Hepar divisum”– as a rare donor complication after intraoperative mortality of the recipient of an intended living donor liver transplantation
Authors: Nadalin Silvio , Malagó Massimo , Testa Giuliano , Schaffer Randolph , Sotiropoulos Georgios C. , Frilling Andrea , Broelsch Christoph E.
Published: February 2006

In this study, we present our experience with 4 healthy donors having the rare condition of “hepar divisum” after the intraoperative death of the recipient of an intended right adult living donor liver transplantation (LDLT). The study included 4 donors and 4 intended right LDLT recipients affected by neuroendocrine tumor (n = 2), hepatocellular carcinoma (n = 1), and cryptogenic cirrhosis (n = 1). All 4 recipients died intraoperatively. At the time of recipient death, the dissection of the donor liver parenchyma was complete, the vessels intact, and the hepatic duct(s) already divided. In each case, reconstruction of the donor biliary tract was performed: hepaticojejunostomy (HJ) in 2 cases, each with 3 ducts, and duct-to-duct anastomosis in 2. Of the donors receiving the HJ, 1 had a cut surface bile leak and the other experienced an anastomotic leak, treated by percutaneous drainage and reoperation, respectively. The latter patient experienced recurrent HJ stenosis at 44 months and 50 months after the operation and was treated by percutaneous balloon dilatation. One duct-to-duct reconstruction was complicated by early stenosis (postoperative day 6) and treated with endoscopic stenting. In conclusion, in the case of intraoperative death of the recipient of an intended LDLT, when the parenchyma and the hepatic duct of the donor have already been divided, the options are completion of the donor hepatectomy or the status of “fegatum divisum” with reconstruction of biliary tract. The high incidence of biliary complication, however, is of concern. When more than 1 hepatic duct is present, the donor hepatectomy should be completed and the graft reallocated according to the policy of the transplant institution.
Interventional radiology in liver transplantation
Authors: Amesur Nikhil B. , Zajko Albert B.
Published: February 2006

Improvements in surgical technique, advances in the field of immunosuppresion and the early diagnosis and treatment of complications related to liver transplantation have all led to prolonged survival after liver transplantation. In particular, advances in diagnostic and interventional radiology have allowed the Interventional Radiologist, as part of the transplant team, to intervene early in patients presenting with complications related to organ transplant with resultant increase in graft and patient survival. Such interventions are often achieved using minimally invasive percutaneous endovascular techniques. Herein we present an overview of some of these diagnostic and therapeutic approaches in the treatment and management of patients before and after liver transplantation.
Synthesis of Novel Monomers and Copolymers from 1‐Vinylpyrrolidin‐2‐one: Attractive Materials for Drug Delivery Systems?
Authors: Engström Jonas U. A. , Lindgren Lars J. , Helgee Bertil
Published: February 2006

Summary: Polyvinylpyrrolidone (PVP) is a synthetic, non‐toxic, water‐soluble polymer commonly used in a wide range of applications including several pharmaceutical applications. One example of an important application is the controlled release and delivery of therapeutic agents into sites of inflammation or tumours. However, PVP lacks reactive groups, which limits the possibility of adding new functions to the polymer in order to modify its physical and chemical properties. Furthermore, large differences in radical reactivity between 1‐vinylpyrrolidin‐2‐one (NVP) and most other monomers lead to compositional drift during copolymerization. This complicates the introduction of reactive groups into the polymer using this method. Monomers that are derivatives of NVP itself are expected to show smaller differences in radical reactivity and therefore provide a way of preparing PVP with adjustable properties. Here we present the synthesis of five NVP‐based monomers and their use in the preparation of functional PVP with adjustable properties in terms of solubility, loading of functional groups, and molar mass. The results show the possibility of tailoring PVP for different biomedical applications e.g. drug delivery systems.

Copolymers from 1‐vinylpyrrolidin‐2‐one.

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Copolymers from 1‐vinylpyrrolidin‐2‐one.
Synthesis and Micellization Properties of Novel Symmetrical Poly(ε‐caprolactone‐b‐[R,S] β‐malic acid‐b‐ε‐caprolactone) Triblock Copolymers
Authors: Coulembier Olivier , Degée Philippe , Dubois Philippe
Published: February 2006

Summary: A four‐step strategy to synthesize well‐defined amphiphilic poly(ε‐caprolactone‐b‐[R,S] β‐malic acid‐b‐ε‐caprolactone) triblock copolymers [P(CL‐b‐MLA‐b‐CL)], which combines the anionic polymerization of [R,S] benzyl β‐malolactonate (MLABz), and the coordination‐insertion ring‐opening polymerization (ROP) of ε‐caprolactone (CL), followed by the selective removal of benzyloxy protective groups of the central poly(malolactonate) block is described. The first step involves MLABz initiated by potassium 11‐hydroxydodecanoate in the presence of 18‐crown‐6 ether. This step was carried out at 0 °C with an initial monomer concentration of 0.2 mol · L−1 in order to limit the occurrence of undesirable transfer and termination reactions by proton abstraction. After selective reduction of the carboxylic acid end‐group of the resulting α‐hydroxy, ω‐carboxylic poly([R,S] benzyl β‐malolactonate) leading to an α,ω‐dihydroxy PMLABz, the polymerization of CL was initiated by each hydroxyl end‐groups previously activated by AlEt3. Finally, after catalytic hydrogenation of the benzyl ester functions, the P(CL‐b‐MLA‐b‐CL) triblock copolymer was recovered and the amphiphilic character evidenced by UV spectroscopy. As demonstrated, the CMC of these new P(CL‐b‐MLA‐b‐CL) triblock copolymer is higher by one order of magnitude than that of a P(MLA‐b‐CL) diblock copolymer of similar composition.

Concentration dependence of pyrene I338/I335 intensitiy ratio for P(MLA‐b‐CL) diblock and P(CL‐b‐MLA‐b‐CL) triblock copolymers in water.

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Concentration dependence of pyrene I338/I335 intensitiy ratio for P(MLA‐b‐CL) diblock and P(CL‐b‐MLA‐b‐CL) triblock copolymers in water.
Cover Picture: Macromol. Rapid Commun. 5/2006
Authors: Yamamoto Takakazu , Watanabe Shoutaro , Fukumoto Hiroki , Sato Masaru , Tanaka Tsuyoshi
Published: February 2006

Cover: An alternating copolymer between 2‐alkylamino‐1,3,5‐triazine and thiophene was soluble in organic solvents and transparent in most part of the visible region. The polymer showed time‐of‐flight electron drift mobility of 2.0 × 10−4 cm2 · V−1 · s−1. Because of the electronic and optical properties, the polymer is expected to be a useful material for photo devices such as photocopy, photovoltaic cell, and EL. Further details can be found in the Communication by T. Yamamoto,* S. Watanabe, H. Fukumoto, M. Sato, and T. Tanaka on page 317.
Gonadotropins affect Oct‐4 gene expression during mouse oocyte growth
Authors: Monti Manuela , Garagna Silvia , Redi CarloAlberto , Zuccotti Maurizio
Published: February 2006

The transcription factor Oct‐4 is required for the maintenance of stem cells pluripotency and is involved in the regulation of the expression of a number of developmental genes. Oct‐4 is also expressed in the female gamete during folliculogenesis, but the role it plays is largely unknown. Its upstream and promoter regions have some characteristic features that make this gene a possible target of hormonal regulation. To further our understanding of Oct‐4 gene expression during oocyte growth, we tested whether changes to the hormonal milieu of the ovary may affect its transcription. Using a semi‐quantitative single‐cell‐sensitive reverse transcription‐polymerase chain reaction (RT‐PCR) assay, we investigated the pattern of Oct‐4 expression during mouse oocyte growth in females intraperitoneally injected with pregnant mare serum gonadotropin (PMSG) alone or PMSG followed by human chorionic gonadotropin (hCG). The results of this study show that gonadotropins induced two major increases in Oct‐4 expression during folliculogenesis: (1) 48 hr after PMSG injection, in oocytes isolated from primordial follicles; and (2) following a surge of hCG, in preovulatory antral oocytes. These results suggest a potential twofold role for this gene in the recruitment of oocytes for initiating growth and in the selection of oocytes for ovulation. Also, they may contribute to our knowledge of the molecular bases of oocyte growth, meiosis resumption, and acquisition of a developmental competence. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
The murine Dnali1 gene encodes a flagellar protein that interacts with the cytoplasmic dynein heavy chain 1
Authors: Rashid Sajid , Breckle Rolf , Hupe Mike , Geisler Stephanie , Doerwald Nadine , Neesen Juergen
Published: February 2006

Axonemal dyneins are large motor protein complexes generating the force for the movement of eukaryotic cilia and flagella. Disruption of axonemal dynein function leads to loss of ciliary motility and can result in male infertility or lateralization defects. Here, we report the molecular analysis of a murine gene encoding the dynein axonemal light intermediate chain Dnali1. The Dnali1 gene is localized on chromosome 4 and consists of six exons. It is predominantly expressed within the testis but at a lower level Dnali1 transcripts were also observed in different murine tissues, which exhibit cilia. Two transcript variants were detected, generated by the usage of two alternative polyadenylation signals within exon 6. Antibodies were raised against a GST–Dnali1 fusion protein and used to localize Dnali1 within differentiating male germ cells. Dnali1 is strongly expressed in spermatids but was also detected in spermatocytes. Moreover, the Dnali1 protein was localized in cilia of the trachea as well as in flagella of mature sperm supporting its function as an axonemal dynein. To identify putative Dnali1 interacting polypeptides, a yeast two‐hybrid approach was performed using a murine testicular cDNA library. By this assay, the C‐terminal part of the cytoplasmic dynein heavy chain 1 was identified as a putative interacting polypeptide of Dnali1. The interaction between the axonemal and the cytoplasmic dynein fragments was proven by co‐immuno and co‐localization experiments. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly‐L‐lysine and a starburst dendrimer
Authors: McMahon Michael T. , Gilad Assaf A. , Zhou Jinyuan , Sun Phillip Z. , Bulte Jeff W. M. , van Zijl Peter C. M.
Published: February 2006

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH‐dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI‐compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly‐L‐lysine (PLL) and a generation‐5 polyamidoamine dendrimer (SPD‐5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH‐calibration curve of the agents consisting of contributions from spontaneous (k0) acid catalyzed (ka), and base catalyzed (kb) exchange rate constants. These constants were k0 = 68.9 Hz, ka = 1.21 Hz, kb = 1.92 × 109 Hz, and k0 = 106.4 Hz, ka = 25.8 Hz, kb = 5.45 × 108 Hz for PLL and SPD‐5, respectively, showing the expected predominance of base‐catalyzed exchange for these amide protons. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Hepatic lipid accumulation in healthy subjects: A comparative study using spectral fat‐selective MRI and volume‐localized 1H‐MR spectroscopy
Authors: Machann Jürgen , Thamer Claus , Schnoedt Birgit , Stefan Norbert , Haring Hans‐Ulrich , Claussen Claus D. , Fritsche Andreas , Schick Fritz
Published: February 2006

Fat‐selective MRI was applied to assess the amount and spatial distribution of hepatic lipids (HL) in healthy subjects. The results were compared with those obtained by localized 1H‐MR spectroscopy (MRS). Ninety subjects (23–63 years old) underwent single‐slice fat‐selective MRI with spatial‐spectral excitation and volume‐localized spectroscopy at 1.5 T. HLs were analyzed in ventral and dorsal regions of interest (ROIs) of the liver in fat‐selective images. Spectra were evaluated using the integral signal of methylene and methyl signals. The fat‐selective images showed smooth and homogeneous distribution of HL over the entire cross section of the liver. There was, however, a marked interindividual variability in the amount of HL. MRS revealed a lipid signal fraction between 0.5% and 39.3%. The fat content in the ROIs in images correlated well with the spectroscopic results (r ≥ 0.95). Both techniques provide sufficient sensitivity for a reliable and quantitative assessment of liver steatosis in subjects without liver disease. 1H‐MRS has a higher sensitivity compared to MRI, especially for small amounts of HL, which may be of interest for metabolic interventions. Fat‐selective images provide more spatial information about fat distribution, which makes this technique suitable for clinical imaging of patients with liver disease. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Novel 1H NMR approach to quantitative tissue oximetry using hexamethyldisiloxane
Authors: Kodibagkar Vikram D. , Cui Weina , Merritt Matthew E. , Mason Ralph P.
Published: February 2006

19F NMR spin‐lattice relaxometry of hexafluorobenzene (HFB) has been shown to be a highly sensitive indicator of tumor oxygenation. In this study hexamethyldisiloxane (HMDSO) was identified as a proton NMR analog, and its potential as a probe for investigating dynamic changes in tissue oxygen tension (pO2) was evaluated. HMDSO has a single proton resonance (δ= –0.3 ppm) and the spin‐lattice relaxation rate, Rl (= 1/T1) exhibits a linear dependence on pO2: R1 (s–1) = 0.1126 + 0.0013* pO2 (torr) at 37°C. To demonstrate application in vivo, HMDSO was administered into healthy rat thigh muscle (100 μl) and tumors (50 μl). Local pO2 was determined by using pulse‐burst saturation recovery (PBSR) 1H NMR spectroscopy to assess R1. Water and fat signals were effectively suppressed by frequency‐selective excitation of the HMDSO resonance. Rat thigh muscle had a mean baseline pO2 of 35 ± 11 torr, with a typical stability of ±3 torr over 20 min, when the rats breathed air. Altering the inhaled gas to oxygen produced a significant increase in pO2 to 100–200 torr. In tumors, altering the inspired gas also produced significant (albeit generally smaller) changes. This new pO2 reporter molecule offers a potentially valuable new tool for investigating pO2 in vivo. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.