bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiotherapy combined with transarterial infusion chemotherapy and concurrent infusion of a vasoconstrictor agent for nonresectable advanced hepatic hilar duct carcinoma
Authors: Matsumoto Shunro , Kiyosue Hiro , Komatsu Eiji , Wakisaka Masaki , Tomonari Kenichiro , Hori Yuzo , Matsumoto Akira , Mori Hiromu
Published: April 2004

BACKGROUND

The treatment of patients with advanced hepatic hilar duct carcinoma is a challenging problem. The current study was performed to evaluate the outcome of patients with advanced hepatic hilar duct carcinoma who received external beam radiotherapy (EBRT) combined with transarterial chemotherapy and infusion of a vasoconstrictor.

METHODS

Between April 1993 and December 2002, 23 patients with histopathologically confirmed hilar duct carcinoma entered the study. The median total dose of EBRT was 41.4 grays (Gy). Transarterial chemotherapy was performed twice during EBRT. It was comprised of an infusion of a cocktail of 20 mg of epirubicin, 10 mg of mitomycin C, and 500 mg of 5‐fluorouracil and was administered 1 minute after injection of epinephrine via a catheter introduced in the hepatic arteries. After the combined treatment, the patients underwent biliary endoprosthesis after evaluation of the initial response to treatment by percutaneous transhepatic cholangiography (PTC). The initial responses based on PTC were classified into four categories: CR, no stenosis; PR, relief of stenosis/obstruction; NC, no change; and PD, progressive stenosis/obstruction. The outcome parameters were survival rates and time, as well as frequency and type of complications.

RESULTS

Excluding 1 patient who discontinued the treatment, the initial responses of 22 patients were 1 CR (5%), 8 PR (36%), 11 NC (50%), and 2 PD (9%). The response rate was 41%. The overall survival rates at 1 year, 2 years, and 3 years after treatment were 59%, 36%, and 18%, respectively.

CONCLUSIONS

The combination of radiotherapy, transarterial infusion chemotherapy, and concurrent infusion of a vasoconstrictor can be delivered safely with good efficacy for patients withadvanced hilar duct carcinoma. Cancer 2004. © 2004 American Cancer Society.
Retroperitoneal soft tissue sarcomas
Authors: Gronchi Alessandro , Casali Paolo G. , Fiore Marco , Mariani Luigi , Lo Vullo Salvatore , Bertulli Rossella , Colecchia Maurizio , Lozza Laura , Olmi Patrizia , Santinami Mario , Rosai Juan
Published: April 2004

BACKGROUND

The objective of this study was to assess long‐term prognosis and patterns of failure in patients with retroperitoneal soft tissue sarcoma who underwent surgery with curative intent at a single institution. Several series of patients with retroperitoneal sarcoma were reported, providing widely variable data regarding local and distant failure.

METHODS

Overall, 167 consecutive patients who underwent surgery for retroperitoneal soft tissue sarcoma over a 20 year span at a single referral center were reviewed retrospectively. Eighty‐two patients presented with primary disease, whereas 85 patients had recurrent locoregional tumors. Surgical resection was considered macroscopically complete in 147 of 167 patients (88%).

RESULTS

Overall survival at 10 years after definitive surgery was approximately 27%, and the disease‐free survival was approximately 16%. Only a minority of patients developed distant metastases. The risk of recurrence was correlated with whether patients underwent surgery for primary disease or for recurrent disease; the 10 year disease‐free survival rate was 27% in the former group and 4.6% in the latter group. Histotype and malignancy grade were other prognostic factors, with the former found to be predictive of the pattern of failure and the latter predictive of overall survival.

CONCLUSIONS

Local recurrence after primary surgery and high‐grade malignancy were associated with the worst survival. Histologic subtype appeared to influence the pattern of recurrence, which mainly was local for patients with liposarcoma but was both local and distant for patients with the other histotypes. Cancer 2004. © 2004 American Cancer Society.
Diversity matters: Unique populations of women and breast cancer screening
Authors: Magai Carol , Consedine Nathan , Conway Francine , Neugut Alfred , Culver Clayton
Published: April 2004

BACKGROUND

Ethnic differences in breast cancer screening behaviors are well established. However, there is a lack of understanding regarding exactly what causes these differences and which characteristics in low‐screening populations should be targeted in an effort to modify screening behavior.

METHODS

Stratified cluster sampling was used to recruit 1364 women (ages 50–70 years) from 6 ethnic groups: African‐American women; U.S.‐born white women; English‐speaking Caribbean, Haitian, and Dominican women; and immigrant Eastern‐European women. In interviews, respondents provided information concerning demographic and structural variables related to mammogram utilization (age, education, income, marital status, physician recommendation, access, and insurance) and a set of cognitive variables (fatalism, perception of personal risk, health beliefs concerning cancer) and socioemotional variables (stress, cancer worry, embarrassment, and pain).

RESULTS

For data analysis, the authors used a 2‐step logistic regression with frequency of mammograms over a 10‐year period (≤ 4 mammograms over 10 years or ≥ 5 mammograms over 10 years) as a dependent variable. U.S.‐born African‐American women and Dominican women were screened as frequently as European‐American women, but the remaining minority groups were screened with less frequency. With one exception, ethnicity ceased to predict screening frequency once cognitive and emotional variables were controlled.

CONCLUSIONS

Although women from clearly operationalized ethnic groups continue to screen at rates substantially below those of the majority groups, these differences appear to be explained substantially by differences in psychologic variables. This is encouraging because, rather than targeting culture for intervention, variables can be targeted that are amenable to change, such as emotions and beliefs. Cancer 2004. © 2004 American Cancer Society.
Comparison between non‐probabilistic interval analysis method and probabilistic approach in static response problem of structures with uncertain‐but‐bounded parameters
Authors: Qiu Zhiping , Ma Yi , Wang Xiaojun
Published: April 2004

The uncertainty present in many practical engineering analysis and design problems can be modelled using probabilistic or non‐probabilistic interval analysis methods. One motivation for using non‐probabilistic interval analysis models rather than probabilistic models for uncertain variables is the general dearth of information in characterizing the uncertainties. Non‐probabilistic interval analysis methods are less information‐intensive than probabilistic models, since no density information is required. Instead of conventional optimization studies, where the minimum possible response is sought, here an uncertainty model is developed as an anti‐optimization problem of finding the least favourable response and the most favourable response under the constraints within the set‐theoretical description. Non‐probabilistic interval analysis methods have been used for dealing with uncertain phenomena in a wide range of engineering applications. This paper is concerned with the problem of comparison between the non‐probabilistic interval analysis method and the probabilistic approach in the static response problem of structures with uncertain‐but‐bounded parameters from mathematical proofs and numerical calculations. The results show that under the condition of the interval vector of the uncertain parameters determined from the probabilistic and statistical information, the width of the static displacement obtained by the non‐probabilistic interval analysis method is larger than that by the probabilistic approach for structures with uncertain‐but‐bounded structural parameters. This is just the result that we expect, since according to the definition of probabilistic theory and interval mathematics, the region determined by the non‐probabilistic interval analysis method should contain one predicted by the probabilistic approach. Copyright © 2004 John Wiley & Sons, Ltd.
Method to solve the non‐linear systems of equations for steady gradually varied flow in open channel network
Authors: Szymkiewicz R. , Szymkiewicz A.
Published: April 2004

The paper concerns the solution of non‐linear system of equations arising while solving a steady gradually varied flow in an open channel network. To reduce the dimensions of final system the depths at each cross‐section and the discharge at each branch are considered as unknowns. Newton and Picard iteration can suffer from non‐convergent saw‐tooth errors. An approach to improve and consequently to ensure the convergence of the Picard method is proposed. Using the average from two successive iterations suppresses the saw‐teeth and gives a robust convergent iteration method to solve a steady gradually varied flow in any type of open channel network. The improvement in performance is confirmed by numerical tests. Copyright © 2004 John Wiley & Sons, Ltd.
On the residue calculus evaluation of the 3‐D anisotropic elastic green's function
Authors: Phan A.‐V. , Gray L. J. , Kaplan T.
Published: April 2004

An algorithm based upon the residue calculus for computing three‐dimensional anisotropic elastic Green's function and its derivatives has been presented in Sales and Gray (Comput. Structures 1998; 69:247–254). It has been shown that the algorithm runs three to four times faster than the standard Wilson–Cruse interpolation scheme. However, the main concern of the Sales–Gray algorithm is its numerical instability that could lead to significant errors due to the existence of multiple poles of the residue. This paper proposes a remedy for the problem by adding the capability to evaluate the Green's function in case of multiple poles of the residue. Further, an improved numerical implementation based on the use of double‐subscript‐notation elastic constants in determining the Christoffel tensor is also at issue. Copyright © 2004 John Wiley & Sons, Ltd.
Quantification of temporary and permanent subpopulations of bull sperm by an optimized SYBR‐14/propidium iodide assay
Authors: Grundler Werner , Dirscherl Peter , Beisker Wolfgang , Weber Frank , Stolla Rudolf , Bollwein Heinrich
Published: April 2004

Background

The quality of bull sperm is a key factor in the field of controlled reproduction. Viability‐testing is an important aspect of sperm quality definition, especially after cryopreservation where multiple factors such as handling, freeze‐thaw cycle, and preservation media, have an impact on the metabolic and functional state of sperm cells.

Methods

We investigated the commonly used SYBR‐14/propidium iodide (PI) assay to obtain functional information about sperm‐dye and dye‐dye interactions. After optimizing filter settings, dye concentrations and incubation times we used these dyes for an interruption free flow cytometric kinetic analysis of a mixture of viable and dead bovine sperm.

Results

For the sensitivity of this method and the separation of the different cellular subpopulations fluorescence quenching of SYBR‐14 by PI is mainly responsible. Together with a spectral overlap of the two emission spectra of about 5%, even for a wavelength greater than 700 nm, this quenching effect has to be taken into account for a quantitative understanding of the observed fluorescence intensity signals. The fraction of a temporary “intermediate” population to be observed between the viable and dead cells in an SYBR‐14/PI‐dot‐plot diagram becomes greater after stress on the sperm cells caused by cryopreservation. The temporary fraction of “intermediate” cells is maximal at about 6 min after staining and disappears after about 15 min by shifting towards the dead sperm population. The estimation of this “intermediate” population may be a good indicator for handling and storage induced detrimental effects on bovine sperm cells.

Conclusion

The SYBR‐14/PI assay is a fast, reliable and sensitive method to assess the membrane integrity of bull sperm and to separate viable, dead, and “intermediate” sperm subpopulations. © 2004 Wiley‐Liss, Inc.
Flow cytometric analysis of the oxidative status of normal and thalassemic red blood cells
Authors: Amer Johnny , Goldfarb Ada , Fibach Eitan
Published: April 2004

Background

The oxidative status of cells has been shown to modulate various cell functions and be involved in physiological and pathological conditions, including hereditary chronic anemias, such as thalassemia. It is maintained by the balance between oxidants, such as reactive oxygen species (ROS), and antioxidants, such as reduced glutathione (GSH).

Methods

We studied peripheral RBC derived from normal and thalassemic donors. Flow cytometric methods were used to measure (1) generation of ROS; (2) the content of reduced GSH; and (3) peroxidation of membrane lipids as an indication of membrane damage.

Results

ROS and lipid peroxidation were found to be higher, and GSH lower, in thalassemic RBC compared with normal RBC, both at baseline as well as following oxidative stress, such as exposure to hydrogen peroxide. To simulate a state of iron overload, normal RBC were exposed to extracellular ferric ammonium citrate or hemin, or their Hb was denatured by phenylhydrazine. All these treatments increased ROS and lipid peroxidation and decreased GSH. These effects were reversed by N‐acetyl cysteine, a known ROS scavenger.

Conclusions

Flow cytometry can be useful for measuring oxidative stress and its effects on RBC in various diseases and for studying various chemical agents as antioxidants. © 2004 Wiley‐Liss, Inc.
The incidence of congestive heart failure associated with antidiabetic therapies
Authors: Nichols Gregory A. , Koro Carol E. , Gullion Christina M. , Ephross Sara A. , Brown Jonathan B.
Published: April 2004

Background

Increased risk for CHF in persons with type 2 diabetes is well established. Our objectives were to estimate the CHF risk associated with specific therapies for diabetes and to determine the differences in incidence rates of CHF associated with adding various antidiabetic agents.

Methods

Subjects were members of the Kaiser Permanente Northwest (KPNW) diabetes registry as of 1 January 1998, with no prior history of CHF (n = 8063). We identified their therapy as of that date and then defined the start of the subject study period as the date when their drug regimen changed, either by switching to or by adding another antidiabetic drug. We defined the new therapy as the index therapy and the date of initiating the new therapy as the index date. Follow‐up on the patients was done until the index therapy was discontinued or changed, or until 31 December 2002, whichever came earlier. We calculated the incidence rate of CHF in patients on various therapeutic regimens adjusting for age, gender, diabetes duration, existing ischemic heart disease, hypertension, renal insufficiency and glycemic control (HbA1c).

Results

CHF incidence rates were highest in index therapy categories that included insulin and lowest in regimens that included metformin. When insulin was added to an initial therapy, CHF incidence was increased 2.33 times (p < 0.0001) and 2.66 times (p < 0.0001) compared to the addition of sulphonylurea or metformin respectively.

Conclusions

Our findings support the theory that elevated serum insulin levels promote the development of cardiac disease. Consistent with the UKPDS, metformin may offer some protection from incident CHF relative to sulphonylurea or insulin. Copyright © 2004 John Wiley & Sons, Ltd.
Determination of glycated hemoglobin in clinically silent hemoglobin variants
Authors: Schnedl Wolfgang J. , Lahousen Theresa , Lang Thomas , Lipp Rainer W. , Yonehara Satoshi , Fukunaga Satoshi , Imai Toshihiro , Little Randie R.
Published: April 2004

Background

Evaluation of glycated hemoglobin determination methods in patients with clinically silent hemoglobin variants.

Methods

HbA1c results were determined with various methods, including a new enzymatic assay, a boronate affinity HPLC, immunoassays and ion‐exchange HPLC in patients with the clinically silent hemoglobin variants Hb Graz, Hb Sherwood Forest, Hb D and Hb O Padova.

Results

The effect of hemoglobin variants on glycated hemoglobin determination was method‐dependent. The enzymatic and boronate affinity HPLC method did not interfere with any of the variants evaluated. In contrast, Hb Graz interfered with all immunoassay and ion‐exchange HPLC methods evaluated. The Tosoh ion‐exchange HPLC method HLC‐723 did not detect the late migrating Hb O Padova in the chromatogram, but this hemoglobin variant still interfered causing artificially low HbA1c results.

Conclusions

Our study underscores the need for clinical laboratories and physicians to be aware of the limitations of their HbA1c assay methods as well as the importance of visual inspection of ion‐exchange chromatograms to detect abnormalities caused by the hemoglobin variants. Samples with clinically silent Hb variants should be analyzed by a second method with a different assay principle, preferably a boronate affinity HPLC or an enzymatic assay. Copyright © 2004 John Wiley & Sons, Ltd.
Crosstalk fault testing by the built‐in self‐test method with test points and phase shifters
Authors: Shimizu Kazuya , Shirai Takanori , Itazaki Noriyoshi , Kinoshita Kozo
Published: April 2004

With the progressive decreases in size and increases in the speed of VLSI, guaranteeing signal integrity has become important. This paper focuses on crosstalk as a factor responsible for the violation of signal integrity and proposes a method of testing for crosstalk faults. The built‐in self‐test (BIST) method, which can detect crosstalk faults by using an M‐sequence of a linear feedback shift register (LFSR), has been proposed. But since the output of the LFSR is used unaltered as a random test pattern, an insufficient number of crosstalk pulses is excited and some faults escape detection. We therefore propose the use of a new testing circuit which increases the number of crosstalk pulses that are excited and makes possible the detection of faults that were previously undetectable. The new testing circuit uses test points and phase shifter circuits which can output sequences that have arbitrary delays from the M‐sequence. In addition, by changing the simulation method, it also becomes applicable to large‐scale circuits for which such simulations could not be used in the past. We evaluate the detection rate and area overhead for several benchmark circuits and show that the method is effective in detecting crosstalk faults. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(10): 54–65, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20108
View generation for a virtual camera using multiple depth maps
Authors: Hiruma Kaori , Okimura Takayuki , Uehira Kazutake
Published: April 2004

This paper proposes a method of generation of images taken from a virtual viewpoint, based on depth information on the object when viewed from multiple positions. First, the depth map from a viewpoint is converted to the depth map of the object as viewed from a virtual point. Then, based on the depth map from another viewpoint, the occlusion area of the virtual viewpoint depth map is complemented and the depth value is corrected. By appropriate use of real images through interpolation of depth values and smoothing, a virtual viewpoint image is generated. Applying the proposed method makes it possible to generate a virtual viewpoint image with less occlusion, even for a viewpoint deviating greatly from the actual camera position. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(10): 81–88, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20110
Structural Properties of Bis(hexacarbonyldicobalt) Complexes with Heteroatoms Next to the Former Triple Bonds − A Contribution to the Mechanism of the Pauson−Khand Reaction
Authors: Werz Daniel B. , Schulte J. Hilko , Rausch Bernhard J. , Gleiter Rolf , Rominger Frank
Published: April 2004

The bis(hexacarbonyldicobalt) complexes of cyclic diynes with sila‐, thia‐ and selena‐substituted acetylene units have been isolated. The structural features of these complexes have been elucidated by means of X‐ray diffraction analyses on single crystals. In three cases (24′, 25′ and 29′) the X‐ray investigations show bis(pentacarbonyldicobalt) complexes instead of bis(hexacarbonyldicobalt) ones. Their empty coordination sites are each occupied by divalent chalcogen moieties from the opposite side of the molecule affording distorted C2Co2 cores. These results corroborate the possibility of intramolecular activation in Pauson−Khand reactions of chalcogen‐containing substrates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Controlled Access to Mixed‐Metal Pyridazine‐Linked Cryptates
Authors: Ronson Tanya K. , Nelson Jane , Jameson Geoffrey B. , Jeffery John C. , Brooker Sally
Published: April 2004

The pyridazine‐linked cryptand L [formed by the 3+2 condensation of 3,6‐diformylpyridazine with tris(2‐aminoethyl)amine (tren)] has been used to generate a series of heterodinuclear cryptates by a one‐pot two‐step method. The cryptates [MnIICuIL](ClO4)2(BF4), [FeIICuIL](BF4)3·CH3CN and [NiIICuIL](BF4)3·H2O have been structurally characterized, with elemental analyses and mass spectroscopic data providing further evidence of their heterodinuclear nature. The synthesis, structures and characterisation of the corresponding mononuclear cryptates [MIIL](X)2 (M = Mn, Fe, Ni, X = BF4− or ClO4−) are also reported, along with the synthesis and characterisation of the homodinuclear dizinc(II) and disodium(I) cryptates, [Zn2L](ClO4)4 and [Na2L](CF3SO3)2. Electrochemical studies on the heterodinuclear cryptates in CH3CN indicate that the presence of the divalent cation influences the electrochemical potential and reversibility of the CuI → CuII oxidation with the redox potential of the CuI/CuII couple being inversely correlated with the distance between the two metal ions in the solid state as determined by X‐ray crystallography. The previously synthesised [CoIICuIL](BF4)3 is an exception to this trend, probably due to oxidation of the CoII ion prior to that of the CuI ion. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of a Novel Cyclic Chlorophyll Hetero‐Dyad as a Model Compound for Stacked Chlorophylls Found in Photosynthetic Systems
Authors: Kosaka Nobuo , Tamiaki Hitoshi
Published: April 2004

A covalently doubly linked cyclic chlorophyll hetero‐dyad was stereospecifically prepared as a model for naturally stacked chlorophyll suprastructures. In the synthetic dyad, two composite macrocycles are situated very close to each other such that the Qy transition dipole moments intramolecularly interact to give intense circular dichroism peaks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Thoughts on the 25th anniversary of bulimia nervosa
Authors: Russell G. F. M.
Published: April 2004

My original article on bulimia nervosa appeared in the August 1979 issue of Psychological Medicine. It is timely to examine whether the description of this new disorder and the formulated diagnostic criteria have stood the test of time. A similar question is whether it was right to describe the new syndrome as an ominous variant of anorexia nervosa. The answers to these questions should really be given by other investigators. My own view is that the main clinical description and the diagnostic criteria of bulimia nervosa have proved reasonably robust, as has its close relationship to anorexia nervosa. On the other hand, my view about the ominous nature of bulimia nervosa was unduly pessimistic. The original description of bulimia nervosa had a significant impact on the clinical and scientific literature, which showed an accelerated growth during the 1980s, largely due to articles on bulimia and bulimia nervosa. The historical question ‘Is bulimia nervosa a new disorder?’ has hitherto been neglected. The evidence for answering this question in the affirmative is very strong and is derived from searches of the older psychiatric literature as well as more recent cohort studies which throw light on when the new syndrome burst from the blue upon modern society. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.
The influence of rock resistance on coastal morphology around Lord Howe Island, southwest Pacific
Authors: Dickson M. E. , Kennedy D. M. , Woodroffe C. D.
Published: April 2004

An Erratum has been published for this article in Earth Surface Processes and Landforms 27(7) 2004, 931.

Lord Howe Island, in the northern Tasman Sea, is a remnant of a much larger Late Miocene basaltic shield volcano. Much of the island's coastline is exposed to waves that have unlimited fetch, but a marked contrast is provided by a fringing coral reef and lagoon that very effectively attenuate wave energy along a portion of the western coastline. The geology of the island is varied, with hard and resistant basalt lavas, breccias and tuffs of intermediate resistance, and highly erodible eolianites. This variability provides an excellent opportunity to examine the inﬂuence of rock resistance on the development of the spectacular rock coast landforms that occur around the island. The hardness of rocks and the extent of weathering around the coastline were assessed using a Schmidt hammer, and statistical analysis was undertaken to remove outlying values. On all but one occasion, higher mean rebound values were returned from fresh surfaces than weathered surfaces, but only half of these differences were statistically signiﬁcant. Shore platforms with two distinct levels are juxtaposed along two stretches of coastline and Schmidt hammer results lend support to hypotheses that the raised surfaces may be inherited features. Relative rock resistance was assessed through a combination of Schmidt hammer data and measurements of joint density, and constrained on the basis of morphological data. This approach formed a basis for examining threshold conditions for sea‐cliff erosion at Lord Howe Island in the context of the distribution of resistant plunging cliffs and erosional shore platforms. Copyright © 2004 John Wiley & Sons, Ltd.
Method for using complete and incomplete trios to identify genes related to a quantitative trait
Authors: Kistner Emily O. , Weinberg Clarice R.
Published: April 2004

A number of tests for linkage and association with qualitative traits have been developed, with the most well‐known being the transmission/disequilibrium test (TDT). For quantitative traits, varying extensions of the TDT have been suggested. The quantitative trait approach we propose is based on extending the log‐linear model for case‐parent trio data (Weinberg et al. [1998] Am. J. Hum. Genet. 62:969–978). Like the log‐linear approach for qualitative traits, our proposed polytomous logistic approach for quantitative traits allows for population admixture by conditioning on parental genotypes. Compared to other methods, simulations demonstrate good power and robustness of the proposed test under various scenarios of the genotype effect, distribution of the quantitative trait, and population stratification. In addition, missing parental genotype data can be accommodated through an expectation‐maximization (EM) algorithm approach. The EM approach allows recovery of most of the lost power due to incomplete trios. Published 2004 Wiley‐Liss, Inc.
Reduced recruitment of motor association areas during bimanual coordination in concert pianists
Authors: Haslinger Bernhard , Erhard Peter , Altenmüller Eckart , Hennenlotter Andreas , Schwaiger Markus , Gräfin von Einsiedel Helga , Rummeny Ernst , Conrad Bastian , Ceballos‐Baumann Andrés O.
Published: April 2004

Bimanual motor coordination is essential for piano playing. The functional neuronal substrate for high‐level bimanual performance achieved by professional pianists is unclear. We compared professional pianists to musically naïve controls while carrying out in‐phase (mirror) and anti‐phase (parallel) bimanual sequential finger movements during functional magnetic resonance imaging (fMRI). This task corresponds to bimanually playing scales practiced daily by pianists from the beginning of piano playing. Musicians and controls showed significantly different functional activation patterns. When comparing performance of parallel movements to rest, musically naïve controls showed stronger activations than did pianists within a network including anterior cingulate cortex, right dorsal premotor cortex, both cerebellar hemispheres, and right basal ganglia. The direct comparison of bimanual parallel to mirror movements between both groups revealed stronger signal increases in controls within mesial premotor cortex (SMA), bilateral cerebellar hemispheres and vermis, bilateral prefrontal cortex, left ventral premotor cortex, right anterior insula, and right basal ganglia. These findings suggest increased efficiency of cortical and subcortical systems for bimanual movement control in musicians. This may be fundamental to achieve high‐level motor skills allowing the musician to focus on artistic aspects of musical performance. Hum. Brain Mapping 22:206–215, 2004. © 2004 Wiley‐Liss, Inc.
Recently primed CD8+ T cells entering the liver induce hepatocytes to interact with naïve CD8+ T cells in the mouse
Authors: Dikopoulos Nektarios , Wegenka Ursula , Kröger Andrea , Hauser Hansjörg , Schirmbeck Reinhold , Reimann Jörg
Published: April 2004

Large number of T cells traffic through the liver. In order to examine the effects of such traffic on the phenotype of hepatocytes, we vaccinated mice using DNA vaccines encoding antigens with MHC class I-binding epitopes. Small numbers of activated CD8+ T blasts (105-106/liver) changed the surface phenotype and cytokine expression profile of hepatocytes (HCs). HCs upregulate surface expression of major histocompatibility complex (MHC) class I molecules and CD1d but not MHC class II molecules Qa-1, CD80, CD86, CD54, or CD95; in addition, they expressed/secreted interleukin (IL)-10 and IL-4 but not IL-1, IL-6, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF), IL-4, or IL-27 (i.e., they acquire the HC* phenotype). HCs* (but not HCs) induced specific activation, proliferation, and IFN-γ, TNF, and IL-13 release of cocultured naïve CD8+ T cells. In contrast to the specific activation of naïve CD8+ T cells by dendritic cells (DCs), specific CD8+ T cell activation by HC* was not down-modulated by IFN-αβ. Only recently activated CD8+ T blasts (but not recently activated CD4+ T blasts or activated cells of the innate immune system, including natural killer T [NKT] cells) induced the HC* phenotype that is prominent from day 10 to day 20 postvaccination (i.e., time points at which peak numbers of recently primed CD8+ T blasts are found in the liver). In conclusion, recently activated CD8+ T blasts that enter the liver postimmunization in small numbers can transiently modulate the phenotype of HC, allowing them to activate naïve CD8+ T cells with unrelated specificities. (Hepatology 2004;39:1256-1266.)
Angiogenesis in chronic inflammatory liver disease
Authors: Medina Jesús , Arroyo Alicia G. , Sánchez-Madrid Francisco , Moreno-Otero Ricardo
Published: April 2004

Intrahepatic hypoxia may occur during the inflammatory and fibrotic processes that characterize several chronic liver diseases of viral and autoimmune origin. As a consequence, new vascular structures are formed to provide oxygen and nutrients. Angiogenesis involves a tightly regulated network of cellular and molecular mechanisms that result in the formation of functional vessels. Of particular importance are growth factors, molecules involved in matrix remodeling and cell migration, and vessel maturation—related factors. In recent years, a number of studies have examined the expression and function of many pro- and antiangiogenic molecules in the setting of nontumoral chronic liver diseases and liver regeneration. This review examines the potential pathogenetic role of angiogenesis in the context of viral hepatitis, cirrhosis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver disease. The future perspectives for research in this field are outlined. (Hepatology 2004;39:1185-1195.)
Preparation of the Enantiomerically Enriched Isomers of the Odorous Cyclic Ethers Clarycet ®, Florol ®, and Rhubafuran ® by Enzymatic Catalysis
Authors: Abate Agnese , Brenna Elisabetta , Fronza Giovanni , Fuganti Claudio , Gatti Francesco G. , Serra Stefano , Zardoni Enrica
Published: April 2004

All the enantiomerically enriched stereoisomers of Clarycet ® (1), Florol ® (2), and Rhubafuran ® (3) were prepared by biocatalysis routes. Their absolute configurations were established, and their olfactory properties were fully evaluated.
Four New Phenolic Compounds from Curculigo crassifolia (Hypoxidaceae)
Authors: Li Ning , Chen Ji‐Jun , Zhou Jun
Published: April 2004

Four new phenolic compounds, named crassifogenin A (1), crassifogenin B (2), crassifoside A (3), and crassifoside B (4), were isolated from the EtOH extract of the rhizomes of Curculigo crassifolia, and based on the chemical transformation and modern spectroscopic experiments, including 2D‐NMR techniques (HMQC, HMBC, COSY, HMQC‐TOCSY, and NOE), their structures were elucidated as 2,5‐bis(3,4‐dihydroxyphenyl)furan‐3‐carbaldehyde (1), (3,4‐dihydroxyphenyl)(3,6,7‐trihydroxynaphthalen‐1‐yl)methanone (2), (3,4‐dihydroxyphenyl)[3‐(β‐D‐glucopyranosyloxy)‐6,7‐dihydroxynaphthalen‐1‐yl]methanone (3), and 1,2‐O‐{2‐(3,4‐dihydroxyphenyl)‐1‐[3‐(3,4‐dihydroxyphenyl)prop‐2‐ynyl]ethane‐1,2‐diyl}‐β‐D‐glucopyranose (4).
Synthesis of (±)‐Trinervitadiene‐2,3‐diol
Authors: Kato Tadahiro , Hoshikawa Masahiro
Published: April 2004

The first synthesis of trinervita‐1(15),8(19)‐dien‐2β,3α‐diol (2a) and its 2α‐isomer 2b, which have been isolated from termite soldiers, where they are used as defense chemicals, is documented starting from geranylgeranioic acid in 33 steps. The route for construction of the key intermediate of the trinervitane skeleton 8 has been developed previously (Scheme 1). Noteworthy features include the efficient construction of the trinervitane framework from the corresponding bicyclic 7(16)‐secotrinervitane skeleton and Me3SiCl (TMSCl)‐induced ring‐opening of tetrasubstituted epoxide to give the corresponding allyl alcohols (Scheme 7). The synthetic route developed in the present study seems applicable to the syntheses of other trinervitane‐type natural products.
Furo[2,3‐d]pyrimidines and Oxazolo[5,4‐d]pyrimidines as Inhibitors of Receptor Tyrosine Kinases (RTK)
Authors: Martin‐Kohler Andreas , Widmer Jörg , Bold Guido , Meyer Thomas , Séquin Urs , Traxler Peter
Published: April 2004

Receptor tyrosine kinases such as VEGFR2 (vascular endothelial growth factor receptor 2, KDR) or EGFR (epidermal growth factor receptor) play crucial roles in a variety of diseases, such as cancer. Recently, some pyrrolopyrimidines were shown to be potent EGFR inhibitors. Therefore, new types of oxazolo[5,4‐d]pyrimidines and furo[2,3‐d]pyrimidines were synthesized (Schemes 1 and 2). Appropriately substituted derivatives of these classes of compounds inhibited VEGFR2 and EGFR with IC50 values in the low nanomolar range (see Table). Generally, the furopyrimidines were somewhat more active than the oxazolopyrimidines. The best inhibitors, 20m, 20p, and 20r, had an IC50 of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2.
Five New Sesquiterpenoids from Parasenecio petasitoides
Authors: Zhang Hua , Liao Zhi‐Xin , Yue Jian‐Min
Published: April 2004

From the whole plants of Parasenecio petasitoides, five new sesquiterpenoids were isolated, (E,E)‐3α,9β‐dihydroxy‐6βH,11βH‐13‐norgermacra‐1(10),4‐dien‐11,6‐carbolactone (2), (E,E)‐2α,9β‐dihydroxy‐6βH,11βH‐13‐norgermacra‐1(10),4‐dien‐11,6‐carbolactone (3), (E,E)‐2α,9β‐dihydroxy‐6βH,11αH‐13‐norgermacra‐1(10),4‐dien‐11,6‐carbolactone (4), (E)‐15‐hydroxy‐2‐oxo‐6βH,11αH‐13‐norguaia‐3‐ene‐11,6‐carbolactone (7), and (E)‐11β,15‐dihydroxy‐2‐oxo‐6βH‐13‐norguaia‐3‐ene‐11,6‐carbolactone (8), together with three known compounds, deacetyl herbolide A (1), jacquilenin (5), and (E)‐15‐hydroxy‐2‐oxo‐6βH,11βH‐13‐norguaia‐3‐ene‐11,6‐carbolactone (6). The structures of these natural products were elucidated spectroscopically, especially by 1D‐ and 2D‐NMR techniques, in combination with high‐resolution mass spectroscopy.
Putting error bars on the Ab Initio theoretical estimates of the magnetic coupling constants: The parent compounds of superconducting cuprates as a case study
Authors: Muñoz D. , De Graaf C. , Illas F.
Published: April 2004

The influence of the basis set size and computational method in the calculation of the magnetic coupling constant J is evaluated using a series of cuprate superconductor parent compounds as a case study. The variational DDCI method and an iterative modification, the IDDCI method, are tested, as well as the perturbative CASPT2 method, with two different reference wave functions. Results show that the DDCI magnetic coupling constant is in rather good agreement with the experiment, although it shows a moderate basis set dependency. The IDDCI results are less dependent on the size of the basis set, but slightly overestimate the magnetic coupling constant. CASPT2 results are nearly independent of the chosen basis set. With a minimal active space values are obtained that are about 20% smaller than the DDCI results. The experimental coupling constant can be reproduced when an extended reference wave function is used. © 2004 Wiley Periodicals, Inc. J Comput Chem 10: 1234–1241, 2004
Human FGF‐1 gene transfer promotes the formation of collateral vessels and arterioles in ischemic muscles of hypercholesterolemic hamsters
Authors: Caron Alexis , Michelet Sandrine , Caron Anne , Sordello Sylvie , Ivanov Marie‐Agnès , Delaère Pia , Branellec Didier , Schwartz Bertrand , Emmanuel Florence
Published: April 2004

Background

Acidic fibroblast growth factor (FGF‐1) has been identified as a potent mitogen for vascular cells, inducing formation of mature blood vessels in vitro and in vivo and represents one of the most promising approaches for the treatment of ischemic cardiovascular diseases by gene therapy. Nevertheless, and most probably due to the few experimental models able to address the issue, no study has described the therapeutic effects of FGF‐1 gene transfer in subjects with peripheral arterial disease (PAD) exhibiting a clinically relevant cardiovascular pathology.

Methods

In order to assess the potency of FGF‐1 gene transfer for therapeutic angiogenesis in ischemic skeletal muscles displaying decreased gene expression levels and sustained impaired formation of collateral vessels and arterioles, we developed a model of PAD in hamsters with a background of hypercholesterolemia. Hamsters fed a cholesterol‐rich diet and subjected to hindlimb ischemia exhibit a sustained impaired angiogenic response, as evidenced by decreased angiographic score and histological quantification of arterioles in the ischemic muscles.

Results

In this model, we demonstrate that NV1FGF (a human FGF‐1 expression plasmid), given intramuscularly 14 days after induction of hindlimb ischemia, promoted the formation of both collateral vessels and arterioles 14 days after treatment (i.e. 28 days post‐ischemia).

Conclusions

Our data provide evidence that NV1FGF can reverse the cholesterol‐induced impairment of revascularization in a hamster model of hindlimb ischemia by promoting the growth of both collateral vessels and arterioles in ischemic muscles exhibiting significantly decreased levels of gene expression compared with control muscles. Therefore, this study underscores the relevance of NV1FGF gene therapy to overcome perfusion defects in patients with PAD. Copyright © 2004 John Wiley & Sons, Ltd.
Commuters and marauders: an examination of the spatial behaviour of serial criminals
Authors: Meaney Rebecca
Published: April 2004

The demographic characteristics of serial offenders that distinguish between the commuter and the marauder offence styles were examined. Proposed by Canter and Larkin (1993) these two styles represent competing models of criminal spatial behaviour under which the home base plays a role in offence site selection. Data on serial burglars, arsonists and sex offenders were extracted from the criminal records maintained by the NSW Police Service. The offence style of each offender's crime series was identified in order to relate the offence style to the demographic variables, and to examine the offender's first and last offences in a series. A commuter offence style was more likely to be adopted by burglars and generally by adult males. A marauding offence style was apparent in sex offenders and metropolitan based offenders. There was a progression in the distance travelled to offend across all crime types, as the last offence was located further from the home base by comparison with the first. These findings serve to validate the conceptual distinction between commuter and marauder offence styles. Several implications for further research are addressed. Copyright © 2004 John Wiley & Sons, Ltd.
Hepatitis B infection of the liver in chronic hepatitis C without detectable hepatitis B virus DNA in serum
Authors: Mariscal Luisa Fernanda , Rodríguez‐Iñigo Elena , Bartolomé Javier , Castillo Inmaculada , Ortiz‐Movilla Nuria , Navacerrada Cristina , Pardo Margarita , Pérez‐Mota Arturo , Graus Javier , Carreño Vicente
Published: April 2004

Hepatitis B virus (HBV) DNA may persist in the liver in the absence of serum HBV–DNA after a self‐limited acute hepatitis B. This may also occur in patients with chronic hepatitis C virus (HCV) infection but its prevalence and its impact on liver histology is unknown. HBV–DNA was tested by polymerase chain reaction (PCR) and by in situ hybridisation in liver biopsies from 98 patients with chronic hepatitis C who were hepatitis B surface antigen negative and serum HBV–DNA negative by PCR. HBV–DNA resulted positive in the liver of 37/98 (37.7%) patients without serum HBV–DNA. To test whether these patients had serum HBV–DNA levels under the detection limit of the PCR assay used in this study (50 copies/ml), PCR products in which HBV–DNA was undetectable after visualization of agarose gels were analysed by dot‐blot hybridisation. With this method, HBV–DNA was positive in serum of 12/37 patients with liver HBV–DNA. Thus, 25/98 (25.5%) patients have HBV–DNA detectable only in liver. This was confirmed by in situ hybridisation, the percentage of infected hepatocytes ranging from 0.1% to 12%. In patients in whom the HCV infection was shorter than 20 years, HBV infected patients had higher (P = 0.01) fibrosis score (1.64 ± 1.21) than HBV negative cases (0.53 ± 0.66). In conclusion, a significant proportion of patients with chronic HCV infection have HBV–DNA in the liver in the absence of viral DNA in serum. The impact of this finding on liver histology deserves further research. J. Med. Virol. 73:177–186, 2004. © 2004 Wiley‐Liss, Inc.
Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan
Authors: Toyoda Hidenori , Hayashi Kazuhiko , Murakami Yoshiki , Honda Takashi , Katano Yoshiaki , Nakano Isao , Goto Hidemi , Kumada Takashi , Takamatsu Junki
Published: April 2004

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion‐transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti‐HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)–region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population. J. Med. Virol. 73:195–199, 2004. © 2004 Wiley‐Liss, Inc.
Molecular and serological evaluation of surface antigen negative hepatitis B virus infection in blood donors from Venezuela
Authors: Gutiérrez Cristina , Devesa Marisol , Loureiro Carmen Luisa , León Graciela , Liprandi Ferdinando , Pujol Flor Helene
Published: April 2004

Surface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti‐HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti‐HBc antibodies (>25 UI/ml, P < 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti‐HBs. Synonymous and non‐synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33–45 bp deletions near the N‐terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia. J. Med. Virol. 73:200–207, 2004. © 2004 Wiley‐Liss, Inc.
IL‐10 levels in Dengue patients: Some findings from the exceptional epidemiological conditions in Cuba
Authors: Pérez Ana B. , García Gissel , Sierra Beatriz , Alvarez Mayling , Vázquez Susana , Cabrera María V. , Rodríguez Rosmary , Rosario Delfina , Martínez Eric , Denny Thomas , Guzmán María G.
Published: April 2004

The pathogenesis associated with Dengue haemorrhagic fever, has yet to be fully elucidated, with no definitive in vivo evidence. The exceptional epidemiological circumstances in Cuba allow the evaluation of different mediators in a well‐defined situation. In the present study, we describe the determination of levels of IL‐12, IL‐10 and RANTES in the sera of Cuban patients hospitalised with Dengue fever or Dengue haemorrhagic fever. The results showed that levels of serum IL‐10 were higher in patients than controls, and those patients with secondary infections had consistently higher levels. All the Dengue haemorrhagic fever patients had increased levels of IL‐10. In contrast, levels of IL‐12 did not differ between patients and controls. Finally, RANTES serum levels detected in patients were lower than those observed in the controls. The association of increased levels of IL‐10 in Dengue patients with a sequential infection suggests a possible role of this cytokine in the pathogenesis of Dengue disease. J. Med. Virol. 73:230–234, 2004. © 2004 Wiley‐Liss, Inc.