bluuebunny/crossref_metadata_2025 huggingface dataset:
The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients
Authors: Rodo M. , Czonkowska A. , Pulawska M. , Swiderska M. , Tarnacka B. , Wehr H.
Published: November 2003

The aim of this study was to estimate the level of lipids and of the main serum antioxidant, α‐tocopherol (vitamin E), and to evaluate the susceptibility of low density lipoprotein (LDL) to oxidation in Wilson's disease patients. It was assumed that enhanced LDL peroxidation caused by high copper levels could contribute to the injury of liver and other tissues. The group investigated comprised 45 individuals with Wilson's disease treated with penicillamine or zinc salts and a control group of 36 healthy individuals. Lipids were determined by enzymatic methods, α‐tocopherol by high performance liquid chromatography, the susceptibility of LDL to oxidation in vitro by absorption changes at 234 nm during 5 h and end‐products of LDL lipid oxidation as thiobarbituric acid reacting substances. In Wilson's disease patients total cholesterol, LDL cholesterol and α‐tocopherol levels were significantly lower compared with the control group. No difference in LDL oxidation in vitro between the patients and the controls was stated. Conclusion: enhanced susceptibility of isolated LDL for lipid peroxidation in vitro was not observed in Wilson's disease patients. One cannot exclude, however, that because of low α‐tocopherol level lipid peroxidation in the tissues can play a role in the pathogenesis of tissue injury in this disease.
Hemidystonia secondary to cervical demyelinating lesions
Authors: Yücesan C. , Tuncel D. , Akbostanci M. C. , Yücemen N. , Mutluer N.
Published: November 2003

Hemidystonia is usually associated with a structural lesion in the contralateral basal ganglia. We report a patient with definite multiple sclerosis, according to Poser's criteria, presenting with an acute‐onset sustained left hemidystonia. Cranial T2‐weighted magentic resonance imaging (MRI) showed several hyperintense lesions in the centri semiovali and in the periventricular area without basal ganglia involvement. Moreover cervical spinal cord T2‐weighted MRI showed two hyperintense lesions in the left posterolateral spine at C2 and C3, and one lesion in the right posterolateral spine at C4 levels. The hemidystonia improved completely after daily treatment with 1000 mg of methylprednisolone, and cervical MRI was performed after the improvement which showed that the lesions had become smaller and less intense. Finally we consider that the hemidystonia may be caused by the cervical spinal cord lesions of multiple sclerosis.
Lesion of the anterior branch of axillary nerve in a patient with hereditary neuropathy with liability to pressure palsies
Authors: Simonetti S.
Published: November 2003

We report the case of a 30‐year‐old woman affected by hereditary neuropathy with liability to pressure palsies (HNPP), who developed a painless left axillary neuropathy after sleeping on her left side, on a firm orthopaedic mattress, in her eighth month of pregnancy. Electromyography (EMG) showing neurogenic signs in the left anterior and middle deltoid, and normal findings in the left teres minor, posterior deltoid and other proximal upper limb muscles, demonstrated that the lesion was at the level of the axillary anterior branch. A direct compression of this branch against the surgical neck of the humerus seems the most likely pathogenic mechanism. This is the first documented description of an axillary neuropathy in HNPP. Knowledge of its possible occurrence may be important for prevention purposes.
Identification of Native American Founder mtDNAs Through the Analysis of Complete mtDNA Sequences: Some Caveats
Authors: Bandelt H.‐J. , Herrnstadt C. , Yao Y.‐G. , Kong Q.‐P. , Kivisild T. , Rengo C. , Scozzari R. , Richards M. , Villems R. , Macaulay V. , Howell N. , Torroni A. , Zhang Y.‐P.
Published: November 2003

In this study, a detailed analysis of both previously published and new data was performed to determine whether complete, or almost complete, mtDNA sequences can resolve the long‐debated issue of which Asian mtDNAs were founder sequences for the Native American mtDNA pool. Unfortunately, we now know that coding region data and their analysis are not without problems. To obtain and report reasonably correct sequences does not seem to be a trivial task, and to discriminate between Asian and Native American mtDNA ancestries may be more complex than previously believed. It is essential to take into account the effects of mutational hot spots in both the control and coding regions, so that the number of apparent Native American mtDNA founder sequences is not erroneously inflated. As we report here, a careful analysis of all available data indicates that there is very little evidence that more than five founder mtDNA sequences entered Beringia before the Last Glacial Maximum and left their traces in the current Native American mtDNA pool.
A Metric Linkage Disequilibrium Map of a Human Chromosome
Authors: Tapper W. J. , Maniatis N. , Morton N. E. , Collins A.
Published: November 2003

We used LDMAP (Maniatis et al. 2002) to analyse SNP data spanning chromosome 22 (Dawson et al. 2002), to obtain a whole‐chromosome metric LD map. The LD map, with map distances analogous to the centiMorgan scale of linkage maps, identifies regions of high LD as plateaus (‘blocks’) and characterises steps which define the relationship between these regions. From this map we estimate that block regions comprise between 32% and 55% of the euchromatic portion of chromosome 22 and that increasing marker density within steps may increase block coverage. Steps are regions of low LD which correspond to areas of variable recombination intensity. The intensity of recombination is related to the height of the step and thus intense recombination hot‐spots can be distinguished from more randomly distributed historical events. The LD maps are more closely related to the high‐resolution linkage map (Kong et al. 2002) than average measures of ρ with recombination accounting for between 34% and 52% of the variance in patterns of LD (r = 0.58 – 0.71, p = 0.0001). Step regions are closely correlated with a range of sequence motifs including GT/CA repeats. The LD map identifies holes in which greater marker density is required and defines the optimal SNP spacing for positional cloning, which suggests that some multiple of around 50,000 SNPs will be required to efficiently screen Caucasian genomes. Further analyses which investigate selection of informative SNPs and the effect of SNP allele frequency and marker density will refine this estimate.
Plasma Exchange Treatment Improves Prognosis of Antineutrophil Cytoplasmic Antibody‐associated Crescentic Glomerulonephritis: A Case‐Control Study in 26 Patients from a Single Center
Authors: Frascà Giovanni M , Soverini Maria Letizia , Falaschini Alessandra , Tampieri Elena , Vangelista Alba , Stefoni Sergio
Published: November 2003

Abstract:  Twenty‐six patients with Antineutrophil cytoplasmic antibody (ANCA)‐associated crescentic glomerulonephritis (GN) were divided into two groups according to the acute phase treatment: drug therapy consisting of steroids and oral cyclophosphamide plus a plasma exchange (PE) course (group A, 13 patients) or drug therapy alone (group B, 13 patients). Group A patients had a more severe clinical picture and higher serum creatinine than group B (12.7 ± 6.9 vs. 8.5 ± 5.3 mg%); nine patients from group A (69%) and five from group B (38%) required dialysis. At follow up (mean 35 months) all patients treated with PE were alive; four of them were in end‐stage renal disease. Among group B patients, three (23%) died in the acute phase; 6 (46%) needed renal replacement therapy at follow up. Of the dialysis‐dependent patients, five out of nine from group A were free of dialysis, while in group B two out of five patients had died, two had entered a regular dialysis treatment and one had received a cadaver graft. These data suggest  that  PE  may  significantly  improve  the  prognosis of patients with ANCA‐associated crescentic GN even if they are  not  dialysis‐dependent  at  the  time  of diagnosis.
Successful Treatment of Ulcerative Colitis with Leukocytapheresis Using Non‐woven Polyester Filter
Authors: Sakata Hiromi , Kawamura Naoyuki , Horie Takashi , Ohizumi Hiroko , Tamaki Tohru , Kukita Kazutaka , Meguro Jun‐ichi , Yonekawa Motoki , Saitoh Masao , Kawamura Akio
Published: November 2003

Abstract:  Ulcerative colitis is a chronic inflammatory disease of the rectum and colon. Although the pathogenesis of ulcerative colitis is not fully elucidated, cell‐mediated immunity plays an important role in disease pathogenesis. Leukocytapheresis is a newly emerging therapy to eliminate activated leukocyte from systemic circulation. We have studied the effects of leukocytapheresis on patients with ulcerative colitis who had failed to respond to conventional therapy. A total of 51 patients with ulcerative colitis were treated with apheresis using a non‐woven polyester fiber filter (Finecell, Asahi Medical Co., Tokyo, Japan) originally developed as a microcoagulation elimination filter for massive transfusion. Of the 51 patients, 33 (64.7%) achieved clinical remission manifested by clinical activity and colonoscopic findings without any adverse effects. This result suggested that leukocytapheresis using Finecell might serve as an alternative therapy for ulcerative colitis as other leukocytapheresis using centrifugation or column.
Therapeutic Apheresis Therapy for ABO‐incompatible Renal Transplantations
Authors: Ishida Hideki , Tanabe Kazunari , Toma Hiroshi , Akiba Takashi
Published: November 2003

Abstract:  The most important transplantation antigen system for organ transplantation is the ABO blood group system. Crossing the blood barrier is usually not done except in emergency cases such as liver transplantations for fulminant hepatitis. Early experiences of allograft transplantations across the blood barriers were discouraging. In the 1970s, clinical trials were started transplanting kidneys of subgroup A2 into blood group O recipients because the tissues of the A2 subgroup express a lower amount of A antigens compared with subgroup A1. The recipients required no special treatment and received the standard immunosuppressive regimen as used in blood group identical cases. Many early graft loses immediately after transplantations were experienced, but these trials resulted in an excellent graft survival rate. A few centers have adapted the concept of A2 kidneys to non‐A recipient transplantations with successful results by reducing anti‐A blood type titers prior to transplantations. In the early 1980s, the possibility of bridging the ABO barrier was tested by several groups. A1 and B kidneys from living donors were also successfully transplanted across the blood barrier using quadruple immunosuppressive drugs and splenectomy. Since 1989, the largest number of ABO‐incompatible renal transplantations have been performed in Japan because of the limited numbers of cadaveric donors. Approximately 400 cases have been successfully transplanted across the blood barrier at many centers in Japan. Owing to novel immunosuppressive drugs, the ABO‐incompatible allografts exhibited a level of function comparable with that of ABO‐matched allografts even though anti‐A or anti‐B antibodies had returned to the circulation of the recipients. In this article, we describe the historical background, the current therapeutic strategies including apheresis therapy for the ABO‐incompatible transplantations, and the experiences at our institution.
Immunomodulation Effects and Clinical Evidence of Apheresis in Renal Diseases
Authors: Yokoyama Hitoshi , Wada Takashi , Furuichi Kengo
Published: November 2003

Abstract:  This article overviews the immunomodulation effects and clinical evidence of apheresis in renal diseases, in particular primary and secondary glomerulonephritis. A considerable permeability factor(s) derived from circulating T cells is speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE), immunoadsorption using Protein A sepharose cartridges, low‐density lipoprotein apheresis and lymphocyte apheresis (LCAP) were tried to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as antiglomerular basement membrane antibodies, antineutrophil cytoplasmic antibodies and immune‐complexes such as lupus nephritis were also treated with PE, double filtration plasma apheresis, IAPP and LCAP. Many reports suggested that apheresis might have beneficial immunomodulation effects for the treatment of glomerular diseases; however, the recommendations  based  on  evidence  from  small  cohorts  remain  at low‐level in most.
Logistic Regression Models for Polymorphic and Antagonistic Pleiotropic Gene Action on Human Aging and Longevity
Authors: Tan Qihua , Bathum L. , Christiansen L. , Benedictis G. De , Dahlgaard J. , Frizner N. , Vach W. , Vaupel J. W. , Yashin A. I. , Christensen K. , Kruse T. A.
Published: November 2003

In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic situation. Genotype and allele‐based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture the age‐dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age‐dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important gene variations that contribute to human aging and longevity.
SNP Subset Selection for Genetic Association Studies
Authors: Byng M. C. , Whittaker J. C. , Cuthbert A. P. , Mathew C. G. , Lewis C. M.
Published: November 2003

Association studies for disease susceptibility genes rely on the high density of SNPs within candidate genes. However, the linkage disequilibrium between SNPs imply that not all SNPs identified in the candidate region need be genotyped. Here we develop several approaches to SNP subset selection, which can substantially reduce the number of SNPs to be genotyped in an association study. We apply clustering algorithms to pairwise linkage disequilibrium measures, with SNP subsets determined for different cut‐off values of Δ using nearest and furthest neighbour clusters. Alternatively, SNP subsets may be determined by the proportion of haplotypes they identify. We also show how power calculations, based on the average power to identify a SNP as the disease susceptibility mutation using haplotype‐based or logistic regression based statistical analyses, can be used to choose SNP subsets. All these methods provide a ranking method for subsets of a specific size, but do not provide criteria for overall choice of SNP subset size. We develop such criteria by incorporating power calculations into a decision analysis, where the choice of SNP subset size depends on the genotyping costs and the perceived benefits of identifying association. These methods are illustrated using eleven SNPs in the MMP2 gene.
Power of Linkage Disequilibrium Mapping to Detect a Quantitative Trait Locus (QTL) in Selected Samples of Unrelated Individuals
Authors: Tenesa A. , Knott S. A. , Carothers A. D. , Visscher P. M.
Published: November 2003

We considered a strategy to map quantitative trait loci (QTLs) using linkage disequilibrium (LD) when the QTL and marker locus were multiallelic. The strategy involved phenotyping a large number of unrelated individuals and genotyping only selected individuals from the two tails of the trait distribution. Power to detect trait‐marker association was assessed as a function of the number of QTL and marker alleles. Two patterns of LD were used to study their influence on power. When the frequency of the QTL allele with the largest effect and that of the marker allele linked in coupling were equal, power was maximum. In this case, increasing the number of QTL alleles reduced the power. The maximum difference in power between the two LD patterns studied was ∼30%. For low QTL heritabilities (h2QTL < 0.1) and single trait studies we recommend selecting around 5% of the upper and lower tails of the trait distribution.
A 34 bp Deletion WithinTSC2is a Rare Polymorphism, not a Pathogenic Mutation
Authors: Roberts Penelope S. , Ramesh Vijaya , Dabora Sandra , Kwiatkowski David J.
Published: November 2003

Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome due to mutations in eitherTSC1orTSC2. Previous reports have identified a mutation consisting of a 34 bp deletion affecting portions of exon 38 and the adjacent intron 38 ofTSC2. We found this genetic variation in 4 of 800 TSC patients screened for mutations inTSC1andTSC2. In every case, the variant was present in one unaffected parent of the sporadically affected TSC child. By RT‐PCR analysis of RNA samples from two additional families with this genetic variant, we demonstrate that the allele with the deletion generates about 50% normal RNA transcript, and 50% RNA transcript including intron 38. In addition, there is no correlation between the extent of splicing and clinical status of family members. We also excluded the possibility of mosaicism in the parents with this variant. We conclude that this deletion is a rare polymorphism that does not cause TSC, but may be a modifier of the TSC phenotype.
An Analysis of Consanguinity and Social Structure Within the UK Asian Population Using Microsatellite Data
Authors: Overall A. D. J. , Ahmad M. , Thomas M. G. , Nichols R. A.
Published: November 2003

We analysed microsatellite genotypes sampled from the Pakistani and Indian communities in Nottingham, UK, to investigate the genetic consequences of substructuring mediated by traditional marriage customs. The application of a recently developed likelihood approach identified significant levels of population substructure within the Pakistani community as a whole, as well as within the finer divisions of castes and biradheri. In addition, high levels of cryptic or unacknowledged consanguinity were detected within subgroups of this community, including biradheri. The Indian sample showed no significant evidence of either substructure or consanguinity. We demonstrate that estimates of disease gene frequencies can be inaccurate unless they are made jointly with estimates of population substructure and consanguinity ((θ≡FST) and C). The magnitude of these estimates also highlights the importance of accounting for the finer scale of social structuring when making decisions regarding the risk of recessive disorders in offspring.
Testing the Genetic Relation Between Two Individuals Using a Panel of Frequency‐unknown Single Nucleotide Polymorphisms
Authors: Lee W.‐C.
Published: November 2003

The author proposes a method to test the genetic relation between two individuals using a panel of SNPs. The method does not require information about the allele frequencies, and as such it can be used to test any pair of individuals from any population(s).
Tests for Candidate‐Gene Association Using Case‐Parents Design
Authors: Zheng G. , Chen Z. , LI Z.
Published: November 2003

In the case‐parents design for testing candidate‐gene association, the conditional likelihood method based on genotype relative risks has been developed recently. A specific relation of the genotype relative risks is referred to as a genetic model. The efficient score tests have been used when the genetic model is correctly specified under the alternative hypothesis. In practice, however, it is usually not able to specify the genetic model correctly. In the latter situation, tests such as the likelihood ratio test (LRT) and the MAX3 (the maximum of the three score statistics for dominant, additive, and recessive models) have been used. In this paper, we consider the restricted likelihood ratio test (RLRT). For a specific genetic model, simulation results demonstrate that RLRT is asymptotically equivalent to the score test, and both are more powerful than the LRT. When the genetic model cannot be correctly specified, the simulation results show that RLRT is most robust and powerful in the situations we studied. MAX3 is the next most robust and powerful test. The TDT is the easiest statistic to compute, compared to MAX3 and RLRT. When the recessive model can be eliminated, it is also as robust and powerful as RLRT for other genetic models.
A Note on Including Phenotypic Information from Monozygotic Twins in Variance Components Qtl Linkage Analysis
Authors: Evans D. M. , Medland S. E.
Published: November 2003

Williams & Blangero (1999) derived closed form expressions for the power of a univariate variance components test of linkage for a variety of pedigree structures. We have extended their results by investigating the effect of including monozygotic twins in the design on the power to detect linkage. Specifically, we determined the power associated with a pedigree of size three, where individuals one and two were monozygotic twins and individual three was a full sibling to the twins. The power of this sampling unit was uniformly greater than the power obtained from a sib‐pair under the same genetic model. The reason for this was that addition of a second monozygotic twin provided another estimate of the sibling correlation for the particular IBD class. In addition, when the total heritability of the trait was <50%, the number of individuals that needed to be phenotyped was less than that with sib‐pairs alone. However, a pedigree consisting of a monozygotic pair and sibling was never as informative as a sib‐trio, presumably because the sib‐trio provided information about allele sharing between three individuals, whereas the monozygotic twins and sibling unit only provided one such relationship. We conclude that including a monozygotic twin in the analysis is an economical strategy, since only one twin needs to be genotyped.
Ray chaos and ray clustering in an ocean waveguide
Authors: Makarov D. V. , Uleysky M. Yu. , Prants S. V.
Published: November 2003

We consider ray propagation in a waveguide with a designed sound-speed profile perturbed by a range-dependent perturbation caused by internal waves in deep ocean environments. The Hamiltonian formalism in terms of the action and angle variables is applied to study nonlinear ray dynamics with two sound-channel models and three perturbation models: a single-mode perturbation, a randomlike sound-speed fluctuations, and a mixed perturbation. In the integrable limit without any perturbation, we derive analytical expressions for ray arrival times and timefronts at a given range, the main measurable characteristics in field experiments in the ocean. In the presence of a single-mode perturbation, ray chaos is shown to arise as a result of overlapping nonlinear ray-medium resonances. Poincaré maps, plots of variations of the action per ray cycle length, and plots with rays escaping the channel reveal inhomogeneous structure of the underlying phase space with remarkable zones of stability where stable coherent ray clusters may be formed. We demonstrate the possibility of determining the wavelength of the perturbation mode from the arrival time distribution under conditions of ray chaos. It is surprising that coherent ray clusters, consisting of fans of rays which propagate over long ranges with close dynamical characteristics, can survive under a randomlike multiplicative perturbation modelling sound-speed fluctuations caused by a wide spectrum of internal waves.
Size segregation in rapid, granular flows with continuous size distributions
Authors: Dahl S. R. , Hrenya C. M.
Published: November 2003

Two-dimensional (dissipative) molecular-dynamics simulations of particulate mixtures with Gaussian and lognormal particle size distributions are employed to gain insight on the segregation behavior of these mixtures when exposed to a granular temperature gradient. Simulations are performed for a collection of smooth, inelastic, hard disks (with constant material density and a constant coefficient of restitution) confined between two walls set to constant, though unequal, granular temperatures. As a result, a gradient in granular temperature develops across the domain. In general, particles of all sizes are found to move toward regions of low granular temperature (overall segregation). Species segregation is also observed. Specifically, large particles demonstrate a higher affinity for the low-temperature regions, and thus accumulate in these cool regions to a greater extent than their smaller counterparts. Furthermore, the local particle size distribution remains of the same form (Gaussian or lognormal) as the overall (including all particles) size distribution. In addition, the behaviors of Gaussian size distributions and narrow lognormal distributions are found to be quite similar.
Fluid–body interaction in the presence of uniform vorticity and density gradient
Authors: Miloh T.
Published: November 2003

We consider the case of a rigid or deformable body moving in a linear shear flow of an inviscid, incompressible and inhomogeneous fluid with a uniform density gradient. The body is impulsively introduced into the nonuniform ambient flow field possessing time-dependent vorticity. In order to make the analysis amenable, it is further assumed that the size of the body is small with respect to the inhomogeneity of the ambient flow. By integrating the Euler equation it is shown that analytic expressions can be obtained for the hydrodynamical reactions (forces and moments) acting on the body which determine its trajectories. In addition to the traditional purely inertial quadratic terms, three new types of interaction modes are thus revealed: Vorticity-inertia, density gradient-inertia, and vorticity-density gradient. The first two modes have been considered separately just recently but the third one is presented here for the first time. It is finally demonstrated that all three modes of interaction can be obtained from a relatively straightforward unified approach.
The effect of insoluble surfactant at dilute concentration on drop breakup under shear with inertia
Authors: Drumright-Clarke M. A. , Renardy Y.
Published: November 2003

Direct numerical simulations are conducted with a volume-of-fluid continuous surface stress algorithm. The linear equation of state is used to characterize the effects of an insoluble surfactant at low concentration on a drop in strong shear. The drop and the surrounding liquid have the same viscosity and density. Surfactant migration induces a Marangoni force that acts toward the drop center. For low inertia, viscous force opposes the Marangoni force, so that a stationary drop with surfactant is more elongated and less tilted than without. The addition of surfactant promotes breakup, lowering the critical capillary number. The first daughter drops are smaller than for the case of clean drops. For high inertia, the Marangoni force retracts the drop and retards breakup. The local values of surface tension are computed during drop evolution.
Instability of a rotating thread in a second immiscible liquid
Authors: Ashmore J. , Stone H. A.
Published: November 2003

We consider the surface-tension-driven instability of a cylindrical liquid column surrounded by a second liquid when the entire system is rotating. Our calculations are in the limit that the flows in both the liquid thread and the outer fluid are viscously dominated, and include the centripetal and Coriolis forces; the effect of the Coriolis force has not previously been studied in the case that the flows in both liquids are viscous. We present numerical results of a linear temporal stability analysis, and an analytical result valid in the large-Taylor-number limit. We also use the boundary-integral method to consider the evolution and instability of a finite cylindrical thread, which then relaxes when the rotation rate is reduced. These results are discussed in connection with recent experimental observations.
On the Faraday instability in a surfactant-covered liquid
Authors: Kumar Satish , Matar Omar K.
Published: November 2003

The formation of standing waves at the surfactant-covered free surface of a vertically-vibrated liquid is analyzed in this work. Assuming that the surfactants are insoluble and the effects of lateral boundaries are negligible, linear stability analysis and Floquet theory are applied to the governing equations. A recursion relation involving the temporal modes of the free-surface deflection and surfactant concentration variation results, and is solved to determine the critical vibration amplitude needed to excite the standing waves and the corresponding critical wave number. It is found that the critical vibration amplitude shows a minimum with respect to the Marangoni number, meaning that surfactants can potentially lower the value of the critical amplitude relative to its value for an uncontaminated free surface. The critical wave number, however, is found to be an increasing function of the Marangoni number. Analysis of the phase-angle difference between the free-surface deflection and the surfactant concentration variation suggests that the minimum in the critical amplitude arises because the Marangoni flows help produce a velocity field near the free surface similar to that which would be present if the liquid were inviscid.
Magneto-Structural Correlation in Di-μ-oxo Bridged Dicopper Complexes—Predictability of Isotropic Exchange-Coupling Constant from Structure
Authors: Chandramouli G. V. R. , Kundu T. K. , Manoharan P. T.
Published: November 2003

The relation between isotropic exchange-coupling constant and their structural parameters was examined using 117 compounds containing di-μ-oxo dicopper (CuO2Cu) moiety. The Cu–O bond distances should be in the range of covalent bonding region, preferably 1.93 Å and should be less than 2.25 Å for the superexchange path. The scatter plot between the Cu–O–Cu angle (φ) versus Cu ... Cu distance (r) suggests that large number of molecules have a Cu–O bond length of 1.93 Å, and their Cu ... Cu distances are determined by φ. The atoms attached to bridging oxygen and ligands of copper can influence the exchange-coupling constant to a larger extent when compared to other distortions like deviation from planarity and ideal bond lengths and angles. It is suggested that the superexchange pathway is ineffective at Cu–O distances greater than 2.25 Å resulting into |2J| < 50 cm–1 and no magneto-structural correlation for these systems could be given. The magneto-structural correlations are given by 2J [cm–1] = –99.1 φ [°] + 9587 = –4600 r [Å] + 13 226. A study including only four-coordinate copper atoms indicate that 2J = (2/rCu-O)(–74.8 φ + 7126 + B) where rCu-O is the Cu–O bond length and B is a correction term applied based on distortions and atoms attached to bridging oxygen and copper atoms. The above least-squares fit lines indicate continuity between antiferromagnetic and ferromagnetic regions crossing the 2J = 0 value at around 97°.
Substituent Effects in the Reduction Behaviour of Thio- and Oxopyrimidines in Non-Aqueous Solvents
Authors: Borsari Marco , Cannio Maria , Dallari Daniela , Fontanesi Claudio , Gavioli Giovanna , Peressini Silvia , Tavagnacco Claudio
Published: November 2003

The electrochemical reduction of a series of thio- and oxopyrimidine derivatives has been investigated in organic solvents on mercury electrodes. In all cases the electrochemical process gave a dimeric species as the major product. The overall reduction mechanism is the same for oxo and thio derivatives, and is found to be dependent only on the nature of the ring nitrogen substituent. A ‘father–son reaction’ is observed when hydrogen is bound to the ring nitrogen atom: the radical anion obtained from the first electron transfer draws out the nitrogen proton of a non-reduced molecule and this then dimerizes. In the presence of a protonating agent as well as for the N-substituted derivatives, the ‘father–son reaction’ is not observed. Theoretical calculations have been performed to gain insight into the proposed mechanisms: the LUMO energy and the vertical electron affinity show a linear correlation with the reduction potentials. Analysis of the theoretical parameters has allowed step-by-step determination of the electrochemical reduction process. The manner in which solvent properties influence electrochemical behaviour has been examined, and the role of the acceptor number (AN) has been discussed.
HPLC Separation of Diastereomeric Metal Complexes of the Form Δ,Λ-[Ru(diimine)2(S)-aminoacidate]
Authors: Aldrich-Wright Janice R. , Vagg Robert S. , Williams Peter A.
Published: November 2003

Complete separation of the photosensitive diastereomeric complexes of the general form [Ru(diimine)2(S)-aminoacidate], in which the diimine is 1,10-phenanthroline (phen) or 2,2′-bipyridine (bpy) and S-amino or N-methyl-S-aminoacidate are S-aspartate, S-tryptophanate or N-methyl-S-tryptophanate, has been achieved by reversed-phase ion-interaction chromatography. This has allowed the photo-equilibrated isomeric ratios for each complex to be estimated.
Evaluating the potential health gain of the World Health Organization's recommendation concerning vegetable and fruit consumption
Authors: Hoffmann Kurt , Boeing Heiner , Volatier Jean-Luc , Becker Wulf
Published: November 2003

Objective:

The World Health Organization (WHO) recommends a daily intake of at least 400?g of vegetables and fruit. The aim of this paper was to evaluate the public health benefit of meeting this WHO recommendation by applying a statistical method that combines estimated intake distributions and simulated intake changes.

Design and setting:

The benefit of an increased consumption of vegetables and fruit was quantified by the preventable proportion of diseases. This proportion was estimated by a general formula derived in the paper that incorporates individual relative risks. Three different strategies of increasing usual intake were simulated and compared. The first strategy assumes that all individuals increase their intake by the same amount, the second assumes a constant increase among low consumers, and the third simulates individual increments necessary to meet the WHO recommendation. Calculations were made for three different scenarios with varying relative risks.

Results:

The third simulation strategy turned out to be the most appropriate one to quantify the potential health gain of the current dietary recommendation. Applying this strategy to prevent cancer, the proportion of preventable cases was country-specific. Estimates for France and Sweden were 21.9% and 19.3%, respectively, which are somewhat lower than the non-specific figure published by the World Cancer Research Fund.

Conclusions:

To improve estimates of the preventable proportion of diseases, the estimation formula presented here can be applied. Its application requires intake data to estimate the initial intake distribution in the population and to simulate adequate dietary changes.
Transfection of prion protein gene suppresses coxsackievirus B3 replication in prion protein gene-deficient cells
Authors: Nakamura Yuko , Sakudo Akikazu , Saeki Keiichi , Kaneko Tomomi , Matsumoto Yoshitsugu , Toniolo Antonio , Itohara Shigeyoshi , Onodera Takashi
Published: November 2003

The susceptibility of prion protein gene (Prnp)-null cells to coxsackievirus B3 (CVB3) was investigated. Primary cultures of murinePrnp−/−brain cells were more sensitive to CVBs than corresponding cells from wild-type mice. The viral susceptibility of aPrnp-null cell line (HpL3-4) derived from the murine hippocampus was compared with that of two established cell lines (HeLa and HEp-2) that are widely employed for CVB3 studies. After infection with CVB3, HpL3-4 cells showed a very rapid and complete cytopathic effect (CPE). CPE developed earlier and viruses replicated at higher titres in HpL3-4 cells compared with HeLa and HEp-2 cells. Under a semi-solid medium, plaques developed rapidly in CVB3-infected HpL3-4 cells. To confirm the effect ofPrnpon virus infection, aPrnp−/−cell line and aPrnp-transfected neuronal cell line were analysed. The replication and release of infectious particles of CVB3 inPrnp−/−cells were significantly more effective than those of thePrnp-transfected cell line. Levels of type I interferon (IFN) after CVB3 infection were higher in thePrnp-transfected cell line than inPrnp−/−cells, whereas apoptotic cells were more obvious in thePrnp−/−cells than in those of thePrnp-transfected cell line. These findings suggest that the absence ofPrnpretards the induction of CVB3-induced IFNs, resulting in an enhanced CVB3 production and apoptotic cell death. Furthermore, our data indicate that the HpL3-4 cell line may provide a novel and sensitive system for isolation of CVB3 from clinical specimens.
A promoter within the E6 ORF of human papillomavirus type 16 contributes to the expression of the E7 oncoprotein from a monocistronic mRNA
Authors: Glahder Jacob A. , Hansen Christina N. , Vinther Jeppe , Madsen Birger S. , Norrild Bodil
Published: November 2003

Human papillomavirus type 16 (HPV-16) has the capacity to transform human primary keratinocytes. Maintenance of the transformed phenotype requires constitutive expression of the oncoproteins E6 and E7. The low-risk HPV types express E7 from monocistronic mRNA, but for the high-risk types, no mRNA that encodes E7 as the first open reading frame (ORF) has been identified. We recently identified a transcription initiation site within the E6 ORF of HPV-16 at nt 542. In the present study we have characterized the P542 promoter, which putatively controls monocistronic expression of E7. The monocistronic mRNA is not very abundant, but we have shown that an E7–luciferase fusion protein can be expressed in SiHa cells from a monocistronic HPV-16 transcript initiated at nt 542. The monocistronic mRNA expresses E7–luciferase more efficiently than the most abundant in vivo-like mRNA E6*IE7, initiated by P97 and spliced from nt 226 to 409. Furthermore, the translation initiation of E7 is most abundant from the monocistronic mRNA. We have also shown that the P542 promoter is downregulated by the transcription factor activator protein 4 (AP-4) and the differentiation-dependent factor hSkn-1a, both binding downstream of the transcription initiation site. In conclusion, we have found that P542 is a relatively weak promoter compared with P97 and may be downregulated in differentiated epithelial cells.
Transcriptional activation of immediate–early gene ETR101 by human T-cell leukaemia virus type I Tax
Authors: Chen Li , Ma Shiliang , Li Bo , Fink Trine , Zachar Vladimir , Takahashi Mark , Cuttichia Jamie , Tsui Lap-Chee , Ebbesen Peter , Liu Xiangdong
Published: November 2003

Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate–early geneETR101expression in HTLV-I-infected cells and its regulation by Tax.ETR101was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression ofETR101was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated theETR101gene promoter in a transient transfection assay. A series of deletion and mutation analyses of theETR101gene promoter indicated that a 35 bp region immediately upstream of the TATA-box sequence, which contains a consensus cAMP response element (CRE) and a G+C-rich sequence, is the critical responsive element for Tax activation. Site-directed mutagenesis analysis of the 35 bp region suggested that both the consensus CRE motif and its upstream G+C-rich sequence were critical for Tax transactivation. Electrophoretic mobility shift analysis (EMSA) using the 35 bp sequence as probe showed the formation of a specific protein–DNA complex in HTLV-I-infected cell lines. EMSA with specific antibodies confirmed that the CREB transcription factor was responsible for formation of this specific protein–DNA complex. These results suggested that Tax directly transactivatedETR101gene expression, mainly through a CRE sequence via the CREB transcription pathway.
A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication
Authors: Cocude C. , Truong M.-J. , Billaut-Mulot O. , Delsart V. , Darcissac E. , Capron A. , Mouton Y. , Bahr G. M.
Published: November 2003

In an effort to define novel cellular factors regulating human immunodeficiency virus type 1 (HIV-1) replication, a differential display analysis has been performed on endogenously infected cells stimulated with the HIV-suppressive immunomodulator Murabutide. In this study, the cloning and identification of a Murabutide-downregulated gene, named RH116, bearing classical motifs that are characteristic of the DExH family of RNA helicases, are reported. The 116 kDa encoded protein shares 99·9 % similarity with MDA-5, an inducible RNA helicase described recently. Ectopic expression of RH116 in HeLa-CD4 cells inhibited cell growth and cell proliferation but had no measurable effect on programmed cell death. RH116 presented steady state cytoplasmic localization and could translocate to the nucleus following HIV-1 infection. Moreover, the endogenous expression of RH116, at both the transcript and protein levels, was found to be considerably upregulated after infection. Overexpression of RH116 in HIV-1-infected HeLa-CD4 cells also resulted in a dramatic increase in the level of secreted viral p24 protein. This enhancement in virus replication did not stem from upregulated proviral DNA levels but correlated with increased unspliced and singly spliced viral mRNA transcripts. These findings implicate RH116 in the regulation of HIV-1 replication and point to an apoptosis-independent role for this novel helicase in inducing cell growth arrest.
The immune control and cell-to-cell spread of human T-lymphotropic virus type 1
Authors: Bangham Charles R. M.
Published: November 2003

Human T-lymphotropic virus type 1 (HTLV-1) varies little in sequence compared with human immunodeficiency virus type 1 (HIV) and it is difficult to detect HTLV-1 mRNA, proteins or virions in fresh blood. But the strong and chronically activated T cell response to the virus indicates that HTLV-1 proteins are expressed persistently. It now appears that the efficiency of an individual's cytotoxic T cell (CTL) response to HTLV-1 is the chief single determinant of that person's provirus load, which can differ between HTLV-1-infected people by more than 10 000-fold. Progress is now being made towards defining this CTL ‘efficiency’ in terms of host genetics, T cell function, T cell gene expression and mathematical dynamics. Lymphocytes that are naturally infected with HTLV-1 do not produce enveloped extracellular virions in short-term culture and this has reinforced the erroneous conclusion that the virus is latent. But recent evidence shows that HTLV-1 can spread directly between lymphocytes across a specialized, virus-induced cell–cell contact – a ‘viral synapse’. Instead of making extracellular virions, HTLV-1 uses the mobility of the host cell to spread within and between hosts. In this review the evidence is summarized on the persistent gene expression of HTLV-1in vivo, the role of the immune system in protection and pathogenesis in HTLV-1 infection, and the mechanism of cell-to-cell spread of HTLV-1.
Induction of an antigen-specific immune response and partial protection of cattle against challenge infection with foot-and-mouth disease virus (FMDV) after lipopeptide vaccination with FMDV-specific B-cell epitopes
Authors: Höhlich Bettina-Judith , Wiesmüller Karl-Heinz , Haas Bernd , Gerner Wilhelm , Correa Roberto , Hehnen Hans-Robert , Schlapp Tobias , Pfaff Eberhard , Saalmüller Armin
Published: November 2003

To evaluate the potential of chemically synthesized lipopeptides for vaccination against foot-and-mouth disease (FMD), seven lipopeptides containing the immunostimulating principle of bacterial lipoproteins and linear B-cell epitopes of FMDV strain O1Kaufbeuren (O1K) were used to immunize cattle (n=7). Animals were vaccinated once and 21 days after immunization animals were infected with the homologous virus. Four animals were protected. After vaccination, as well as after challenge infection, B- and T-cell responses were examined. Sera were tested for virus- and peptide-specific antibodies and showed after vaccination only a weak antibody response. After challenge infection, an increase in antibody titre was obvious but there was no correlation between antibody titre and protection. The reactivity of the cellular immune system was detected by analyses of PBMCs for virus- and peptide-specific T-lymphocytes. With regard to the virus-specific T-lymphocytes, a heterogeneous reactivity could be shown. No correlation between virus-specific T-cell proliferation and protection was found. Obvious was the fact that all protected animals showed after vaccination a strong T-cell response against at least one of the peptides used for immunization. These results suggest a correlation between the onset of an antigen-specific T-cell reaction and protection.
Generation and precise modification of a herpesvirus saimiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence
Authors: White Robert E. , Calderwood Michael A. , Whitehouse Adrian
Published: November 2003

Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus, and shares considerable homology with the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and Epstein–Barr virus. The generation of herpesvirus mutants is a key facet in the study of virus biology. The use of F-factor-based bacterial artificial chromosomes (BACs) to clone and modify the genomes of herpesviruses has enhanced the variety, precision and simplicity of mutant production. Here we describe the cloning of the genome of HVS non-transforming strain A11-S4 into a BAC. The cloning of the BAC elements disrupts open reading frame (ORF) 15 but the HVS-BAC can still replicate at levels similar to wild-type virus, and can persistently infect fibroblasts. The HVS-BAC was modified by RecA-mediated recombination initially to substitute reporter genes and also to delete the terminal repeats (TR). After deletion of the TR, the HVS-BAC fails to enter a productive virus lytic cycle, and cannot establish a persistent episomal infection when transfected into fibroblast cell lines. This shows that while ORF 15 is dispensable for virus function in vitro, the TR is required for both virus latency and lytic virus production. In addition, the HVS-BAC promises to be a valuable tool that can be used for the routine and precise production and analysis of viral mutants to further explore gammaherpesvirus biology.