bluuebunny/crossref_metadata_2025 huggingface dataset:
The Heart of Heritage: Sociocultural Dimensions of Heritage Language Learning
Authors: He Agnes Weiyun
Published: July 2010

The very notion of heritage language (HL) is a sociocultural one insofar as it is defined in terms of a group of people who speak it. Heritage languages also have a sociocultural function, both as a means of communication and as a way of identifying and transforming sociocultural groups. This article surveys two broad approaches to research on the sociocultural dimensions of HL learning. While both of these approaches acknowledge the close connection and mutual dependency between HL learning processes and sociocultural processes, they differ in that one of them takes a correlational perspective, and the other a social constructivist perspective. This article reviews a selective body of work conducted from each of the two perspectives and concludes with a discussion of the implications of the sociocultural complexity associated with HL learning for research and practice.
Measuring fear of falling and its effect on quality of life and activity
Authors: Perez-Jara J , Walker D , Heslop P , Robinson S
Published: July 2010

In this review, we analyse original research articles in English and Spanish in which fear of falling (FoF) as a long-term syndrome defines the participants, or is the main outcome, or in cases where FoF is a secondary outcome, falls or activity are the main outcomes.

FoF is difficult to measure. Attempts are made to do so by use of single questions or scales. Restriction in activity due to FoF is a secondary outcome and can be an important influence on a person's quality of life. There are also various methods of measuring it by use of single questions or scales, and general questions in basic or instrumental activities of daily living (ADL) indices are frequently used. Other scales or questionnaires about quality of life (such as the SF-36) or activity (such as the Survey of Activity and Fear of Falling Scales (SAFE), or the Groningen Activity Restriction Scale (GARS)) are also used. The varying objectives of the analysed articles explain some of the variations in measures used. Further work is required to reach a consensus on definition and standardized measurement of FoF and its effect on quality of life and activity.
Production of transgenic rabbit embryos through intracytoplasmic sperm injection
Authors: Li Qiuyan , Hou Jian , Wang Sheng , Chen Yongfu , An Xiao-Rong
Published: July 2010

The objective of this study was to test if intracytoplasmic sperm injection (ICSI)-mediated gene transfer was an effective method in the production of transgenic rabbit embryos. Rabbit sperm diluted in different media with various pH were treated by freezing without cryoprotectant, and their ability for DNA uptake was determined. In these experiments using production of transgenic rabbit embryos by ICSI, exogenous genes at three concentrations and of two conformation types were used. The rate of DNA association to the sperm seen by rhodamine-tagged DNA encoding green fluorescent protein (GFP) was 90.0%, 92.7%, 91.0%, 91.7%, and 92.3%, respectively in TCM199, DM, DPBS, CZB, and HCZB media. The DNA attachment to sperm was not affected by media pH within the range of 5.4–9.4 (p > 0.05). Expression of GFP first occurred at the 2-cell stage and continued to blastocyst formation. DNA concentration (between 5, 10, and 20 ng/μl) or conformation (linear and circular) had no effect on the production rate of transgenic embryos. These results indicated that genetically modified rabbit blastocysts can be efficiently produced by ICSI technique.
Addressing spirituality in CBT
Authors: Waller Rob , Trepka Chris , Collerton Daniel , Hawkins James
Published: July 2010

Mental health policy places a requirement on clinicians to address matters of religion and belief, yet practice falls far behind. This paper summarizes a Panel Discussion at the 2008 BABCP Annual Conference attended by over 50 people. The five speakers each presented their experience of working with particular faith groups (Orthodox Jewish, Christian, Muslim) and from an agnostic viewpoint. Common themes are given, as well as practical advice to therapists who find themselves working with people who hold strong faith beliefs they may not share.
Selectivity in a barren landscape: the P450BioI–ACP complex
Authors: Cryle Max J.
Published: July 2010

The cytochromes P450 (P450s) are a superfamily of oxidative haemoproteins that are capable of catalysing a vast range of oxidative transformations, including the oxidation of unactivated alkanes, often with high stereo- and regio-selectivity. Fatty acid hydroxylation by P450s is widespread across both bacteria and higher organisms, with the sites of oxidation and specificity of oxidation varying from system to system. Several key examples are discussed in the present article, with the focus on P450BioI (CYP107H1), a biosynthetic P450 found in the biotin operon of Bacillus subtilis. The biosynthetic function of P450BioI is the formation of pimelic acid, a biotin precursor, via a multiple-step oxidative cleavage of long-chain fatty acids. P450BioI is a member of an important subgroup of P450s that accept their substrates not free in solution, but rather presented by a separate carrier protein. Structural characterization of the P450BioI–ACP (acyl-carrier protein) complex has recently been performed, which has revealed the basis for the oxidation of the centre of the fatty acid chain. The P450BioI–ACP structure is the first such P450–carrier protein complex to be characterized structurally, with important implications for other biosynthetically intriguing P450–carrier protein complexes.
Two days of tau: a meeting focused on its biology and pathology
Authors: Skoulakis Efthimios M.C. , Mudher Amritpal
Published: July 2010

Tauopathies are a clinically diverse group of neurodegenerative dementias involving perturbations of the level or phosphorylation state of the microtubule-binding axonal protein tau. Despite intense effort in recent years, the precise role of tau in the pathology of the various behaviourally and neuropathologically distinct tauopathies, the mechanisms of tau toxicity and the potential functional interaction of tau and amyloid in Alzheimer's disease remain elusive. Nevertheless, novel observations regarding the various aspects of taumisregulation-dependent pathogenesis are emerging from various cellular, vertebrate and invertebrate animal models and are supported by new clinical data. This Focused Meeting brought together scientists working on tau and tauopathies from different disciplines and various experimental models. The aim was to enhance our understanding of the protein itself and disorders associated with its misregulation through synergy.
The role of MSUT-2 in tau neurotoxicity: a target for neuroprotection in tauopathy?
Authors: Wheeler Jeanna M. , Guthrie Chris R. , Kraemer Brian C.
Published: July 2010

We previously developed a transgenic Caenorhabditis elegans model of human tauopathy disorders by expressing human tau in nematode worm neurons to explore genetic pathways contributing to tau-induced neurodegeneration. This animal model recapitulates several hallmarks of human tauopathies, including altered behaviour, accumulation of detergent-insoluble phosphorylated tau protein and neurodegeneration. To identify genes required for tau neurotoxicity, we carried out a forward genetic screen for mutations that suppress tau neurotoxicity. We ultimately cloned the sut-2 (suppressor of tau pathology-2) gene, mutations in which alleviate tau neurotoxicity in C. elegans. SUT-2 encodes a novel subtype of CCCH zinc-finger protein conserved across animal phyla. SUT-2 shares significant identity with the mammalian SUT-2 (MSUT-2). We identified components of the aggresome as binding partners of MSUT-2. Thus we hypothesize that MSUT-2 plays a role in the formation and/or clearance of protein aggregates. We are currently exploring the role of MSUT-2 in tauopathy using mammalian systems. The identification of sut-2 as a gene required for tau neurotoxicity in C. elegans suggests new neuroprotective strategies targeting MSUT-2 that may be effective in modulating tau neurotoxicity in human tauopathy disorders.
Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model
Authors: Ando Kunie , Leroy Karelle , Heraud Céline , Kabova Anna , Yilmaz Zehra , Authelet Michèle , Suain Valèrie , De Decker Robert , Brion Jean-Pierre
Published: July 2010

We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30×TauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30×TauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.
Brr2p RNA helicase with a split personality: insights into structure and function
Authors: Hahn Daniela , Beggs Jean D.
Published: July 2010

RNA helicases are involved in many cellular processes. Pre-mRNA splicing requires eight different DExD/H-box RNA helicases, which facilitate spliceosome assembly and remodelling of the intricate network of RNA rearrangements that are central to the splicing process. Brr2p, one of the spliceosomal RNA helicases, stands out through its unusual domain architecture. In the present review we highlight the advances made by recent structural and biochemical studies that have important implications for the mechanism and regulation of Brr2p activity. We also discuss the involvement of human Brr2 in retinitis pigmentosa, a degenerative eye disease, and how its functions in splicing might connect to the molecular pathology of the disease.
Regulation of the Phosphoinositide Cascade by Polyamines in Brain
Authors: Periyasamy Sumudra , Kothapalli Madhusudana Rao , Hoss Wayne
Published: July 2010

Abstract: The endogenous polyamines spermidine and spermine enhanced guanosine 5′‐O‐(3‐thiotriphosphate) (GTP‐γ‐S)‐stimulated phosphoinositide turnover with EC50 values of 100 ± 30 and 50 ± 15 µM, respectively, whereas the synthetic polyamines N,N′‐bis(3‐aminopropyl)‐1,3‐propanediamine and ‐ethylenediamine inhibited GTP‐γ‐S‐stimulated phosphoinositide turnover, with maximal inhibition at 1 mM. Kinetic analysis of GTP‐γ‐S‐stimulated phosphoinositide turnover in the absence and presence of spermidine showed that the Km for GTP‐γ‐S was not changed (1,303 ± 270 and 1,069 ± 214 nM, respectively), whereas the Vmax was increased by 206% (1,566 ± 141 and 4,792 ± 84 cpm, respectively), indicating that spermidine and GTP‐γ‐S acted at different sites. Spermidine also enhanced Ca2+‐stimulated phosphoinositide turnover in the absence of GTP‐γ‐S by decreasing the Ca2+ requirement of the phosphoinositide‐specific phospholipase C. Arcaine and agmatine, polyamine antagonists at the NMDA receptor complex, did not block the effects of spermidine on GTP‐γ‐S‐ and Ca2+‐induced phosphoinositide turnover, suggesting that the spermidine effects are not mediated through these specific polyamine sites. Furthermore, spermidine increased the level of [3H]phosphatidylinositol 4‐phosphate (EC50 = 120 ± 10 µM), without affecting significantly the levels of [3H]phosphatidylinositol and [3H]phosphatidylinositol 4,5‐bisphosphate. Collectively these data indicate that the enhanced phosphoinositide turnover induced by spermidine in the presence of GTP‐γ‐S or Ca2+ is mediated through multiple levels of the phosphoinositide turnover cascade.
Optimizing transistor performance of percolating carbon nanotube networks
Authors: Sangwan V. K. , Behnam A. , Ballarotto V. W. , Fuhrer M. S. , Ural Ant , Williams E. D.
Published: July 2010

In percolating networks of mixed metallic and semiconducting carbon nanotubes (CNTs), there is a tradeoff between high on-current (dense networks) and high on/off ratio (sparse networks). Experiments on transistors and Monte Carlo simulations were performed to determine the scaling behavior of device resistivity as a function of channel length (L) for CNT density (p) between 0.04 and 1.29 CNTs/μm2 in the on- and off-states (nanotube root mean square length of 5 μm). Optimized devices with field-effect mobility up to 50 cm2/V s at on/off ratio >103 were obtained at channel width W=50 μm and L>70 μm for p=0.54–0.81 CNTs/μm2.
Phages have adapted the same protein fold to fulfill multiple functions in virion assembly
Authors: Cardarelli Lia , Pell Lisa G. , Neudecker Philipp , Pirani Nawaz , Liu Amanda , Baker Lindsay A. , Rubinstein John L. , Maxwell Karen L. , Davidson Alan R.
Published: July 2010

Evolutionary relationships may exist among very diverse groups of proteins even though they perform different functions and display little sequence similarity. The tailed bacteriophages present a uniquely amenable system for identifying such groups because of their huge diversity yet conserved genome structures. In this work, we used structural, functional, and genomic context comparisons to conclude that the head–tail connector protein and tail tube protein of bacteriophage λ diverged from a common ancestral protein. Further comparisons of tertiary and quaternary structures indicate that the baseplate hub and tail terminator proteins of bacteriophage may also be part of this same family. We propose that all of these proteins evolved from a single ancestral tail tube protein fold, and that gene duplication followed by differentiation led to the specialized roles of these proteins seen in bacteriophages today. Although this type of evolutionary mechanism has been proposed for other systems, our work provides an evolutionary mechanism for a group of proteins with different functions that bear no sequence similarity. Our data also indicate that the addition of a structural element at the N terminus of the λ head–tail connector protein endows it with a distinctive protein interaction capability compared with many of its putative homologues.
Sniffing enables communication and environmental control for the severely disabled
Authors: Plotkin Anton , Sela Lee , Weissbrod Aharon , Kahana Roni , Haviv Lior , Yeshurun Yaara , Soroker Nachum , Sobel Noam
Published: July 2010

Paradoxically, improvements in emergency medicine have increased survival albeit with severe disability ranging from quadriplegia to “locked-in syndrome.” Locked-in syndrome is characterized by intact cognition yet complete paralysis, and hence these individuals are “locked-in” their own body, at best able to communicate using eye blinks alone. Sniffing is a precise sensory-motor acquisition entailing changes in nasal pressure. The fine control of sniffing depends on positioning the soft palate, which is innervated by multiple cranial nerves. This innervation pattern led us to hypothesize that sniffing may remain conserved following severe injury. To test this, we developed a device that measures nasal pressure and converts it into electrical signals. The device enabled sniffs to control an actuator with speed similar to that of a hand using a mouse or joystick. Functional magnetic resonance imaging of device usage revealed a widely distributed neural network, allowing for increased conservation following injury. Also, device usage shared neural substrates with language production, rendering sniffs a promising bypass mode of communication. Indeed, sniffing allowed completely paralyzed locked-in participants to write text and quadriplegic participants to write text and drive an electric wheelchair. We conclude that redirection of sniff motor programs toward alternative functions allows sniffing to provide a control interface that is fast, accurate, robust, and highly conserved following severe injury.
GalR2-positive allosteric modulator exhibits anticonvulsant effects in animal models
Authors: Lu Xiaoying , Roberts Edward , Xia Fengcheng , Sanchez-Alavez Manuel , Liu Tianyu , Baldwin Roger , Wu Stephanie , Chang James , Wasterlain Claude G. , Bartfai Tamas
Published: July 2010

Galanin receptors type 1 (GalR1) and/or type 2 (GalR2) represent unique pharmacological targets for treatment of seizures and epilepsy. Previous studies have shown that the endogenous peptide ligand galanin exerts powerful anticonvulsant effect through activation of these two G protein-coupled receptors, which are highly expressed in the temporal lobe of rodent brain. Here we report the characterization of a putative GalR2-positive allosteric modulator CYM2503. CYM2503 potentiated the galanin-stimulated IP1 accumulation in HEK293 cells stably expressing GalR2 receptor, whereas it exhibited no detectable affinity for the
125
I galanin–binding site of GalR2 receptor, an effect consistent with that of a positive allosteric modulator. In the rat Li-pilocarpine status epilepticus model, CYM2503, injected intraperitoneally, increased the latency to first electrographic seizure and the latency to first stage 3 behavioral seizure, decreased the latency to the establishment of status epilepticus, and dramatically decreased the mortality. In a Li-pilocarpine seizure model in mice, CYM2503 increased the latency to first electrographic seizure and decreased the total time in seizure. CYM2503 also attenuated electroshock-induced seizures in mice. Thus, CYM2503 provides a starting point for the development of anticonvulsant therapy using the galanin R2 receptor as target.
A Surface Femtosecond Two-Photon Photoemission Spectrometer for Excited Electron Dynamics and Time-Dependent Photochemical Kinetics
Authors: Ren Ze-feng , Zhou Chuan-yao , Ma Zhi-bo , Xiao Chun-lei , Mao Xin-chun , Dai Dong-xu , LaRue Jerry , Cooper Russell , M. Wodtke Alec , Yang Xue-ming
Published: July 2010

A surface femtosecond two-photon photoemission (2PPE) spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low energy photoelectrons are measured using a hemispherical electron energy analyzer with an imaging detector that allows us to detect the energy and the angular distributions of the photoelectrons simultaneously. A Mach–Zehnder interferometer was built for the time-resolved 2PPE (TR-2PPE) measurement to study ultrafast surface excited electron dynamics, which was demonstrated on the Cu(111) surface. A scheme for measuring time-dependent 2PPE (TD-2PPE) spectra has also been developed for studies of surface photochemistry. This technique has been applied to a preliminary study on the photochemical kinetics on ethanol/TiO2(110). We have also shown that the ultrafast dynamics of photoinduced surface excited resonances can be investigated in a reliable way by combining the TR-2PPE and TD-2PPE techniques.
Application of the SIMS Method in Studies of Cr Segregation in Cr‐Doped CoO: II, Depth Profiles
Authors: Bernasik Andrzej , Nowotny Janusz , Scherrer Stanislas , Weber Sylvian
Published: July 2010

Surface segregation‐induced depth profiles of Cr were determined for Cr‐doped CoO single crystals equilibrated at different temperatures (1373–1673 K) and oxygen partial pressures (102–105 Pa). It was shown that the shape of the depth profiles depends on both conditions of annealing and subsequent cooling procedure. It has been observed that during slow cooling of specimens from the condition of segregation equilibrium at elevated temperatures to the temperature of the experiment (room temperature), there is substantial change of the concentration profile involving desegregation of Cr (Cr diffusion from the surface to the bulk) resulting in its depletion. It has also been shown that the rate of the desegregation process (the process which results in a decrease of surface concentration) is slower than the lattice transport kinetics of Cr in CoO. It is concluded that the desegregation is rate‐controlled by the decomposition of a spinel‐type bidimensional surface structure which is formed at elevated temperatures as a result of Cr segregation.
Chevron‐Notched Toughness of Materials with Rising Fracture Resistance Curves
Authors: Zehnder Alan T. , Hui Chung‐Yuen , Rodeghiero Eric D.
Published: July 2010

The effect of rising resistance curves on the fracture tougness determined from chevron‐notched beam tests is estimated via a set of simple numerical calculations. It is shown that for materials with a rising resistance curve, the toughnesses determined by the peak load method and by the work of fracture method are both higher than the initiation toughness, and both depend on the sample size relative to the length over which the resistance curve increases. It is also found that the toughness based on the work of fracture is higher than that based on the peak load. Fracture toughness data obtained from tests of a nickel–alumina composite are discussed in light of the results of the numerical calculation.
Capacitor‐Discharge Joining of Oxide Ceramics
Authors: Turan Servet , Bucklow Ian A. , Wallach E. Robert
Published: July 2010

A capacitor‐discharge joining technique has been used to fabricate alumina–metal–alumina and zirconia–metal– zirconia joints using thin foils of aluminum, titanium, or amorphous Alx Niy Yz alloys as interlayers. The technique involves passing a high‐energy pulse through a conductive interlayer, so converting the interlayer into a liquid‐vapor “energized foil” which wets and bonds the pieces of ceramic being joined. The bond strengths of the joints were mea‐sured by shear testing which showed that the highest bond strengths for both alumina and zirconia substrates were obtained when an amorphous Alx Niy Yz interlayer was used. An investigation of the interfacial structure of the joints revealed that there is a distinct reaction layer between the ceramic substrate grains and the amorphous Alx Niy Yz interlayer.
Production of Silicon Carbide from Rice Husks
Authors: Gorthy Padmaja , G. Mukunda Pudukottah
Published: July 2010

This paper reports the formation of ß‐silicon carbide by the process of pyrolyzing rice husks (RH). The sequence of transformations and the mechanism of formation of crystalline silica, carbon, and silicon carbide from RH were investigated in detail. The structural evolution of silicon carbide particulates during the conversion process was critically examined by various techniques. Studies using X‐ray diffraction and infrared spectroscopic techniques revealed that a temperature of 1500°C is desirable for the completion of the reaction between RH silica and carbon, thereby leading to the formation of ß‐silicon carbide. Except for the gradual change in the morphology leading to the formation of dense crystals of ß‐SiCp, formation of alpha‐SiCp was not evidenced in the present studies. The fine particle size of ß‐SiC, formed at lower reaction temperatures, apparently precluded the transformation to alpha‐SiC.
Phase‐Diagram Studies in the La2O3–SrO–CaO–Mn3O4 System at 1200°C in Air
Authors: Majewski Peter , Epple Lars , Aldinger Fritz
Published: July 2010

The phase equilibria of the La2O3–SrO–CaO–Mn3O4 system in air at 1200°C has been studied. Under these conditions, eight univariant four‐phase equilbria were observed. Quaternary phases, as well as liquid phases, were not observed. Perovskite‐structure phases LaMnO3, SrMnO3, and CaMnO3 did not form complete solid solutions within the system.
Hot Isostatic Pressing of Chromium Nitrides (Cr2N and CrN) Prepared by Self‐Propagating High‐Temperature Synthesis
Authors: Hirota Ken , Takano Yoshihiko , Yoshinaka Masaru , Yamaguchi Osamu
Published: July 2010

Cr2N, CrN, and their mixtures (with desired fractions) have been prepared via self‐propagating high‐temperature synthesis (SHS) under a controlled nitrogen pressure, followed by hot isostatic pressing at 1300°C and 196 MPa under an atmosphere of argon gas. The combustion temperature increased as the nitrogen pressure increased. Single‐phase Cr2N was formed at 1040°C under a pressure of 0.18 MPa, and single‐phase CrN was formed at 1730°C under a pressure of 2 MPa. The mechanical properties of the dense nitride ceramics (99.2% of the theoretical density) have been examined; the Vickers hardness (11.2 GPa for CrN and 14.5 GPa for Cr2N) increased linearly as the fraction of Cr2N increased, whereas the fracture toughness (∼4.7 MPa·m1/2) and bending strength (∼355 MPa) are constant, regardless of the fraction of Cr2N/CrN.
Micro‐/Macroporous Ceramics from Preceramic Precursors
Authors: Schmidt Harald , Koch Dietmar , Grathwohl Georg , Colombo Paolo
Published: July 2010

Porous silicon oxycarbide (SiOC) ceramics in particular bulk and cellular structures are produced via polymer pyrolysis. By using optimal pyrolysis parameters (i.e., heating rate, maximum temperature) the addition of either solid fillers or chemically active additives is efficient in preventing the collapse of pore structure and controlling pore formation through decomposition. Fast pyrolysis can lead to crack formation and a loss of specific surface area at temperatures above 600°C, whereas slow pyrolysis is able to preserve mesopores up to 1200°C combined with high surface areas. These SiOC ceramics with bimodal pore size distribution are potential candidates for adsorption/separation processes under severe conditions.
Preparation of Lead Zirconate Titanate Thin Films Derived by Hybrid Processing: Sol‐Gel Method and Laser Ablation
Authors: Wang Zhan Jie , Karibe Isao , Maeda Ryutaro , Kokawa Hiroyuki
Published: July 2010

Thin films of Pb(Zr0.52Ti0.48)O3 (PZT) were prepared by hybrid processing (sol‐gel and excimer laser ablation) on Pt/Ti/SiO2/Si substrates. Crystalline phases and microstructures of the PZT films were investigated by X‐ray diffraction analysis and scanning electron microscopy, respectively. Electrical properties of the films were evaluated by measuring their P‐E hysteresis loops and dielectric constants. The temperature of postdeposition annealing in hybrid processing was lower than that in the case of direct film deposition by laser ablation on a Pt/Ti/SiO2/Si substrate. The preferred orientation of the films derived by hybrid processing could be controlled using the seeding layer deposited by the sol‐gel process. The films fabricated by hybrid processing consisted of the perovskite phase with a (111) preferred orientation and had good ferroelectric properties.
Autoimmune haemolytic anaemia with monoclonal IgM (κ) anti‐P cold autohaemolysins
Authors: Von Dem Borne A. E. G. Kr. , Mol J. J. , Joustra‐Maas N. , Pegels J. G. , Langenhuijsen M. M. A. C. , Engelfriet C. P.
Published: July 2010

A patient is described with immunoblastic non‐Hodgkin's lymphoma and autoimmune haemolytic anaemia of the cold autoantibody type. The autoantibodies were monoclonal IgM‐k cold haemagglutinins/haemolysins with blood‐group specificity, anti‐P. Red‐cell autoantibodies directed against blood‐group‐P antigen have until now only been detected, as polyclonal IgG antibodies, in paroxysmal nocturnal haemoglobinuria.
Circulating Granulocytic and Erythroid Progenitor Cells in Chronic Granulocytic Leukaemia
Authors: Goldman John M. , Shiota Fatih , Th'ng K. H. , Orchard Kim H.
Published: July 2010

Summary. We used a standard methyl cellulose method to assay erythroid progenitor cells in the blood of 35 patients with untreated CGL and of 18 normal controls. In 28 patients we simultaneously assayed granulocyte/nionocyte committed progenitor cells (CFU‐c) by an agar method. Circulating erythroid burst‐forming units (HFU‐e) in CGL wcre increased above normal by a factor of about 180; CFU‐c were increascd by a factor of about 9000. Both BFU‐e and CFU‐c numbers were linearly related to the total leucocyte count in individual patients but not to numbers of circulating blast cells. There was a positive correlation in individual patients between CFU‐c and BFU‐e numbers. Circulating BFU‐e and erythroid colony‐forming cells (CFU‐e) were unable to proliferate in vitro in the absence of erythropoietin. We conclude that erythroid progenitor cells are involved in the‘clonal expansion’that characterizes CGL, but apparently to a lesser extent than are granulocyte/monocyte progenitor cells.
Detection of Alpha Thalassaemia in Negro Infants
Authors: Higgs D. R. , Pressley L. , Clegg J. B. , Weatherall D. J. , Higgs S. , Carey P. , Serjeant G. R.
Published: July 2010

Summary. A prospective study of 2291 Negro infants in Jamaica showed that approximately 7% of them had detectable levels of Hb Bart's (γ4) in the neonatal period. The red cell indices, globin chain biosynthesis And restriction endonuclease mapping of DNA from these infants were used to determine the significance of Hb Bart's at birth. The results indicate that the genotypes αα/αα, —α/αα and —α/—α are associated with 0%, 0.1–2%, and greater than 2% Hb Bart's respectively. Although trace amounts of Hb Bart's may be associated with the genotype —α/αα this is not always the case and therefore haemoglobin analysis in the neonatal period cannot be used to diagnose this genotype with any certainty.
The Clinical Significance of Platelet‐Associated IgG: a Study on 298 Patients with Various Disorders
Authors: Mueller‐Eckhardt C. , Kayser W. , Mersch‐Baumert K. , Mueller‐Eckhardt C. , Breidenbach M. , And H.‐G. Kugel , Graubner M.
Published: July 2010

Summary. Platelet‐associated IgG (PAIgG) was studied by a quantitative platelet radioactive anti‐IgG test (PRAT) in 298 patients. At the time of investigation, 171 patients were thrombocytopenic (platelet count <100 × 109/1), 127 had normal platelet counts. Patients fell into the following disease categories: Idiopathic thrombocytopenic purpura (ITP) (N=81), possible ITP (19), acute ITP (9), systemic lupus erythematosus (22), autoimmune haemolytic anaemia of warm‐type (18), systemic blood disease (65), liver diseases (35), others (49). A significant elevation of PAIgG was found in all disease categories. There was a significant correlation between PAIgG and the reciprocal values of platelet counts for most disease groups. No relationship was discernible between PAIgG and hypergammaglobulinaemic states (serum IgG >1.8 g/l), Platelet survival studies (N=30) revealed that normal and increased values of PAIgG were associated with normal or shortened platelet mean life span. It is concluded that an elevated PAIgG is only one of several factors involved in the development of immunologically mediated thrombocytopenia.
I. EVIDENCE FOR THE VALIDITY OF THE ASSAY METHOD AND THE PHYSIOLOGICAL RELEVANCE OF ESTIMATES
Authors: Cotes P. Mary
Published: July 2010

A radioimmunoassay for erythropoietin (Ep) in human serum is described. Evidence of assay validity includes parallelism of dilution curves of the 2nd International Reference Preparation (IRP) (used as standard) with test sera, a fall in serum immunoreactive Ep following blood transfusion and an increase in serum immunoreactive Ep with increasing severity of anaemia except in anaemias associated with severe renal failure. The geometric mean estimate of serum immunoreactive Ep in 93 normal men and women was 13·3 miu/ml above the low erythropoietin serum pool used as baseline for the assay. Extra‐renal erythropoietin was detectable in the assay and gave a dilution curve parallel to the 2nd IRP.
The 5q – syndrome: an underdiagnosed form of macrocytic anaemia
Authors: Tinegate Hazel , Gaunt Lorraine , Hamilton Peter J.
Published: July 2010

Summary. Since the description in 1974 of the 5q– syndrome, only 29 cases have been reported. Over a 3 1/2 year period cytogenetic culture of bone marrow submitted from 344 patients being investigated for a blood disorder revealed nine patients with anomalies of chromosome 5. In five of these patients (samples arising from 37 patients being investigated for refractory macrocytic or aplastic anaemia) the 5q – syndrome was diagnosed. The clinical and haematological findings of this syndrome are reviewed and attention is drawn to the importance of reviewing megakaryocytic numbers and morphology in refractory macrocytic anaemia if the diagnosis is to be considered. The diagnosis is compatible with prolonged survival and establishing it prevents repeated and unnecessary investigation.
Dexamethasone enhances ‘CSA’ release and depresses ‘BPA’ release
Authors: Nissen C. , Moser Y. , Speck B. , Bürgin M. , Bendy H.
Published: July 2010

Summary. Dexamethasone 10−7m enhanced the release of granulocyte‐macro‐phage colony stimulating activity (GM‐CSA) by peripheral blood cells from 15 normals. In 16 patients with hypoplastic marrow failure this effect was more prominent, the release of GM‐CSA being increased up to 10‐fold by dexamethasone. Dose‐response curves of patient cell supernatants indicate that dexamethasone acts by abrogation of an inhibitor on CSA‐production.

Dexamethasone decreased the release of burst promoting activity (BPA) in all normals and most patients. We conclude that the interaction of glucocorticoid hormones with lymphocyte function results in positive and negative effects on haemopoiesis in vitro. Preliminary experiments in one patient suggest that the steroid effect in vivo correlates with GM‐CSA enhancement in vitro.
Circulating granulocyte and macrophage progenitor cells in primary and secondary myelofibrosis
Authors: Wang Jen C. , Cheung Chi P. , Ahmed Fakhiuddin , Steier William , Tobin Mark S.
Published: July 2010

Summary. Patients with primary myelofibrosis (PMF) and myelofibrosis secondary to carcinoma (SMF) were compared with regard to circulating granulocyte macrophage progenitor cells (CFU‐GM) using in vitro tissue culture techniques. Although increased numbers of CFU‐GM had previously been well documented in PMF, few patients with the secondary variety had been studied. Our data indicate that there is an increase in circulating CFU‐GM in patients with SMF but it is significantly lower than in those with PMF.

It is suggested that in both conditions disruption of the marrow microvascular system results in a release of CFU‐GM to the circulation. In PMF stem cell colonization of the spleen with its consequent myeloid metaplasia may be responsible for the additional increase in CFU‐GM. The determination of CFU‐GM numbers may provide additional data to help to distinguish PMF and SMF in atypical cases where the distinction is unclear.
Immune disorders in agnogenic myeloid metaplasia: relations to myelofibrosis
Authors: Rondeau E. , Solal‐Celigny P. , Dhermy D. , Vroclans M. , Brousse N. , Bernard J. F. , Boivin P.
Published: July 2010

Summary. Tests for a dysimmune state were done in an unselected group of 67 patients with agnogenic myeloid metaplasia (AMM). The results were compared to those of 56 patients with polycythaemia vera (PV). 75% of AMM patients versus 32% of PV patients had various abnormalities. The most frequent disorders among AMM patients were serum antinuclear and anti smooth muscle autoantibodies (10 3% each), a positive test for rheumatoid factor (21 7%), a polyclonal increase in serum immunoglobulin levels (46 8%) or a serum monoclonal component (9 7%), a positive direct Coombs’test (19%), an anti I autoantibody (30%). In AMM patients there was no relationship between age, sex, importance of splenic enlargement, time from diagnosis or treatment and the present of a dysimmunity.

Furthermore, in AMM patients, but also in PV patients, it seems that the more frequent and numerous these abnormalities the more severe is the myelofibrosis. Like other previous studies, these results suggest a lymphoid cell involvement in AMM and a role for these immune disorders in the pathogenesis of myelofibrosis.
Monoclonal antibodies against human platelet glycoprotein IIIa
Authors: Tetteroo P. A. T. , Lansdorp P. M. , Leeksma O. C. , Borne A. E. G. Kr. von dem
Published: July 2010

Summary. Two murine monoclonal antibodies specific for human platelets were prepared and characterized by immunofluorescence, immunoprecipitation and by studying their effect on platelet function.

Immunoprecipitation with lysates of normal platelets and platelets from a patient with Glanzmann's thrombasthenia revealed that the monoclonal antibodies were directed against glycoprotein GP IIIa.

One of these anti‐GP‐IIIa antibodies (C17) inhibited both ADP‐ and collagen‐induced platelet aggregation as well as ADP‐induced fibrinogen binding to platelets. The other anti‐GP‐IIIa antibody (C15) also caused a complete inhibition of aggregation with collagen. However, a small, and fully reversible, ‘primary wave’ was observed if the platelets were stimulated with ADP when platelet‐rich plasma was used. The ability to bind fibrinogen was unimpaired for platelets incubated with C15. These findings show that C15 and C17 probably recognize different determinants on GP IIIa. Neither of the monoclonal anti‐GP‐IIIa antibodies blocked the binding to Zwa‐positive platelets of human polyclonal anti‐Zwa antibodies. This implies that Zwa is different from the epitopes recognized by C15 and C17.
Different repopulation kinetics of erythroid (BFU‐E), myeloid (CFU‐GM) and T lymphocyte (TL‐CFU) progenitor cells after autologous and allogeneic bone marrow transplantation
Authors: Vellenga Edo , Sizoo Willemijn , Hagenbeek Anton , Löwenberg Bob
Published: July 2010

Summary. Marrow recovery of erythroid (BFU‐E). myeloid (CFIJ‐GM) and T‐lymphocyte (TL‐CFU) progenitor cells was studied at various time intervals after autologous bone marrow transplantation in 10 patients with acute myeloid leukaemia in remission. These data were compared with those in 14 recipients of T‐cell depleted allogeneic marrow grafts. The results indicate markedly different repopulation kinetics of BFIJ‐E. CFU‐GM and TL‐CFU after autologous and allogeneic bone marrow transplantation. Following auto‐grafting reduced numbers of BFU‐E and CFU‐GM were always present at 2 months after transplantation. Between 2–6 and 6–24 months a gradual increase occurred, although reduced BFU‐E and CFU‐GM values were stil noted in 50% of the cases in spite of normal bone marrow cellularity and restoration of peripheral blood counts. In contrast. in the allograft recipients normal BFU‐E numbers appeared within 2 months after transplantation. In addition, CFU‐GM values had become normal in 3 5% of the tests performed at 1 ‐2 months and respectively in 66% and 100% at 2–6 and 6–24 months. The recovery pattern of TL‐CFU differed from that of the other haemopoietic progenitor cells. TL‐CFU showed a fast recovery, i.e. within 1 month after autologous bone marrow transplantation which was much more rapid than that of BFU‐E and CFU‐GM. After allografting. however, TL‐CFU regenerated at a slower rate and reached normal levels between 2 and 6 months after transplantation. We suggest that the delayed restoration of myeloid and erythroid progenitor cells after autologous transplantation is related to a proliferative defect of the graft as a result of the preceding cytotoxic chemotherapy, the underlying malignant disease and/or cyropreservation. The slower recovery of the T lymphocyte precursors after allografting might be due to the immunological interactions between graft and host, the immuno‐suppressive therapy and/or the in vitro T cell depletion of the graft.
The measurement of the total volume of red cells in man: a non‐radioactive approach using biotin
Authors: Cavill I. , Trevett D. , Fisher J. , Hoy T.
Published: July 2010

Present methods for measuring red cell volume are based on the dilution of radioactively labelled cells. This precludes the investigation in neonates and pregnant women. We present a simple method for labelling red cells with biotin. These cells may be injected intravenously and subsequently detected using streptavidin‐FITC and flow‐cytometry. A comparison of the red cell volume estimated using both 51Cr and biotin labelled cells in 19 patients showed no consistent clinically significant difference between the two. This novel label appears to allow red volume to be reliably estimated without using radioactivity.
Haematopoietic and immunologic abnormalities in severe aplastic anaemia patients treated with anti‐thymocyte globulin
Authors: De Planque Mariet M. , Brand Anneke , Kluin‐Nelemans Hanneke C. , George Eernisse J. , Burgh Fred Van Der , Natarajan A. T. , Beverstock Geoffrey C. , Zwaan Ferdinand E. , Willemze and Roel , Van Rood Jon J.
Published: July 2010

Summary. Thirty‐five patients with severe aplastic anaemia (SAA) were extensively evaluated 0.3‐12.4 years (median 3.8) after anti‐thymocyte globulin (ATG) treatment. All but one were transfusion independent. Most patients revealed a normal Hb level and a granulocyte count over 1.5 × 109/1 but were still thrombocytopenic due to decreased platelet production. Lymphocytopenia and/or monocytopenia was found in about 30%. Two patients had a monocytosis. Although there was a great range in degree of recovery at various time intervals after ATG. patients tested more than 4 years after ATG tended to have higher cell counts. Lymphocyte counts correlated with the interval between ATG and evaluation, and with haematopoietic recovery. Qualitative abnormalities were found in all cell lines. Most patients showed a homogeneous macrocytic RBC population, and almost 50% a positive sucrose lysis test: only three patients showed evidence of haemolysis and only two of these showed a positive Ham test. Mean platetet volumes were reduced out of proportion to their number. Platelet function, determined by bleeding time and aggregometry, was impaired in over 30%. The granulocytic series showed a shift to the left in about 30%. Hypersegmentation and pseudo Pelger‐Huet anomaly were seen in some patients. Lymphocyte subset distribution in blood and bone marrow was within the normal range but absolute blood levels of CD4 cells in particular were slightly decreased, and tended to increase gradually with time after ATG. IgG and IgA levels were significantly decreased. In only one patient cytogenetic analysis of unstimulated bone marrow cells revealed an abnormal karyotype, but in eight of eight patients an increased sensitivity of lymphocytes to X‐rays was found. These data suggest impairment at the level of the very early haematopoietic progenitor cell in all patients up to 10 years after ATG. Since similar findings have been reported in clonal (pre‐)malignant disease, SAA, improved after ATG treatment, might be prone to clonal (malignant) evolution.
Decline of blood haemoglobin in the aged: a longitudinal study of an urban Swedish Population from age 70 to 81
Authors: Nilsson‐Ehle Herman , Jagenburg Rudolf , Landahl Sten , Svanborg Alvar , Westin Jan
Published: July 2010

Summary Blood haemoglobin (Hb) and telated components were determined in a representative sample (n=973, 449 men and 524 women) of a 70‐yar‐old population. reinvestigated at age 75. 79 and 81. At age 81. 145 men and 259 wonem remained in the study. Longitudinal analysis demonstrated a significant decline in Hb concentration with advancing age, in the total study groups as well as in subsamples remaining after exclusions due to disease. The mean annual decline from age 70 to 81 in a subsample without definable disorders was in men 0.063 g/g/dl. in women 0.035 g/dl. There was a similar decline among subjects with high, intermediate or low Hb concentrations during the study. Only part of the observed intrainadividual variations could be explainedbny factors other than age.
Molecular basis of clinical and morphological heterogeneity in hereditary elliptocytosis (HE) with spectrin αI variants
Authors: Lecomte M. C. , Garbarz M. , Gautero H. , Bournier O. , Galand C. , Boivin P. , Dhermy D.
Published: July 2010

Summary. The impaired ability of spectrin dimers to self‐associate into tetramers is one of the most frequent defects associated with hereditary elliptocytosis (HE) and its more serious form, hereditary pyropoikylocytosis (HPP). We previously described four proteic variants of the spectrin (Sp) a1 tryptic domain associated with the Sp dimer self‐association defect (Sp α1/78, Sp α1/74, Sp α1/65, Sp α1/46 variants). Following the characterization of proteic variants, genomic molecular defects were identified and most of the mutations appeared to lie either in or near the self‐association site, i.e. in the αI tryptic domain or in the βI tryptic domain.

The clinical severity of these different mutations varies considerably and ranges from asymptomatic to severe hae‐molytic disease such as in heterozygous HPP patients and in some homozygous HE patients.

Studies of 113 patients from 61 HE families showed a correlation among parameters and showed which factors modulate the clinical expression of the molecular defect. Our analysis indicated that the clinical expression was directly correlated with the severity of the spectrin dimer self‐association defect as evaluated by the increase in the Sp dimmer percentage found in the 4°C extract. A critical threshold of 40–50% of unassembled Sp dimer was determined; above that, patients exhibited severe haemolysis requiring splenec‐tomy. The percentage of Sp dimer depends, in turn, on two factors: (i) the nature of the variant in relation to the position of the mutation versus the tetramerization site: (ii) the relative amount of mutant spectrin present in the membrane (ranging from 15% to 80% in heterozygous patients). As for the severity of haemolysis, the ghost mechanical stability to shear stress, as measured by ektacyometer, was also found to depend on the Sp dimer self‐association defect. In contrast, the decrease in erythrocyte deformability was not related to the amount of unassembled Sp dimer but appeared to be correlated with the amount of mutant spectrin whatever the variant.

Concerning erythrocyte morphology and the number of elliptocytes, the Sp α1/65 variant appears to be the most ‘elliptocytogenic’ variant, indicating that erythrocyte shape abnormality is not linked to the Sp dimer self‐association defect.
Clonal analysis of peripheral blood and haemopoietic colonies in patients with aplastic anaemia and refractory anaemia using the polymorphic short tandem repeat on the human androgen‐receptor (HUMARA) gene
Authors: Anan Kazuaki , Ito Maki , Misawa Mahito , Ohe Yokiko , Kai Shunro , Kohsaki Masatoshi , Hara Hiroshi
Published: July 2010

The clonalities in white blood cells (WBC) of blood and nucleated bone marrow cells from patients with refractory anaemia and aplastic anaemia were examined by polymerase chain reaction (PCR) methods using the polymorphic short tandem repeat (STR) on the human androgen‐receptor gene (HUMARA). Peripheral blood samples were obtained from 12 female patients, six with aplastic anaemia (AA) and six with refractory anaemia (RA). Peripheral blood was fractionated into granulocytes, lymphocytes, T lymphocytes and B lymphocytes. DNA was extracted from each fraction. Bone marrow samples were obtained from seven female patients (three with AA and four with RA). Sorted CD34 positive cells were cultured in a semisolid culture system. DNA was extracted from a 14‐day haemopoietic colony. The clonal pattern was assessed using HUMARA gene STR polymorphism and the differential methylation pattern of nearby cytosine residues by PCR methods. Four of six (67%) AA and two of six (33%’RA patients had a monoclonal proliferating pattern in their granulocytes. The ratio of the numbers of minority colonies per majority colonies (m/M ratio) was examined for seven patients (three AA and four RA). In patients who had a clonal haemopoietic pattern in peripheral WBC the ratio was under 0.4 but not zero. In contrast, patients exhibiting a polyclonal pattern had an m/M ratio above 0.8. We concluded that some normal or heterogenous haemopoietic clones, not only MDS but also AA, may remain in the bone marrow, although almost all colonies were derived from a single pathogenic clone when the clonality pattern exhibited monoclonality in peripheral blood analysis.