bluuebunny/crossref_metadata_2025 huggingface dataset:
Limited efficacy of pentoxifylline as anti-inflammatory agent in experimental pneumococcal meningitis
Authors: ZYSK G , BRÜCK W , FISCHER F R , MÄDER M , RIECKMANN P , NAU R
Published: July 2010

Dexamethasone appears to show some adverse side-effects as adjunctive anti-inflammatory agent in bacterial meningitis. For this reason, we tested the anti-inflammatory and neuroprotective effect of pentoxifylline administered 15 min before starting antibiotic treatment with ceftriaxone (n = 10) versus antibiotic therapy alone (n = 9) in the rabbit model of pneumococcal meningitis. Pentoxifylline lowered the medians of leucocyte density, tumour necrosis factor-alpha (TNF-α) and lactate in the cerebrospinal fluid (CSF), but only leucocyte migration into the subarachnoid space was significantly inhibited 8 h after initiation of therapy (P = 0.01). CSF protein, brain water content, and the entry of ceftriaxone into CSF were not influenced by pentoxifylline. The density of neuronal apoptoses in the dentate gyrus was slightly lower in animals receiving pentoxifylline than in those treated with ceftriaxone only. The median concentration of neuron-specific enolase in CSF was lower in the pentoxifylline-treated group, but the difference was not significant. In conclusion, pentoxifylline showed some anti-inflammatory activity in pneumococcal meningitis, but the substance failed significantly to reduce neuronal damage.
Subunits fold at position-dependent rates during maturation of a eukaryotic RNA virus
Authors: Matsui Tsutomu , Lander Gabriel C. , Khayat Reza , Johnson John E.
Published: July 2010

Effective antiviral agents are difficult to develop because of the close relationship between the cell biology of the virus and host. However, viral capsid maturation, the in vivo process where the particle transitions from a noninfectious provirion to an infectious virion, is an ideal process to interrupt because the provirion is usually fragile and the conversion to the virion often involves large conformational changes and autocatalytic chemistry that can be hampered by small molecules. The
Nudaurelia capensis ω
virus (NωV) is one of the few eukaryotic viruses where this process can be investigated in vitro with a variety of biophysical methods, allowing fundamental chemical and structural principles of the maturation to be established. It has a
T
 = 4 quasi-equivalent capsid with a dramatic maturation pathway that includes a particle size reduction of 100 Å and an autocatalytic cleavage. Here we use cryo-EM and difference maps, computed at three time points following maturation initiation, to show that regions of NωV subunit folding are maturation dependent and occur at rates determined by their quasi-equivalent position in the capsid, explaining the unusual kinetics of the maturation cleavage. This study shows that folding is rapid and peptide chain self-cleavage occurs early for subunits adjacent to 3-fold and 5-fold icosahedral symmetry elements and that folding is slower in regions where molecular switches are required for the formation of the proper interfacial contacts. The results connect viral maturation to the well-studied assembly-dependent folding that occurs in the formation of cellular complexes.
Speaker–listener neural coupling underlies successful communication
Authors: Stephens Greg J. , Silbert Lauren J. , Hasson Uri
Published: July 2010

Verbal communication is a joint activity; however, speech production and comprehension have primarily been analyzed as independent processes within the boundaries of individual brains. Here, we applied fMRI to record brain activity from both speakers and listeners during natural verbal communication. We used the speaker's spatiotemporal brain activity to model listeners’ brain activity and found that the speaker's activity is spatially and temporally coupled with the listener's activity. This coupling vanishes when participants fail to communicate. Moreover, though on average the listener's brain activity mirrors the speaker's activity with a delay, we also find areas that exhibit predictive anticipatory responses. We connected the extent of neural coupling to a quantitative measure of story comprehension and find that the greater the anticipatory speaker–listener coupling, the greater the understanding. We argue that the observed alignment of production- and comprehension-based processes serves as a mechanism by which brains convey information.
MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output
Authors: O'Connell Ryan M. , Chaudhuri Aadel A. , Rao Dinesh S. , Gibson William S. J. , Balazs Alejandro B. , Baltimore David
Published: July 2010

The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output.
FoxM1 regulates re-annealing of endothelial adherens junctions through transcriptional control of β-catenin expression
Authors: Mirza Muhammad K. , Sun Ying , Zhao Yidan D. , S.K. Potula Hari-Hara , Frey Randall S. , Vogel Steven M. , Malik Asrar B. , Zhao You-Yang
Published: July 2010

Repair of the injured vascular intima requires a series of coordinated events that mediate both endothelial regeneration and reannealing of adherens junctions (AJs) to form a restrictive endothelial barrier. The forkhead transcription factor FoxM1 is essential for endothelial proliferation after vascular injury. However, little is known about mechanisms by which FoxM1 regulates endothelial barrier reannealing. Here, using a mouse model with endothelial cell (EC)-restricted disruption of FoxM1 (FoxM1 CKO) and primary cultures of ECs with small interfering RNA (siRNA)-mediated knockdown of FoxM1, we demonstrate a novel requisite role of FoxM1 in mediating endothelial AJ barrier repair through the transcriptional control of β-catenin. In the FoxM1 CKO lung vasculature, we observed persistent microvessel leakage characterized by impaired reannealing of endothelial AJs after endothelial injury. We also showed that FoxM1 directly regulated β-catenin transcription and that reexpression of β-catenin rescued the defective AJ barrier–reannealing phenotype of FoxM1-deficient ECs. Knockdown of β-catenin mimicked the phenotype of defective barrier recovery seen in FoxM1-deficient ECs. These data demonstrate that FoxM1 is required for reannealing of endothelial AJs in order to form a restrictive endothelial barrier through transcriptional control of β-catenin expression. Therefore, means of activating FoxM1-mediated endothelial repair represent a new therapeutic strategy for the treatment of inflammatory vascular diseases associated with persistent vascular barrier leakiness such as acute lung injury.
Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U
Authors: Tsai Kuen-Jer , Yang Chun-Hung , Fang Yen-Hsin , Cho Kuan-Hung , Chien Wei-Lin , Wang Wei-Ting , Wu Tzu-Wei , Lin Ching-Po , Fu Wen-Mei , Shen Che-Kun James
Published: July 2010

TDP-43 is a multifunctional DNA/RNA-binding factor that has been implicated in the regulation of neuronal plasticity. TDP-43 has also been identified as the major constituent of the neuronal cytoplasmic inclusions (NCIs) that are characteristic of a range of neurodegenerative diseases, including the frontotemporal lobar degeneration with ubiquitin+ inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). We have generated a FTLD-U mouse model (CaMKII-TDP-43 Tg) in which TDP-43 is transgenically overexpressed in the forebrain resulting in phenotypic characteristics mimicking those of FTLD-U. In particular, the transgenic (Tg) mice exhibit impaired learning/memory, progressive motor dysfunction, and hippocampal atrophy. The cognitive and motor impairments are accompanied by reduced levels of the neuronal regulators phospho–extracellular signal-regulated kinase and phosphorylated cAMP response element-binding protein and increased levels of gliosis in the brains of the Tg mice. Moreover, cells with TDP-43+, ubiquitin+ NCIs and TDP-43–deleted nuclei appear in the Tg mouse brains in an age-dependent manner. Our data provide direct evidence that increased levels of TDP-43 protein in the forebrain is sufficient to lead to the formation of TDP-43+, ubiquitin+ NCIs and neurodegeneration. This FTLD-U mouse model should be valuable for the mechanistic analysis of the role of TDP-43 in the pathogenesis of FTLD-U and for the design of effective therapeutic approaches of the disease.
Laser-induced Fluorescence Spectrum of CoS Between 15200 and 19000 cm−1
Authors: Zhen Jun-feng , Wang Li , Qin Cheng-bing , Zhang Qun , Chen Yang
Published: July 2010

Laser-induced fluorescence excitation spectra of jet-cooled CoS molecules have been recorded in the energy range of 15200–19000 cm−1. Five transition progressions have been reported for the first time, the assignments of these progressions have been derived from a rotational analysis of vibronic bands and they are determined to be [15.58]4Δ7/2-X4Δ7/2, [16.02]4Δ7/2-X4Δ7/2, [16.50]4Δ7/2-X4Δ7/2, [17.80]4Π5/2-X4Δ7/2, and [18.00]4Δ7/2-X4Δ7/2 transitions. In addition, under the supersonic jet condition the fluorescent lifetimes of these vibronic states were measured by exponentially fitting the fluorescence decay. Based on the observed spectra and the measured lifetimes of the vibronic states, the newly identified electronic states are discussed.
A COMPILATION OF PHASE‐RULE DIAGRAMS OF INTEREST TO THE CERAMIST AND SILICATE TECHNOLOGIST*
Authors: Hall F. P. , Insley Herbert
Published: July 2010

This paper is a compilation of phase‐rule diagrams, principally of silicates and the refractory oxides, that may be useful to the ceramist and the silicate technologist. The text of the paper includes definitions of terms used in discussion of the Phase Rule, a description of methods used in the study of systems at high temperatures, and an interpretation of Phase‐Rule diagrams for systems with one or more components.
FACTORS INVOLVED IN PRODUCTION OF THIN WALL TILE*
Authors: Heystek Hendrik , Campbell R. M.
Published: July 2010

Abstract

A study was made relative to the dry pressing of wall tile having a thickness of 3/16 in. Three bodies, a high talc, a high pyrophyllite, and a regular body were studied. The water content was kept constant and the forming pressures were varied from 1000 to 3000 lb. per sq. in. The bodies were fired to cones 4, 6, and 8. The bisque tile were tested for thermal expansion, warpage, absorption, shrinkage, impact strength, transverse strength, and moisture expansion. The glazed tile were tested for warpage, impact resistance, and moisture expansion.

The results showed that satisfactory thin wall tile could be made from all bodies, the high‐pyrophyllite body indicating the greatest promise. It was found that pressing pressures had definite effects on impact strength, warpage, shrinkage, and thermal expansion.
Reactive Infiltration of Aluminum into Molybdenum Disilicide Preform
Authors: Ramasesha Sheela K. , Shobu Kazuhisa
Published: July 2010

Aluminum has been reactively infiltrated into a molybdenum disilicide preform with relative densities of 40% and 85%. The resultant compact is found to contain Mo(Al,Si)2 particles surrounded by aluminum metal; 14 to 18 at.% of aluminum reacted with MoSi2 irrespective of the infiltration temperature and time.
Preparation and Dielectric Properties of Low‐Temperature‐Sinterable (Zr0.8Sn0.2)TiO4 Powder
Authors: Han Kyoung R. , Jang Jin‐Wook , Cho Seo‐Yong , Jeong Dae‐Yong , Hong Kug‐Sun
Published: July 2010

Low‐temperature‐sinterable (Zr0.8Sn0.2)TiO4 powders were prepared using 3 mol% Zn(NO3)2 additive and then compared with powders prepared using 3 mol% ZnO additive and no additives. Sintering at 1200°C for 2 h produced a dielectric ceramic with ρ= 98.6% of theoretical density (TD), ɛr= 38.4, Q×f (GHz) = 42000, and τf=−1 ppm/°C. Sintering at 1250°C resulted in an excellent dielectric with ρ= 99% of TD, epsilonr= 40.9, Q×f (GHz) = 49000, and τf=−2 ppm/°C. Scanning electron microscopy showed a microstructure with grains measuring 0.5 to 1 μm, and transmission electron microscopy revealed secondary phase in the grain boundaries.
In‐Flight Nitridation of Molybdenum Disilicide Powders by an Induction Plasma
Authors: Fan Xiaobao , Ishigaki Takamasa , Suetsugu Yasushi , Tanaka Junzo , Sato Yoichiro
Published: July 2010

The in‐flight nitridation of MoSi2 powder particles was attempted in an argon‐nitrogen induction plasma, with and without tail gas quenching. The inductive power level, reactor pressure, plasma‐gas composition, and quantity of quench gas, as well as the species of quench gas, were investigated to obtain substantial nitridation of the MoSi2 powder particles. Under investigated conditions, ∼2.8 wt% of nitrogen was incorporated into the MoSi2 powder particles.
Influence of Peptization and Ethanol Washing on the Pore‐Structure Evolution of Sol‐Gel‐Derived Alumina Catalyst Supports
Authors: Nair Jalajakumari , Nair Padmakumar , Van Ommen Jan G. , Ross Julian R. H. , Burggraaf Anthonie J. , Mizukami Fujio
Published: July 2010

Alkoxide‐derived boehmite precipitates were subjected to different post‐precipitation treatments to obtain a peptized sol, an unpeptized slurry, and an ethanol‐washed gel precipitate. These materials were dried further to obtain the corresponding gels. Changes in the surface area, porosity, and pore size with temperature and the phase‐transformation behavior from gamma‐alumina to alpha‐alumina were studied using X‐ray diffractometry, differential scanning calorimetry, and physical adsorption/desorption measurements. Gels that were obtained from the peptized sol retained the lowest porosity, in comparison to the ethanol‐washed gel and the gel that was prepared from the aqueous slurry.
Crystal Growth and Electrical Properties of Pb((Zn1/3Nb2/3)0.91Ti0.09)O3Single Crystals Produced by Solution Bridgman Method
Authors: Harada Kouichi , Shimanuki Senji , Kobayashi Tsuyoshi , Saitoh Shiroh , Yamashita Yohachi
Published: July 2010

Piezoelectric Pb((Zn1/3Nb2/3)0.91Ti0.09)O3(PZNT 91/9) single crystals 40 mm in diameter were successfully grown from solution by the Bridgman method with a PbO flux. The crystals were grown in a platinum crucible heated to 1130°C. Growth rate was 0.35 mm/h. The obtained crystals were ~40 mm in diameter 20 mm in length and were a rust‐brown color. The Curie temperature,TC, ranged from 175° to 185°C, and the dielectric constant before poling at room temperature was 2000‐8900 within a wafer. After electrical poling, specimens had electromechanical coupling coefficients in rectangular bar mode,k33´, of 79%‐88%, which were larger than for PZT ceramics (k33´< 70%). These PZNT 91/9 single crystals grown by the Bridgman process satisfy the requirements for array‐type transducers used in echocardiographic equipment. Results confirm that the Bridgman method is useful for mass‐producing large crystals of PZNT 91/9.
Silica and Magnesia Dopant Distributions in Alumina by High‐Resolution Scanning Secondary Ion Mass Spectrometry
Authors: Gavrilov Konstantin L. , Bennison Stephen J. , Mikeska Kurt R. , Chabala Jan M. , Levi‐Setti Riccardo
Published: July 2010

Trace SiO2 and MgO additive distributions in sintered alumina have been studied using high‐resolution scanning secondary ion mass spectrometry (SIMS). When doped with each additive individually, evidence is seen for both strong silicon segregation to grain boundaries (Cgb/Cgrain similar/congruent 300) in SiO2‐doped alumina and strong magnesium segregation to grain boundaries (Cgb/Cgrain similar/congruent 400) in MgO‐doped alumina. When codoped with both SiO2and MgO, segregation of both ions to grain boundaries is reduced by a factor of 5 or more over single doping. The additive concentrations increase proportionally in the grains, and both dopants become more uniformly distributed throughout the bulk. It is concluded that codoping with these additives increases their mutual bulk solid solubility and decreases their interfacial segregation over single doping. The beneficial effect of MgO additions in controlling microstructure development in alumina and improving corrosion resistance to aqueous HF stems from its ability to redistribute silicon ions from grain boundaries into the bulk.
Microwave Properties of Ba2Ti9O20 Doped with Zirconium and Tin Oxides
Authors: Lin Wen‐Yi , Speyer Robert F. , Hackenberger Wesley S. , Shrout Thomas R.
Published: July 2010

The effects of solid‐solution additives, their concentration, and the thermal processing schedule on the microstructure evolution and microwave properties of Ba2Ti9O20 were studied. The solubility of tin in Ba2Ti9O20 was higher than that of zirconium. Both elements facilitated the formation of phase‐pure Ba2Ti9O20 resonators. Ba2Ti9O20 formed most easily with low dopant concentrations (0.82 mol%) (most impressively for ZrO2 substitutions). Extended heat treatment (16 h versus 6 h at a temperature of 1390°C) resulted in volatilization of the grain‐boundary liquid phase, which leads to more‐porous resonators that have correspondingly lower permittivities. Increasing the dopant concentration resulted in minor increases in the quality factor; doping with zirconium led to slightly higher values (a maximum of 13900 at a frequency of 3 GHz). Increasing the measurement temperature degraded the quality factor (most precipitously for BaTi4O9). The temperature coefficient decreased as the ZrO2 substitution increased but was largely unaffected by the SnO2 concentration. Excess TiO2 in a batch with no other dopants demonstrated degraded microwave properties.
Elastic Properties and Structure of Interpenetrating Boron Carbide/Aluminum Multiphase Composites
Authors: Torquato Salvatore , Yeong Christofer L. Y. , Rintoul Mark D. , Milius David L. , Aksay Ilhan A.
Published: July 2010

We study the elastic moduli and structure of boron carbide/aluminum (B4C/Al) multiphase composites using rigorous bounding and experimental characterization techniques. We demonstrate that rigorous bounds on the effective moduli are useful in that they can accurately predict (i) the effective elastic moduli, given the phase moduli and volume fractions, or (ii) the phase moduli (volume fractions), given the effective moduli and phase volume fractions (moduli). Using the best available rigorous bounds on the effective elastic moduli of multiphase composites involving volume‐fraction information, we are able to predict the bulk and shear moduli of the Al4BC phase, a reaction product that forms during heat treatment. These theoretical predictions are in very good agreement with recent experimental measurements of the moduli of the Al4BC phase. Moreover, we evaluate more‐refined bounds involving three‐point structural correlation functions by extracting such information from an image of a sample of the B4C/Al composite. Although experimental data for the effective moduli are unavailable for this sample, our predictions of the effective moduli based on three‐point bounds should be quite accurate.
Segregation in Yttrium Aluminum Garnet: I, Experimental Determination
Authors: Brown Kelly R. , Bonnell Dawn A.
Published: July 2010

Single crystals of yttrium aluminum garnet (YAG) that were doped with various cations were annealed in air at different temperatures for varying amounts of time. Dopants were chosen to probe the effect of size, charge, and site occupancy on surface segregation. Of the dopants that were chosen for the study (calcium, silicon, neodymium, chromium, and strontium), calcium was the only one that consistently segregated upon annealing in air. Calcium enrichment to the (111) surface was measured using Auger electron spectroscopy, and the segregation enthalpy was determined to be δHseg≈−32 ± 10 kJ/mol. Enrichment occurred according to variations in valence, as opposed to variations in size; therefore, it is suggested that surface segregation is electrostatically driven. The results indicate that aliovalent substituents could be used for interface property tailoring, whereas isovalent dopants would not be useful.
CVD Mullite Coatings in High‐Temperature, High‐Pressure Air–H2O
Authors: Haynes J. Allen , Lance Michael J. , Cooley Kevin M. , Ferber Mattison K. , Lowden Richard A. , Stinton David P.
Published: July 2010

Crystalline mullite was deposited by chemical vapor deposition (CVD) onto SiC/SiC composites overlaid with CVD SiC. Specimens were exposed to isothermal oxidation tests in high‐pressure air + H2O at 1200°C. Unprotected CVD SiC formed silica scales with a dense amorphous inner layer and a thick, porous, outer layer of cristobalite. Thin coatings (∼2 μm) of dense CVD mullite effectively suppressed the rapid oxidation of CVD SiC. No microstructural evidence of mullite volatility was observed under these temperature, pressure, and low‐flow‐rate conditions. Results of this preliminary study indicate that dense, crystalline, high‐purity CVD mullite is stable and protective in low‐velocity, high‐pressure, moisture‐containing environments.
Evidence of Nearest‐Neighbor Ordering in Wet‐Processed Zirconia–Nickel Composites
Authors: Pecharromán Carlos , López‐Esteban Sonia , Bartolomé José F. , Moya José S.
Published: July 2010

Monolithic zirconia–nickel (ZrO2/Ni) cermets have been prepared by a wet‐processing method with nickel volume concentrations of 16%–40%. Microstructural analysis performed on scanning electron microscopy images has revealed evidence of a partial ordering of metallic particles inside the ceramic matrix. This ordering does not appear in mullite/molybdenum cermets. Complex impedance measurements have shown that the percolation threshold of ZrO2/Ni cermets appears at a filling factor (fc) of 0.34, exceeding the theoretical value (fc= 0.16), as a consequence of its microstructural order. Electrical measurements display the expected increase of capacity near the percolation threshold. These results open the possibility to design new devices with the appealing electric, magnetic, and mechanical properties that are predicted by the percolation theory.
Thermal Shock Resistance of Silicon Nitrides Using an Indentation–Quench Test
Authors: Lee Seung Kun , Moretti James D. , Readey Michael J. , Lawn Brian R.
Published: July 2010

Thermal shock resistance of silicon nitrides is investigated using an indentation–quench method. Four commercially available silicon nitrides with different microstructures are investigated. The extension of Vickers radial cracks is measured as a function of quenching temperature for each material, up to the critical temperature for failure. An indentation fracture mechanics analysis is used to account for the crack responses, with due allowance for R‐curve behavior. The analysis confirms the important role of microstructure in thermal shock resistance.
Systematic review: Helicobacter pylori and the risk of upper gastrointestinal bleeding risk in patients taking aspirin
Authors: Fletcher E. H. , Johnston D. E. , Fisher C. R. , Koerner R. J. , Newton J. L. , Gray C. S.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 831–839

Background  Aspirin is widely used to modify the risk of recurrent vascular events. It is, however, associated with increased upper gastrointestinal bleeding risk. The influence of Helicobacter pylori on this risk is uncertain.

Aim  To determine the influence of H. pylori on upper gastrointestinal bleeding risk in patients taking aspirin.

Methods  MEDLINE and EMBASE databases were searched. All studies providing data regarding H. pylori infection in adults taking aspirin and presenting with upper gastrointestinal bleeding were included.

Results  A total of 13 studies that included 1 case–control, 10 cohort studies and 2 randomized‐controlled trials (RCTs) were analysed. The case–control study (n = 245) determined H. pylori to be a significant independent risk factor for upper gastrointestinal bleeding. The cohort studies were heterogeneous, varying in inclusion criteria, doses and duration of aspirin used, mode of H. pylori testing and causative GI pathology considered. Comprising 5465 patients, H. pylori infection was tested for in 163 (0.03%) aspirin users with upper gastrointestinal bleeding. The RCTs yielded no significant results.

Conclusions  The current data are not sufficient to allow meta‐analyses. The widely held belief that H. pylori is a risk factor for upper gastrointestinal bleeding in regular aspirin users is not supported by the very limited evidence available.
Congenital Dyserythropoietic Anaemia Type I: Absence of Clonal Expression in the Nuclear Abnormalities of Cultured Erythroblasts
Authors: Vainchenker W. , Guichard J. , And J. Bouguet. , Breton‐Gorius J.
Published: July 2010

Summary. Erythroid colonies derived from the circulating early erythroid precursor (BFU‐E) of a patient with congenital dyserythropoietic anaemia type I (CDA I) have been grown in plasma clot and studied by electron microscopy. The number of circulating BFU‐E was in the normal range with a roughly normal appearance at the light microscopic level. However, investigation of individual colonies by electron microscopy has always shown a mixture of normal and abnormal erythroblasts exhibiting the typical nuclear aberrations found in vivo. The proportion of normal erythroblasts varied from one colony to another. After the release of the cells from the clot in order to permit new cellular interactions, macrophages were observed to phagocytose abnormal erythroblasts but also a few erythroblasts with normal nuclei. These findings demonstrate that CDA I is a disorder which results from a defective erythroid stem cell but that the progeny of each BFU‐E may vary considerably in the extent to which they express the morphological defects. Based on studies of cultures of BFU‐E, similar conclusions were previously made for CDA 11.
The Abilities of Human Blood Platelets to Bind Extracellular Calcium and to be Aggregated by Adenosine Diphosphate are Related
Authors: Taylor Patricia M. , Heptinstall S.
Published: July 2010

Summary. A technique is described for preparing platelet rich plasma containing a very low level of extracellular calcium. Using this Ca‐depleted PRY it has been possible to demonstrate that extraplatelet calcium is in equilibrium with a small amount of calcium that is bound to the platelet surface. When Ca‐depleted PRP is incubated at 37°C the platelets lose their ability to bind calcium. At the same time they lose their ability to aggregate. It is likely that the binding of calcium to the platelet surface is a prerequisite for ADP‐induced aggregation.
Migration of Entire Megakaryocytes through the Marrow‐Blood Barrier
Authors: Tavassoli Mehdi , Aoki Makoto
Published: July 2010

Summary. Electron microscopic evidence is presented to indicate that entire megakaryocytes traverse the marrow‐blood barrier and enter the circulation. Passage occurs through apertures of 6 μm in diameter, located in the parajunctional areas of the marrow sinus endothelium. Serial sectioning indicates that these apertures are transendothelial rather than interendothelial. The cytoplasm of these megakaryocytes form sinuating elongated projections which may release their platelets in the sinus lumen or when reaching the pulmonary circulation. In the extravascular compartments, megakaryocytes are preferentially located in the subendothelial region. In this location they can send numerous organelle‐free projections into the lumen. These projections distinguishable from less numerous organelle‐containing projections could serve to ‘anchor’ the cell to the endothelium. They could also serve to ‘monitor’ the circulation and to receive information as to the requirement of body for platelet formation.
Quantitation of Red Blood Cell‐bound C3d in Normal Subjects and Random Hospitalized Patients
Authors: Chaplin H. , Nasongkla M. , Monroe M. C.
Published: July 2010

Summary. A sensitive radiolabelled anti‐antiglobulin method was devised and applied to quantitating red blood cell‐bound C3d (RBC‐C3d) in samples from 174 normal blood donors. C3d was demonstrable on all RBC examined; 98% of values fell over a broad range, with the highest values being approximately 3·5 × the lowest values (equivalent to 50–160 molecules of C3d per cell). RBC‐C3d did not correlate with sex or age (over 18–65 years); indirect evidence suggests that values for the paediatric age group will fall in the same normal range. Studies on samples obtained weekly for 10–12 weeks from six adult males and six adult females indicated stable levels of RBC‐C3d for individual subjects; i.e. high normals, mid normals and low normals remained in their characteristic range levels over the period of observation. For comparison, RBC‐C3d was measured in samples from 313 randomly selected hospitalized adult patients. 33% of the values were above the normal range; 8% were elevated to a level likely to have been detectable by a direct anti‐C3d antiglobulin test. The great majority of elevated values occurred in patients not ordinarily considered to have autoimmune conditions. The results provide background for studies of the aetiology and significance of RBC‐C3d in health and disease.
Development of the Accelerated Phase during Ascorbic Acid Therapy in Chediak‐Higashi Syndrome and Efficacy of Colchicine on its Management
Authors: Saitoh Hiroharu , Komiyama Atsushi , Norose Noboru , Morosawa Hironori , Akabane Taro
Published: July 2010

Summary. Clinical studies were done on a patient with Chediak‐Higashi syndrome (CHS) with special emphasis on the accelerated phase. In order to obtain further information on the accelerated phase, haematopoiesis was studied by bone marrow culture techniques. The patient was placed on ascorbic acid therapy but she entered the accelerated phase, although the therapy improved in vitro neutrophil function to some extent. Administration of microtubulytic drugs such as vincristine, vinblastine and colchicine was effective in the management of the accelerated phase. Numbers of macrophage‐granulocytic (CFU‐C) and erythroid (CFU‐E) progenitor cells were markedly decreased or absent during the accelerated phase, being another indicator of the accelerated phase.
Characterization of a Developmentally Early Macrophage Progenitor Found in Normal Mouse Marrow
Authors: Baines Paul , Bol Simon , Rosendaal Martin
Published: July 2010

Summary. In tissue culture high proliferation potential colony forming cells (HPP‐CFC, Bradley & Hodgson, 1979) formed large colonies in which macrophages predominated. Granulocyte/macrophage colony forming cells (GM‐CFC, Bradley & Metcalf, 1966) formed smaller colonies of granulocytes and macrophages. We compared HPP‐CFC from normal adult mouse bone marrow with GM‐CFC from the same source. We found that HPP‐CFC differed from GM‐CFC in the following ways: (1) HPP‐CFC formed larger colonies containing more than 5 × 104 cells. (2) They required spleen conditioned medium (Metcalf & Johnson, 1978) as well as pregnant mouse uterine extract (PMUE, Bradley et al, 1971) as stimulants. (3) Only 9% of HPP‐CFC were killed by the phase specific drug hydroxyurea. 36–55% of GM‐CFC were killed by the same treatment. (4) The modal density of HPP‐CFC was 1·070 g/cm3. That of GM‐CFC was 1·080 g/cm3.
Kinetics of Elimination of Antithrombin III Concentrate in Heparinized Patients
Authors: Marciniak E. , Gockerman J. P.
Published: July 2010

Summary.

The rate of elimination of injected antithrombin III (AT III) concentrate was investigated by measuring plasma AT III levels in two control subjects and four patients treated with continuous intravenous infusion of heparin. No significant differences were noted in the disappearance rate of injected AT III between controls and patients receiving heparin for several days. Their half‐time of AT III elimination was 8·4‐13·6 h. The patient in whom AT III concentrate was injected at the start of heparin therapy showed a very rapid decrease of AT III activity with a three‐fold increase in the elimination rate constant. Inactive, modified AT III protein present in purified AT III concentrate was found in the circulation of all injected patients. No evidence was obtained that this altered AT III was eliminated more rapidly than the unaltered AT III or that it was subjected to accelerated clearance during heparin therapy.
Factor VIII Clotting Antigen (VIIICAg) in Haemophilia Measured by Two Immunoradiometric Assays (IRMA) using Different Antibodies, and the Measurement of Inhibitors to Procoagulant Factor VIII (VIIIC) by IRMA
Authors: Furlong R. A. , Peake I. R. , Bloom A. L.
Published: July 2010

Summary.

Factor VIII clotting antigen (VIIICAg) was measured by immunoradiometric assay (IRMA) using two different antibodies. Both antibodies arose in polytransfused severe haemophiliacs and had similar titres against VIIIC. In 12 normal plasmas there was no significant difference in VIIICAg values obtained (VIIICAg (AbI) = VIIICAg (AbII)). In the majority of 15 severe haemophiliacs tested VIIICAg was undetectable by both antibodies. In 28 mild to moderate haemophiliacs VIIICAg (AbII) was significantly greater than VIIICAg (AbI) (P < 0·01) suggesting different antigenic determinants. The difference, however, was small and does not affect diagnosis of haemophilia. A modified IRMA has been used to measure and VIIIC inhibitors by competition of the inhibitor with 125I labelled VIIICAg antibodies for common antigenic determinants. Using an inhibitor of 225 Bethesda units as a standard, results by IRMA of inhibitors in severe haemophiliacs have been similar to those obtained by clotting assay, but with a sensitivity of 0·01 u/ml suggesting the possible use in the detection of weak inhibitors.
Benign monoclonal gammopathy and peripheral neuropathy
Authors: Ö Sby E. , Noring L. , Hast R. , Kjellin K. G. , Knutsson E. , Sidén Å
Published: July 2010

Summary.

Peripheral neuropathy has been described in malignant plasma cell dyscrasias such as multiple myeloma and Waldenström's macroglobulinaemia. Since it is not known whether the neuropathy is related to the plasma cell disorder or is a paramalignant phenomenon, 21 consecutive out‐patients with benign monoclonal gammopathy (BMG) were analysed for peripheral neuropathies. Eleven patients had noticed slight motor and/or sensory extremity symptoms. Clinical examination, electromyographic and electroneurographic studies of the upper and lower extremities were performed. In five patients all results indicated a neuropathy, six other patients had clinical signs of neuropathy and four additional patients had positive electromyographic and/or electroneurographic results. Thus, a total of 15 patients had clinical and/or electrophysiological results compatible with neuropathy. There were no significant differences in haematological parameters between the group where all results indicated a neuropathy and the totally negative group or between the two groups with and without clinical neuropathy. Thus, the benign form of plasma cell dyscrasias seems also to be associated with mild clinical or subclinical peripheral neuropathy.
Binding and inactivation of prostacyclin (PGI2) by human erythrocytes
Authors: Willems Charles , Stel Herbert V. , Aken Willem G. van , Mourik Jan A. van
Published: July 2010

Summary. Prostacyclin (PGI2), the most potent inhibitor of platelet aggregation known, is rapidly hydrolysed in aqueous solution at neutral pH to its inactive derivative 6‐keto‐PGF1α. In previous studies (Willems et al, 1979), we found that PGI2 is stabilized by plasma. Yet, PGI2 is rapidly inactivated in vivo. These findings prompted us to study the fate of PGI2 when incubated in whole human blood. After 20 min of incubation (at 37°C, pH 7·8), 29 ± 10% of the amount of PGI2, added to whole blood, remained in the supernatant plasma whereas, under the same conditions, 80 ± 3% and 86 ± 2% were recovered when PGI2 was added to platelet‐rich plasma or cell‐free plasma, respectively. When PGI2 was incubated with washed erythrocytes resuspended in plasma, 20 ± 15% of the added PGI2 remained in the supernatant after 10 min of incubation. These findings indicate that PGI2, when incubated with whole blood, is preferentially bound to erythrocytes. To study the kinetics of binding in more detail, [3H]PGI2 was incubated with washed erythrocytes resuspended in plasma. The binding was time‐ and concentration‐dependent. The observed binding of label represented binding of [3H]PGI2, because (1) acid‐treated label did not bind to erythrocytes; (2) no substantial binding of [3H]6‐keto‐PGF1α occurred, and (3) changes in the specific activity of the PGI2 preparation did not alter the binding percentage of labelled PGI2. The binding of [3H]PGI2 was not influenced by PGE1 or 6‐keto‐PGF1α. Repeated incubations of erythrocytes with PGI2 revealed that PGI2 was rapidly degraded into a biologically inactive non‐binding substance, presumably 6‐keto‐PGF1α. Binding and metabolism of PGI2 by erythrocytes may explain the apparent instability of PGI2 in whole blood and provides an explanation for the rapid loss of the biological effects of PGI2 on termination of the infusion.
125I fibrinogen turnover in polycythaemia: the effect of phlebotomy
Authors: Boughton B. J. , Dallinger K. J. C.
Published: July 2010

Summary. Patients with polycythaemia vera and secondary polycythaemia studied with 125I‐labelled fibrinogen, had a significantly increased plasma fibrinogen turnover. The abnormalities were greater in polycythaemia vera and correlated with platelet count but not with packed cell volume. In six patients with polycythaemia vera, phlebotomy reduced the packed cell volume to 0·46 or less. Although fibrinogen turnover decreased significantly in all patients, it remained outside the normal range in four cases. The concept of a prothrombotic state is discussed, and also the importance of these observations with respect to various forms of treatment.
RECOGNITION OF MARROW ELEMENTS BY NATURAL KILLER CELLS: ARE NK CELLS INVOLVED IN HAEMOPOIETC REGULATION?
Authors: O'Brien T. K. , Kendra J. A. , Stephens H. A. F. , Knight R. A. , Barrett A. J.
Published: July 2010

Summary. NK cells from young normal mice are cytolytic in vitro for a virus‐induced tumour cell line, YAC‐1. Cytotoxicity is inhibited by the addition of unlabelled homologous YAC‐1 cells and by regenerating bone marrow cells from the spleens of lethally irradiated, bone‐marrow‐grafted mice. Quiescent marrow from syngeneic and allogeneic mice produces little or no competition. This suggests that NK cells recognize, and may regulate, marrow progenitor cells.
β + Thalassaemia—Portuguese type: clinical, haematological and molecular studies of a newly defined form of β thalassaemia
Authors: Tamagnini G. P. , Lopes M. C. , Castanheira M. E. , Wainscoat J. S. , Wood W. G.
Published: July 2010

Summary. We have characterized 14 patients in 10 families with a mild form of homozygous β thalassaemia which has not been previously well defined. As these patients originate from a small area of northern Portugal we propose to call this β+ thalassaemia—Portuguese type. Clinically, the homozygotes range from asymptomatic to thalassaemia intermedia and they are characterized by low levels of HbF, <20%, indicating only a mild deficit in β globin production. Heterozygotes are indistinguishable from those with the more common types of β thalassaemia as regards red cell morphology, haemoglobin analysis and globin chain synthesis studies. Globin gene mapping excluded the presence of α thalassaemia in these patients and demonstrated no abnormalities in the βM‐like globin gene cluster. Restriction enzyme site polymorphisms around the β gene cluster are identical on both chromosomes in all of the homozygotes, confirming their homogeneity.
Platelet‐associated complement C3 in thrombocytopenic states
Authors: Kayser W. , Mueller‐Eckhardt C. , Bhakdi S. , Ebert Karola
Published: July 2010

Summary. Platelet‐associated complement components C3, C3d and C4 (PAC3, PAC3d, PAC4) were quantitated by a modification of the platelet radioactive anti‐IgG test using highly purified C3 antibodies in 74 patients with immune thrombocytopenia (ITP), 26 patients with presumed nonimmune thrombocytopenia (NTP), and 114 normal individuals.

Elevated PAC3 levels were found in 26 out of 74 patients with ITP (35%) and in 10 out of 26 patients with NTP. Although the percentage of elevated PAC3 values was higher in thrombocytopenic patients than in nonthrombocytopenic patients, no statistically significant correlation existed between platelet counts and PAC3 levels, neither for ITP nor for NTP. However, such a relationship was demonstrable between PAC3 and platelet‐associated IgG, both for ITP (P<0·05) as well as NTP patients (P<0·001).

We conclude that elevated PAC3 values are not restricted to immune thrombocytopenias. Quantitative differences of PAC3 between ITP and NTP patients suggest that part of the PAC3 is immunologically mediated and has a role in the pathogenesis of autoimmune thrombocytopenias.
Esterase cytochemistry in primary myelodysplastic syndromes and megaloblastic anaemias: demonstration of abnormal staining patterns associated with dysmyelopoiesis
Authors: Scott C. S. , Cahill A. , Bynoe A. G. , Ainley M. J. , Hough D. , Roberts B. E.
Published: July 2010

Summary. Acid alpha naphthyl acetate esterase (ANAE) and combined ANAE‐chloroacetate esterase cytochemistry was performed on 121 bone marrow aspirates from primary myelodysplastic syndromes (MDS) and a secondary dysplasia—megaloblastic anaemia (MA). The investigation demonstrated the presence of abnormal ANAE positive granulocyte populations in a significant proportion of cases. These cells, in which the staining patterns were characterized by atypical granular ANAE positivity and double ANAE‐chloroacetate reactions, were shown immunologically to lack the receptor and antigenic characteristics of monocytes and morphologically to be granulocytes. Isoelectric focusing, however, indicated that the atypical esterase cytochemistry of these granulocytes was due to the presence of markedly increased concentrations of ANAE isoenzymes usually found in monocytes. Atypical ANAE‐staining granulocytes were particularly evident in MDS marrows showing sideroblastic erythroid changes, whilst in MA they were mainly seen in cases of intermediate severity. It is suggested that these cells are associated with dysmyelopoietic changes in both malignant and non‐malignant conditions.
Immunoglobulin chain gene rearrangements in a t(4;ll) acute leukaemia with monocytoid blasts
Authors: Srivastava B. I. SAHAI , Wright John J. , Bakhshi Ajay
Published: July 2010

Summary. We report a case of acute leukaemia with the t(4;l 1) chromosomal translocation which, at initial diagnosis, had L‐l lymphoblasts that were positive for terminal deoxynucleotidyl transferase (TdT) and HLA‐DR but negative for myeloid cytochemical markers. At last relapse the patient had mostly monocytoid blasts which were now TdT negative but were positive for HLA‐DR, weakly positive for Sudan Black B (SB), periodic acid Schiffs (PAS), naphthol AS‐D acetate esterase (NSE), chloroacetate esterase (CAE) and negative for acid phosphatase (AP) and nitroblue tetrazolium (NBT) reduction. Treatment with 12‐o‐tetradecanoylphorbol‐13‐acetate (TPA) in vitro induced differentiation to macrophage‐Iike cells that were strongly positive for SB, PAS, NSE, AP, CAE and NBT reduction, indicating a latent monocyte‐like phenotype. Thus the leukaemic cell clone or a precurser clone with the t(4;l 1) translocation manifested a lymphoid phenotype at initial diagnosis and a monocytoid phenotype at relapse. Immunoglobulin gene analysis of the monocytoid relapse blasts revealed rearrangements of the heavy chain gene alleles and germline light chain genes. Thus, the leukaemia clone with the t(4;ll) chromosomal translocation could be a bipotential cell with heavy chain gene rearrangements occurring in a primitive cell which may retain the ability to differentiate along the myeloid‐monocytoid lineage in response to the appropriate stimulus. Alternatively, these characteristics may result from a transformation associated event.
Inhibition by interleukin‐1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias
Authors: Schooley John C. , Kullgren Birgitta , Allison Anthony C.
Published: July 2010

Summary.Highly purified and cloned preparations of interleukin‐1 (IL‐1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL‐1 and purified and cloned human IL‐1α and IL‐1β were approximately equipotent in this assay. IL‐1 inhibited the proliferation response of EPC even when added as long as 17h after Epo, suggesting that IL‐1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL‐1 on Epo‐induced proliferation, and PGE2had no demonstrable effect on the process. Tumornecrosis factor‐α and interferons β1, and γ did not affect Epoinduced proliferation. It is suggested that IL‐1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant‐cell arteritis, graft‐versus‐host disease and disorders associated with lymphocyte‐mediated suppression of erythropoiesis.
Histological and cytological heterogeneity of bone marrow in Philadelphia‐positive chronic myelogenous leukaemia at diagnosis
Authors: Lorand‐Metze Irene , Vassallo José , Souza Carmino A.
Published: July 2010

Summary. Cytological and histological features of the bone marrow in Philadelphia‐positive chronic myelogenous leukaemia (CML) at diagnosis were analysed in a prospective study. Formerly described (Frisch et al, 1984) subtypes GRAN and GRAN/MEG were found, and myelofibrosis and incipient blast crisis could also be detected. A more or less continuous spectrum of number and degree of atypias in megakaryocytes was found. Biopsy and imprint were complementary in making differential diagnosis of both subtypes. Cytologically, type GRAN/MEG was characterized by a mixed proliferation of neutrophil, eosinophil and basophil series, besides proliferation of megakaryocytes. Type GRAN showed a predominantly neutrophilic proliferation. The importance of performing bone marrow analysis in evaluation of CML patients is discussed.