bluuebunny/crossref_metadata_2025 huggingface dataset:
Third-order nonlinear optical properties of bismuth-borate glasses measured by conventional and thermally managed eclipse Z scan
Authors: Gomes A. S. L. , Falcão Filho E. L. , de Araújo Cid B. , Rativa Diego , de Araujo R. E. , Sakaguchi Koichi , Mezzapesa Francesco P. , Carvalho Isabel C. S. , Kazansky Peter G.
Published: February 2007

Third-order nonlinearity one order of magnitude larger than silica is measured in bismuth-borate glasses presenting a fast response (<200fs). The results for the sign and magnitude of the nonlinearity were obtained using a combination of the eclipse Z scan with thermal nonlinearity managed Z scan, whereas the Kerr shutter technique was employed to obtain the electronic time response of the nonlinearity, all performed with 76MHz repetition rate 150fs pulses at 800nm. Conventional Z scans in the picosecond regime at 532 and 1064nm were also independently performed, yielding the values of the third-order nonlinear susceptibilities at those wavelengths. The results obtained for the femtosecond response, enhanced third-order nonlinearity of this glass (with respect to silica), place this glass system as an important tool in the development of photonics devices. Electro-optical modulators, optical switches, and frequency converters are some of the applications using second-order nonlinear properties of the Bi-glass based on the rectification model.
Vanadium-based Ohmic contacts to n-AlGaN in the entire alloy composition
Authors: France Ryan , Xu Tao , Chen Papo , Chandrasekaran R. , Moustakas T. D.
Published: February 2007

The authors report on the formation and evaluation of V-based Ohmic contacts to n-AlGaN films in the entire alloy composition. The films were produced by plasma assisted molecular beam epitaxy and doped n-type with Si. The conductivity of the films was determined to vary from 103to10−2(Ωcm)−1 as the AlN mole fraction increases from 0% to 100%. Ohmic contacts were formed by e-beam evaporation of V(15nm)∕Al(80nm)∕V(20nm)∕Au(100nm). These contacts were rapid thermal annealed in N2 for 30s at various temperatures. The optimum annealing temperature for this contact scheme to n-GaN is about 650°C and increases monotonically to about 1000°C for 95%–100% AlN mole fraction. The specific contact resistivity was found to be about 10−6Ωcm2 for all films up to 70% AlN mole fraction and then increases to 0.1–1Ωcm2 for films from 95%–100% AlN mole fraction. These results were accounted for by hypothesizing that vanadium, upon annealing, interacts with the nitride film and forms vanadium nitride, which is consistent with reports that it is a metal with low work function.
Strain distribution of thin InN epilayers grown on (0001) GaN templates by molecular beam epitaxy
Authors: Delimitis A. , Komninou Ph. , Dimitrakopulos G. P. , Kehagias Th. , Kioseoglou J. , Karakostas Th. , Nouet G.
Published: February 2007

A structural characterization of thin InN films is performed to determine the post-growth strain distribution, using electron microscopy techniques. A 60° misfit dislocation network at the InN∕GaN interface effectively accommodates the lattice mismatch. The InN in-plane lattice parameter, which remained practically constant throughout the epilayer thickness, was precisely determined by electron diffraction analysis, and cross-section and plan-view lattice images. Image analysis using the geometric phase and projection methods revealed a uniform distribution of the residual tensile strain along the growth and lateral directions. The in-plane strain is primarily attributed to InN island coalescence during the initial stages of growth.
Large flexible nanowire grid visible polarizer made by nanoimprint lithography
Authors: Chen Lei , Wang Jian Jim , Walters Frank , Deng Xuegong , Buonanno Mike , Tai Stephen , Liu Xiaoming
Published: February 2007

117 and 150nm pitch polymer gratings were successfully fabricated on plastic substrate over large area by nanoimprint lithography. Nanowire-grid polarizers were made by depositing Al on the sidewalls of the gratings at oblique angles. The effects of grating period, grating linewidth, Al depth, and thickness were studied in detail. Excellent contrast (∼1000:1) and high transmittance (80%–90%) (without antireflection coating) at the wavelength of 500nm and above were demonstrated.
Generation of electricity in GaN nanorods induced by piezoelectric effect
Authors: Su W. S. , Chen Y. F. , Hsiao C. L. , Tu L. W.
Published: February 2007

Conversion of mechanical energy into electric energy has been demonstrated in GaN nanorods. The measurement was achieved by deflecting GaN nanorods with a conductive atomic force microscope PtIr tip in contact. The mechanism relies on the coupling between piezoelectric and semiconducting properties in GaN nanorod, which creates a strain field and drives the charge flow across the nanorod. The result shown here opens up an opportunity for harvesting electricity from wasted mechanical energies in the ambient environment, which may lead to the realization of self-powered nanodevices.
Increasing NADH oxidation reduces overflow metabolism in
Saccharomyces cerevisiae
Authors: Vemuri G. N. , Eiteman M. A. , McEwen J. E. , Olsson L. , Nielsen J.
Published: February 2007

Respiratory metabolism plays an important role in energy production in the form of ATP in all aerobically growing cells. However, a limitation in respiratory capacity results in overflow metabolism, leading to the formation of byproducts, a phenomenon known as “overflow metabolism” or “the Crabtree effect.” The yeast
Saccharomyces cerevisiae
has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely respiratory to mixed respiratory and fermentative. It is well known that glucose repression of respiratory pathways occurs at high glycolytic fluxes, resulting in a decrease in respiratory capacity. Despite many years of detailed studies on this subject, it is not known whether the onset of the Crabtree effect is due to limited respiratory capacity or is caused by glucose-mediated repression of respiration. When respiration in
S. cerevisiae
was increased by introducing a heterologous alternative oxidase, we observed reduced aerobic ethanol formation. In contrast, increasing nonrespiratory NADH oxidation by overexpression of a water-forming NADH oxidase reduced aerobic glycerol formation. The metabolic response to elevated alternative oxidase occurred predominantly in the mitochondria, whereas NADH oxidase affected genes that catalyze cytosolic reactions. Moreover, NADH oxidase restored the deficiency of cytosolic NADH dehydrogenases in
S. cerevisiae
. These results indicate that NADH oxidase localizes in the cytosol, whereas alternative oxidase is directed to the mitochondria.
Diazonamide toxins reveal an unexpected function for ornithine δ-amino transferase in mitotic cell division
Authors: Wang Gelin , Shang Libin , Burgett Anthony W. G. , Harran Patrick G. , Wang Xiaodong
Published: February 2007

We have studied a naturally occurring small-molecule antimitotic called diazonamide A. Diazonamide A is highly effective at blocking spindle assembly in mammalian cell culture and does so through a unique mechanism. A biotinylated form of diazonamide A affinity purifies ornithine δ-amino transferase (OAT), a mitochondrial enzyme, from HeLa cell and
Xenopus
egg extracts. In the latter system, the interaction between diazonamide A and OAT is regulated by RanGTP. We find that specific OAT knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death, the effects largely phenocopying diazonamide A treatment in these cell lines. Our experiments reveal an unanticipated, paradoxical role for OAT in mitotic cell division and identify the protein as a target for chemotherapeutic drug development.
O-Specific polysaccharide conjugate vaccine-induced IgG antibodies prevent invasion of
Shigella
into Caco-2 cells and may be curative
Authors: Chowers Yehuda , Kirschner Joachim , Keller Nathan , Barshack Iris , Bar-Meir Simon , Ashkenazi Shai , Schneerson Rachel , Robbins John , Passwell Justen H.
Published: February 2007

The
O
-specific polysaccharide (O-SP) domain of
Shigella
LPS is both an essential virulence factor and a protective antigen for this genus. A critical level of serum IgG anti-O-SP was shown to confer immunity to shigellosis, likely by complement-mediated bacteriolysis of the inoculum. Conjugate
Shigella
O-SP vaccines were shown to be safe and immunogenic in children, and, in a preliminary study,
Shigella sonnei
vaccine was protective in young adults. Characteristic of shigellosis is bacterial invasion of intestinal cells. Incubation of shigellae with postimmunization but not preimmunization sera of children vaccinated with
S. sonnei
or
Shigella flexneri
2a O-SP conjugate vaccines inhibited in a type-specific and dose-dependent manner
in vitro
invasion of intestinal epithelial cells (Caco-2) and the infection-associated increases in IL-1β and IL-8 mRNA and extracellular cytokine levels. Pretreatment of these sera or of Caco-2 cells with O-SP abrogated these effects also in a type-specific and dose-dependent manner. Confocal microscopy demonstrated antibody-specific inhibition of bacterial adhesion to HeLa cells. These protective effects were duplicated by IgG purified from these sera. These results suggest a dual role for IgG anti-O-SP. In addition to lysis of the inoculum in immune individuals, the newly synthesized IgG anti-O-SP in patients may terminate an established infection by inhibiting shigellae released from epithelial cells from invading new ones. A critical level of IgG anti-O-SP could, therefore, have a protective as well as a curative role in shigellosis.
Internal strain regulates the nucleotide binding site of the kinesin leading head
Authors: Hyeon Changbong , Onuchic José N.
Published: February 2007

In the presence of ATP, kinesin proceeds along the protofilament of microtubule by alternated binding of two motor domains on the tubulin binding sites. Because the processivity of kinesin is much higher than other motor proteins, it has been speculated that there exists a mechanism for allosteric regulation between the two monomers. Recent experiments suggest that ATP binding to the leading head (L) domain in kinesin is regulated by the rearward strain built on the neck-linker. We test this hypothesis by explicitly modeling a C
α
-based kinesin structure whose motor domains are bound on the tubulin binding sites. The equilibrium structures of kinesin on the microtubule show disordered and ordered neck-linker configurations for the L and trailing head, respectively. The comparison of the structures between the two heads shows that several native contacts present at the nucleotide binding site in the L are less intact than those in the binding site of the rear head. The network of native contacts obtained from this comparison provides the internal tension propagation pathway, which leads to the disruption of the nucleotide binding site in the L. Also, using an argument based on polymer theory, we estimate the internal tension built on the neck-linker to be
f
≈ 12–15 pN. Both of these conclusions support the experimental hypothesis.
Kinetic models of redox-coupled proton pumping
Authors: Kim Young C. , Wikström Mårten , Hummer Gerhard
Published: February 2007

Cytochrome
c
oxidase, the terminal enzyme of the respiratory chain, pumps protons across the inner mitochondrial membrane against an opposing electrochemical gradient by reducing oxygen to water. To explore the fundamental mechanisms of such redox-coupled proton pumps, we develop kinetic models at the single-molecule level consistent with basic physical principles. We demonstrate that pumping against potentials >150 mV can be achieved purely through electrostatic couplings, given an asymmetric arrangement of charge centers; however, nonlinear gates are essential for highly efficient real enzymes. The fundamental requirements for proton pumping identified here highlight a possible evolutionary origin of cytochrome
c
oxidase pumping. The general design principles are relevant also for other molecular machines and suggest future applications in biology-inspired fuel cells.
Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry
Authors: Molina Henrik , Horn David M. , Tang Ning , Mathivanan Suresh , Pandey Akhilesh
Published: February 2007

Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total of 1,435 phosphorylation sites from human embryonic kidney 293T cells, of which 1,141 (≈80%) were not previously described. A detailed comparison of ETD and collision-induced dissociation (CID) modes showed that ETD identified 60% more phosphopeptides than CID, with an average of 40% more fragment ions that facilitated localization of phosphorylation sites. Although our data indicate that ETD is superior to CID for phosphorylation analysis, the two methods can be effectively combined in alternating ETD and CID modes for a more comprehensive analysis. Combining ETD and CID, from this single study, we were able to identify 80% of the known phosphorylation sites in >1,000 phosphorylated peptides analyzed. A hierarchical clustering of the identified phosphorylation sites allowed us to discover 15 phosphorylation motifs that have not been reported previously. Overall, ETD is an excellent method for localization of phosphorylation sites and should be an integral component of any strategy for comprehensive phosphorylation analysis.
Acupuncture Regulates Leukocyte Subpopulations in Human Peripheral Blood
Authors: Yamaguchi Nobuo , Takahashi Takashi , Sakuma Masahiro , Sugita Toshiroh , Uchikawa Kumiko , Sakaihara Satoshi , Kanda Tsugiyasu , Arai Matsuo , Kawakita Kenji
Published: February 2007

Acupuncture has recently been attracting more and more people throughout the world as an alternative treatment, however little is known about its physiological activities (i.e. immune system). We examined acupuncture both quantitatively and qualitatively by measuring CD‐positive cell counts and cytokine expression levels in the blood, to determine the activity of T cells, B cells, macrophages and natural killer (NK) cells. Fifteen milliliters of peripheral blood obtained from 17 healthy volunteers aged 21–51 years, were analyzed using flow cytometry before and after acupuncture treatment. There was a statistically significant increase in the number of CD2+, CD4+, CD8+, CD11b+, CD16+, CD19+, CD56+ cells as well as IL‐4, IL‐1β and IFN‐γ levels in the cells after acupuncture stimulation of meridian points. These observations indicate that acupuncture may regulate the immune system and promote the activities of humoral and cellular immunity as well as NK cell activity. In this article, we discussed how acupuncture regulated leukocyte numbers and functions since they are considered to be potential indicators for evaluating complementary and alternative medicine.
Dual priming oligonucleotide system for the multiplex detection of respiratory viruses and SNP genotyping of CYP2C19 gene
Authors: Chun Jong-Yoon , Kim Kyoung-Joong , Hwang In-Taek , Kim Yun-Jee , Lee Dae-Hoon , Lee In-Kyoung , Kim Jong-Kee
Published: February 2007

Successful PCR starts with proper priming between an oligonucleotide primer and the template DNA. However, the inevitable risk of mismatched priming cannot be avoided in the currently used primer system, even though considerable time and effort are devoted to primer design and optimization of reaction conditions. Here, we report a novel dual priming oligonucleotide (DPO) which contains two separate priming regions joined by a polydeoxyinosine linker. The linker assumes a bubble-like structure which itself is not involved in priming, but rather delineates the boundary between the two parts of the primer. This structure results in two primer segments with distinct annealing properties: a longer 5′-segment that initiates stable priming, and a short 3′-segment that determines target-specific extension. This DPO-based system is a fundamental tool for blocking extension of non-specifically primed templates, and thereby generates consistently high PCR specificity even under less than optimal PCR conditions. The strength and utility of the DPO system are demonstrated here using multiplex PCR and SNP genotyping PCR.
Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish
Authors: Rai Kunal , Chidester Stephanie , Zavala Chad V. , Manos Elizabeth J. , James Smitha R. , Karpf Adam R. , Jones David A. , Cairns Bradley R.
Published: February 2007

The roles of DNA methyltransferase-2 (DNMT2) enzymes are controversial; whether DNMT2 functions primarily as a nuclear DNA methyltransferase or as a cytoplasmic tRNA methyltransferase, and whether DNMT2 activity impacts development, as dnmt2 mutant mice or Drosophila lack phenotypes. Here we show that morpholino knockdown of Dnmt2 protein in zebrafish embryos confers differentiation defects in particular organs, including the retina, liver, and brain. Importantly, proper organ differentiation required Dnmt2 activity in the cytoplasm, not in the nucleus. Furthermore, zebrafish Dnmt2 methylates an RNA species of ∼80 bases, consistent with tRNA methylation. Thus, Dnmt2 promotes zebrafish development, likely through cytoplasmic RNA methylation.
UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans
Authors: Von Stetina Stephen E. , Fox Rebecca M. , Watkins Kathie L. , Starich Todd A. , Shaw Jocelyn E. , Miller David M.
Published: February 2007

In Caenorhabditis elegans, VA and VB motor neurons arise as lineal sisters but synapse with different interneurons to regulate locomotion. VA-specific inputs are defined by the UNC-4 homeoprotein and its transcriptional corepressor, UNC-37/Groucho, which function in the VAs to block the creation of chemical synapses and gap junctions with interneurons normally reserved for VBs. To reveal downstream genes that control this choice, we have employed a cell-specific microarray strategy that has now identified unc-4-regulated transcripts. One of these genes, ceh-12, a member of the HB9 family of homeoproteins, is normally restricted to VBs. We show that expression of CEH-12/HB9 in VA motor neurons in unc-4 mutants imposes VB-type inputs. Thus, this work reveals a developmental switch in which motor neuron input is defined by differential expression of transcription factors that select alternative presynaptic partners. The conservation of UNC-4, HB9, and Groucho expression in the vertebrate motor circuit argues that similar mechanisms may regulate synaptic specificity in the spinal cord.
Improved quality of root fillings provided by general dental practitioners educated in nickel–titanium rotary instrumentation
Authors: Molander A. , Caplan D. , Bergenholtz G. , Reit C.
Published: February 2007

Aim  To test the hypothesis that an increased utilization of nickel–titanium rotary instrumentation (NTRI) by general dental practitioners will lead to an increased frequency of good quality root fillings. A second aim was to determine whether the educational format would exert influence on the quality.

Methodology  Dentists were assigned at random to three intervention groups: a 4‐h lecture (L‐group, n = 40); a 4‐h lecture plus a full day hands‐on course (LH‐group, n = 40); or a control group receiving no instruction (n = 68). The control group received education later on in the study. Radiographs of two root filled molar teeth per dentist were selected at random before the start of the education program and after a 6‐month clinical learning period. Using length, seal and shape of root‐fillings a 5‐level variable was created.

Results  The rate of good quality root fillings increased after the introduction of NTRI. Calculated over all types of roots the frequency of excellent (score 1) root fillings increased from 31% to 51% (P = 0.006) in the L‐group and from 27% to 47% (P = 0.016) in the LH‐group. The frequency of low quality root‐fillings (score 5) dropped in the L‐group from 22% to 16% (P = 0.29) and in the LH‐group from 13% to 9% (P = 0.48). No statistically significant difference was seen among the controls.

Conclusions  When NTRI technology replaced manual stainless steel techniques the rate of good quality root fillings increased. A significant drop in the rate of low quality root fillings was not found.
Papulonecrotic tuberculid‐like eruptions after Bacille Calmette‐Guerin vaccination
Authors: TAKADA Tomoaki , YAMASHITA Toshiharu , SATO Makito , KAWAKAMI Yoshiaki , TOMINAGA Akihiro , ONO Ichiro , JIMBOW Mihoko , TSUTSUMI Hiroyuki , JIMBOW Kowichi
Published: February 2007

One of the specific skin lesions occurring after Bacille Calmette‐Guerin (BCG) vaccination is generalized tuberculid‐like eruptions, which occur rarely, but have a tendency to heal spontaneously. Their pathogenesis and relationship to “true” tuberculids are poorly understood. This report presents a case of a 6‐month‐old girl who developed generalized papulonecrotic tuberculid‐like eruptions after BCG vaccination. The skin lesions healed spontaneously in 3 months. Culture of blood, gastric juice and reverse transcription polymerase chain reaction (RT‐PCR) of papulonecrotic skin biopsies were all negative for Mycobacterium tuberculosis. Histopathology of papulonecrotic eruptions revealed marked epidermal necrosis, perivascular lymphocytic infiltrates and epidermotropic infiltration of lymphocytes showing markers of CD3+ lymphocytes (90–95% of all infiltrating cells), CD4+ (40–50%), CD8+ (40–50%), and CD45RO+ (70%). In contrast, the BCG vaccination site revealed intradermal granuloma with epithelioid cells, occasional giant cells and infiltration of lymphocytes consisting of CD3+ (60–70%), CD4+ (40–50%), CD8+ (30–40%), CD45RO+ (40%), CD79a+ (30–40%), and CD20+ (20–30%). Our patient did not reveal any signs indicative of tuberculosis. Papulonecrotic lesions were therefore called papulonecrotic tuberculid‐like eruptions, rather than tuberculids, that occurred after BCG vaccination and appeared to derive from a hypersensitive reaction mediated by immune lymphocytic infiltration.
Twenty nail dystrophy in vitiligo
Authors: KHANDPUR Sujay , BANSAL Arika , SHARMA Vinod K , BHATTI Sahibinder Singh , SINGH Manoj K
Published: February 2007

Twenty nail dystrophy (TND) is a manifestation of several dermatoses and its association with vitiligo is rare. It may be consequent upon a common autoimmune insult to the melanocytes and the nail matrix. We report a patient of acrofacial vitiligo who developed TND. Nail matrix biopsy revealed focal lichenoid reaction and chronic inflammatory infiltrate in the dermal papillae and around blood vessels. Hematological, biochemical and serological investigations showed no evidence of other autoimmune diseases.
Case of sequentially occurring lesions of facial lichen sclerosus following the lines of Blaschko
Authors: KIM Young Jin , LEE Eun‐So
Published: February 2007

Extragenital lichen sclerosus (LS) is usually asymptomatic and appears as ivory‐ or porcelain‐white macules, papules and plaques. It is most common on the neck, shoulders and upper portion of the trunk. To date, the linear form of extragenital LS corresponding to the lines of Blaschko on the trunk or limbs has been rarely reported. We describe a 25‐year‐old Korean woman with sequentially occurring lesions of extragenital LS confined to the face following the lines of Blaschko.
Treatment setting and baseline substance use severity interact to predict patients' outcomes
Authors: Tiet Quyen Q. , Ilgen Mark A. , Byrnes Hilary F. , Harris Alex H. S. , Finney John W.
Published: February 2007

Aims  This study tested the hypothesis that patients with more severe substance use disorders (SUDs) at intake respond better when treated in more structured and intensive settings (i.e. in‐patient/residential versus out‐patient), whereas patients with less severe SUD problems have similar outcomes regardless of treatment setting.

Design, setting and participants  Up to 50 new patients were selected randomly from each of a random and representative sample of 50 Department of Veterans Affairs (VA) SUD treatment programs (total n = 1917 patients), and were followed‐up an average of 6.7 months later (n = 1277).

Measures  Patients completed a brief self‐report version of the Addiction Severity Index (ASI) at baseline and at follow‐up.

Findings  In mixed‐model regression analyses, baseline substance use severity predicted follow‐up substance use severity and there were no main effects of treatment setting. However, interaction effects were found, such that more severe patients experienced better alcohol and drug outcomes following in‐patient/residential treatment versus out‐patient treatment; on the other hand, patients with lower baseline ASI drug severity had better drug outcomes following out‐patient treatment than in‐patient treatment. Treatment setting was unrelated to alcohol outcomes in patients with less severe ASI alcohol scores.

Conclusions  Results provide some support to the matching hypothesis that for patients who have higher levels of substance use severity at intake, treatment in in‐patient/residential treatment settings is associated with better outcomes than out‐patient treatment. More research needs to be conducted before in‐patient/residential settings are further reduced as a part of the SUD continuum of care in the United States.
The JAK2 V617F mutation involves B‐ and T‐lymphocyte lineages in a subgroup of patients with Philadelphia‐chromosome negative chronic myeloproliferative disorders
Authors: Larsen Thomas Stauffer , Christensen Jacob Haaber , Hasselbalch Hans Carl , Pallisgaard Niels
Published: February 2007

The JAK2 V617F mutation is a frequent genetic event in the three classical Philadelphia‐chromosome negative chronic myeloproliferative disorders (Phneg.‐CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Its occurrence varies in frequency in regards to phenotype. The mutation is found in the majority of patients with PV and about half of the patients with ET and IMF. These diseases are clonal stem cell disorders arising in an early stem cell progenitor. The level in the stem cell hierarchy on which the initiating genetic events and the JAK2 V617F mutation occurs is not known. The mutation has so far been detected in all cells of the myeloid lineage, whereas the potential clonal involvement of the lymphoid lineage is controversial. In this study, we detected the JAK2 V617F mutation by real‐time quantitative PCR (qPCR) in both B‐lymphocytes and T‐lymphocytes in a subgroup of patients with Phneg.‐CMPDs. These results demonstrate the origin of the JAK2 V617F positive disorders in an early stem cell with both lymphoid and myeloid differentiation potential.
Higher thrombin concentrations are required to induce platelet apoptosis than to induce platelet activation
Authors: Leytin V. , Allen D. J. , Lyubimov E. , Freedman J.
Published: February 2007

Primarily known as an inducer of blood coagulation and platelet activation, thrombin also triggers platelet apoptosis. This study demonstrated that the platelet activation response is much more sensitive than platelet apoptosis to thrombin treatment. Thrombin concentrations of 0·5–1 nmol/l activated almost all platelets, but only a small fraction underwent apoptosis, suggesting that at these relatively low thrombin concentrations, platelets may perform haemostasis but not be involved in programmed cell death. At high thrombin concentrations of 10–100 nmol/l, generated during blood coagulation, 30–40% of platelets became apoptotic, indicating that hypercoagulable states may be associated with increased numbers of apoptotic platelets.
The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients
Authors: SZCZEPANIK A. B. , SIKORSKA A. , SLOMKOWSKI M. , KONOPKA L.
Published: February 2007

Administration of vinca alkaloids (VA) to chronic corticosteroid refractory immune thrombocytopenia (ITP) patients results in a temporary increase of platelet count. The aim of the study was to evaluate the efficacy of vinca alkaloids in preparing adult corticosteroid refractory chronic ITP patients for splenectomy as well as to compare the costs of this method with costs of applying intravenous immunoglobulins. The study included 12 chronic ITP patients refractory to corticosteroids applied for 3–144 months. The patients were prepared for splenectomy with average 3.0 (from 1 to 4) 2‐h intravenous infusions of vinca alkaloids at 7 day intervals. In eight patients, vincristin was used in a total dose of 6 mg (2 mg per infusion), in two patients, vinblastin was used in total dose of 30 mg (10 mg per infusion), and in two patients, vincristin and vinblastin infusions were administered alternatively. In nine of the 12 treated patients (75%) the platelet count increased to ≥80 × 109/l, which allowed safe splenectomy. Three patients unreactive to VA treatment were prepared for splenectomy with intravenous gammaglobulin infusions. Splenectomy was performed in 12 patients, in eight with laparoscopic method, in four with classic method. No complications during surgical intervention were observed. In none of the VA treated patients was myelosupression or liver or/and kidney dysfunction observed. Splenectomy resulted in normalization of platelet count in all patients after operation and in six of nine patients followed up for 10 months (on the average). Matching of VA costs with treatment efficacy and comparison with similar costs for intravenous immunoglobulin treatment revealed many fold lower costs of the former method.
Association of the interleukin‐2 receptor alpha (IL‐2Rα)/CD25 gene region with Graves’ disease using a multilocus test and tag SNPs
Authors: Brand Oliver J. , Lowe Christopher E. , Heward Joanne M. , Franklyn Jayne A. , Cooper Jason D. , Todd John A. , Gough Stephen C. L.
Published: February 2007

Objective  A small number of immune response genes have been consistently associated with the common autoimmune conditions. Recently, a linkage disequilibrium (LD) mapping approach, using tag single nucleotide polymorphisms (SNPs), identified genetic association between type 1 diabetes (T1D) and the interleukin‐2 receptor alpha (IL‐2Rα)/CD25 gene region on chromosome 10p15. Because certain autoimmune diseases, such as autoimmune thyroid disease (AITD) and T1D cluster together in certain families, we sought to determine if the TID‐associated CD25 region was also associated with Graves’ disease (GD).

Design  We performed a case‐control association study of 20 tag SNPs.

Patients  1896 GD patients were collected from seven major centres in the UK and 1822 geographically matched controls from the 1958 British Birth Cohort.

Measurements  The 20 tag SNPs were analysed using a multilocus test to identify an association between GD and the CD25 region. Odds ratios (ORs) were calculated for the tag SNPs, allowing a comparison with previous results for T1D.

Results  The multilocus test provided statistical evidence of an association between GD and the CD25 region (P = 4·5 × 10−4), with the pattern of association of the 20 tag SNPs similar to that found in T1D.

Conclusions  Association with GD, as well as that previously reported with T1D, suggests that the CD25 region is acting as a general susceptibility locus for autoimmune disease, and is consistent with a major role for the IL‐2‐receptor pathway in the development and function of T cells in the control of autoimmunity.
Impairment of bone mass development in children with chronic cholestatic liver disease
Authors: De Albuquerque Taveira Adriana Távora , Fernandes Maria Inez Machado , Galvão Lívia Carvalho , Sawamura Regina , De Mello Vieira Enaldo , De Paula Francisco José Albuquerque
Published: February 2007

Objective  To analyse aspects of mineral metabolism, bone mineral density (BMD), bone remodelling activity and serum IGF‐1 levels in children with chronic cholestatic disease (CCLD).

Patients and measurements  A total of 13 children with chronic cholestatic liver disease (CCLD; mean age 7·2 ± 4·8 years) and 22 control subjects (mean age 7·6 ± 4·5 years) were studied. Serum osteocalcin, bone alkaline phosphatase (BAP), 25‐hydroxyvitamin D, PTH and IGF‐1 levels and urinary deoxypyridinoline were determined. BMD was measured by dual‐energy X‐ray absorptiometry in the lumbar spine, total hip and whole body. Lumbar spine areal BMD was converted mathematically to apparent volumetric BMD (aBMD) and corrected for the bone age of the patient.

Results  Z‐score of lumbar spine BMD was lower in CCLD patients than in controls and the difference was maintained when BMD was expressed as aBMD (control = 0·107 ± 0·02 vs. CCLD = 0·092 ± 0·02 g/cm3, P < 0·05) and after conversion for bone age. All participants showed normal 25‐hydroxyvitamin D levels, with no significant differences in serum levels of 25‐hydroxyvitamin D and PTH between groups. IGF‐1 levels were significantly lower in the CCLD group (control = 19·6 ± 16·8 vs. CCLD = 6·4 ± 7·6 nmol/l, P < 0·05) and a positive correlation was observed between whole body BMD and IGF‐1 in this group.

Conclusions  These results indicate that CCLD limits bone mass gain in children. A reduction in hepatic IGF‐1 production might be responsible, at least in part, for the low bone mass of these patients.
A formative analysis of how preservice teachers learn to use technology
Authors: Kay R.
Published: February 2007

Abstract A comprehensive, formal comparison of strategies used by preservice teachers to learn how to use new technology has yet to be researched. Understanding the relative strengths and weakness of learning strategies would provide useful guidance to educators and students. The purpose of the current study was to explore the effectiveness of four learning strategies: collaboration, using authentic tasks, formal instruction and exploratory learning. Seventy‐four preservice teachers (25 male, 49 female) were surveyed at the beginning and end of an 8‐month, consecutive, Bachelor of Education programme, with respect to their learning strategies, change in computer knowledge and use of computers in the classroom. Collaborative learning and use of authentic tasks were the most preferred strategies – formal instruction was the least preferred. A collaborative approach to learning was the best predictor of gains in computer knowledge. Authentic tasks and collaborative strategies were significant predictors of teacher use of computers in the classroom. Preference for authentic tasks was the only predictor of student use of computers. Regardless of strategy preference, selecting more than one primary learning tool was significantly correlated with amount learned and use of the computers in the classroom. Ability was not related to strategy preference. Finally, females preferred collaborative approach to learning, although they were significantly more open to using multiple strategies than males.
Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce
Authors: Canonica G. W. , Baena‐Cagnani C. E. , Bousquet J. , Bousquet P. J. , Lockey R. F. , Malling H.‐J. , Passalacqua G. , Potter P. , Valovirta E.
Published: February 2007

Specific Immunotherapy for respiratory allergy is used since about one century and there is now solid documentation of its efficacy. Nevertheless, the methods and experimental designs used in clinical trials are quite heterogeneous and there is no unanimously accepted methodological standard. Many studies are planned with study designs that may not confirm the clinical value of SIT as an effective treatment to reduce disease severity. To ensure that patients are treated based on sound scientific evidence and to minimize the risk of misusing limited financial resources for scientific studies, the World Allergy Organization (WAO) convened a group of experts to provide guidelines for the methodology of future immunotherapy studies.

This document summarizes the recommendations for study design, patients’ selection, appropriate outcomes and statistical treatment to be used in planning and performing clinical trials with specific immunotherapy.
Global Alliance against Chronic Respiratory Diseases
Authors: Bousquet J. , Dahl R. , Khaltaev N.
Published: February 2007

Hundreds of millions of people of all ages suffer from chronic respiratory diseases which include asthma and respiratory allergies, chronic obstructive pulmonary disease, occupational lung diseases and pulmonary hypertension. More than 500 million patients live in developing countries or in deprived populations. Chronic respiratory diseases are increasing in prevalence. Although the cost of in action is clear and unacceptable, chronic respiratory diseases and their risk factors receive in sufficient attention from the health care community, government officials, media, patients and families. The Fifty‐Third World Health Assembly recognized the enormous human suffering caused by chronic diseases and requested the World Health Organization (WHO) Director General to give priority to the prevention and control of chronic diseases, with special emphasis on developing countries. This led to the formation of the WHO Global Alliance against Chronic Respiratory Diseases (GARD). GARD is a voluntary alliance of organizations, institutions and agencies working towards a common vision to improve global lung health according to local needs. GARD is developed in a stepwise approach using the following three planning steps: estimate population need and advocate action; formulate and adopt policy; and identify policy implementation steps.
Access to inhaled corticosteroids is key to improving quality of care for asthma in developing countries
Authors: Ait‐Khaled N. , Enarson D. A. , Bissell K. , Billo N. E.
Published: February 2007

Asthma is a worldwide public health problem affecting about 300 million people. The majority of persons living with asthma are in the developing world where there is limited access to essential drugs. The financial burden for persons living with asthma and their families, as well as for healthcare systems and governments, is very high. Inadequate treatment and the high cost of medications leads to disability, absenteeism and poverty. Despite the existence of effective asthma medications and international guidelines, and progress made in the implementation of such guidelines over the last decade, the high cost of essential asthma medications remains a major obstacle for patient access to treatment in developing countries. The International Union Against Tuberculosis and Lung Disease has evaluated this problem and created an Asthma Drug Facility (ADF) so that countries can purchase affordable, good quality essential drugs for asthma. The ADF uses pooled procurement along with other purchasing and supply strategies to obtain the lowest possible prices. Accompanied by the implementation of standardized asthma management, the increased affordability of drugs provided by the ADF should bring rapid and significant health and cost benefits for patients, their communities and governments.
Allergic disorders in African countries: linking immunology to accurate phenotype
Authors: Van Ree R. , Yazdanbakhsh M.
Published: February 2007

Identification and characterization of risk and protective factors for allergy is important for developing strategies for prevention or treatment. The prevalence of allergy is clearly higher in affluent countries than in developing countries like, e.g. Africa. Especially in urban areas of developing countries, allergy is however on the increase. In Africa, we have the unique opportunity to investigate risk and protective factors and the influence of urbanization and westernization, i.e. almost to take a look at Europe, Australia or the USA as they were before their allergy epidemics. Moreover, migrants from developing to affluent countries experiencing an increased burden of allergy provide new insights into risk and protective factors. Allergen exposure, diet and infections are the major exogenous influences playing a role as risk and protective factors. Depending on the nature, timing, chronicity and level of exposure, each of them can promote or inhibit allergy. Perhaps with the exception of infections, availability of data from Africa on their role in the development of allergy is limited. Detailed epidemiological studies in rural and urban Africa combined with basic immunological research are needed to unravel mechanisms of increase in allergy and of protection. The maturation of the immune system at young age under influence of exogenous factors results in differences in T‐cell‐skewing (Th1/Th2/Treg) and humoral responses. It is essential to perform studies from a ‘non‐Eurocentric’ angle (e.g. local allergens, locally validated questionnaires and diagnostic procedures). Such studies will provide the affluent countries with new leads to combat the allergy epidemic and more importantly help prevent it in Africa.
Prevalence of symptoms of childhood asthma, allergic rhinoconjunctivitis and eczema in the Pacific: The International Study of Asthma and Allergies in Childhood (ISAAC)
Authors: Foliaki S. , Annesi‐Maesano I. , Daniel R. , Fakakovikaetau T. , Magatongia M. , Tuuau‐Potoi N. , Waqatakirewa L. , Cheng S.K. , Pearce N.
Published: February 2007

The International Study of Asthma and Allergies in Childhood (ISAAC) has provided valuable information regarding international prevalence patterns and potential risk factors for asthma, allergic rhinoconjunctivitis and eczema. However, the only Pacific countries that participated in ISAAC Phase I were Australia and New Zealand, and these included only a small number of Pacific children. Phase III has involved not only repeating the Phase I survey to examine time trends, but also to include centres and countries which are of interest but did not participate in Phase I. The ISAAC Phase III study was therefore conducted in the Pacific (in French Polynesia, New Caledonia, Tonga, Fiji Islands, Samoa, Cook Islands, Tokelau Islands and Niue). The overall prevalence rates of current symptoms (in the last 12 months) were 9.9% for asthma, 16.4% for allergic rhinoconjunctivitis and 10.7% for atopic eczema. The prevalence of current wheezing (9.9%) was generally much lower than that has been observed in Pacific children in New Zealand (31%), but there was considerable variation between the various Pacific centres: Tokelau Islands (19.7%), Tonga (16.2%), Niue (12.7%), French Polynesia (11.3%), Cook Islands (10.6%), Fiji Islands (10.4%), New Caledonia (8.2%) and Samoa (5.8%). The reasons for these differences in prevalence across the Pacific are unclear and require further research. The finding that prevalence levels are generally considerably lower than those in Pacific children in New Zealand adds to previous evidence that children who migrate experience an altered risk of asthma as a result of exposure to a new environment during childhood.
Colo‐colic intussusception associated with Henoch–Schönlein purpura in adults
Authors: Goda Fuminori , Maeba Takashi , Usuki Hisashi , Karasawa Yukihiko , Izuishi Kunihiko , Ishimura Ken , Senda Shoichi , Maeta Hajime
Published: February 2007

Henoch–Schönlein purpura (HSP) is often seen in childhood and is a self‐limiting illness, and complication with intussusception is rare in adults. The case is reported of a 74‐year‐old man who was diagnosed with intussusception with HSP by ultrasonography on day of admission. Conservative therapy was started. However, his abdominal symptoms worsened, so he underwent laparotomy 3 days after admission. Histological study of the resected specimens demonstrated necrosis in the intussuscepted colon induced by HSP vasculitis. Bowel necrosis with intussusception in adult HSP is rare and might easily be overlooked. Thus special attention should be paid to gastrointestinal manifestations and, in an abdominal emergency, timely surgical intervention is life‐saving.
Long‐term outcome of chronic hepatitis B based on histological grade and stage
Authors: Park Byung Kyu , Park Young Nyun , Ahn Sang Hoon , Lee Kwan Sik , Chon Chae Yoon , Moon Young Myoung , Park Chanil , Han Kwang‐Hyub
Published: February 2007

Background and Aim:  This study evaluated the long‐term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage.

Methods:  A total of 188 patients with chronic hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re‐evaluated based on histological grade and stage.

Results:  During follow‐up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto‐periportal activity. The development of cirrhosis correlated well with the grade of porto‐periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared‐up without normalization than in patients whose ALT levels flared‐up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow‐up were independent prognostic factors for chronic hepatitis B.

Conclusions:  The results demonstrate that histological grade and stage, and biochemical profile during follow‐up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long‐term outcome of chronic hepatitis B patients.
Carbamazepine poisoning managed with haemodialysis and haemoperfusion in three adolescents
Authors: BEK KENAN , KOÇAK ŞULE , ÖZKAYA OZAN , YILMAZ YUNUS , AYDIN ÖMER FARUK , TAŞDÖVEN ÇǦDEM SAǦ
Published: February 2007

Carbamazepine is a widely used antiepileptic agent. Accidental or suicidal overdose in children is not uncommon. Acute toxicity is associated with seizures, coma, arrhythmias and death in severe cases. Here we report three adolescents with carbamzepine overdose, two managed with standard low‐flux haemodialysis and one with charcoal haemoperfusion. Our report emphasizes that haemodialysis might be a cheaper and easier alternative for carbamazepine overdose in milder cases, with fewer side‐effects than haemoperfusion.