bluuebunny/crossref_metadata_2025 huggingface dataset:
High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis
Authors: Nash Richard A. , Bowen James D. , McSweeney Peter A. , Pavletic Steven Z. , Maravilla Kenneth R. , Park Man-soo , Storek Jan , Sullivan Keith M. , Al-Omaishi Jinan , Corboy John R. , DiPersio John , Georges George E. , Gooley Theodore A. , Holmberg Leona A. , LeMaistre C. Fred , Ryan Kate , Openshaw Harry , Sunderhaus Julie , Storb Rainer , Zunt Joseph , Kraft George H.
Published: May 2003

There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (≥ 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy. (Blood. 2003;102:2364-2372)
Proliferation kinetics of subpopulations of human marrow cells determined by quantifying in vivo incorporation of [2H2]-glucose into DNA of S-phase cells
Authors: Schwartz Gretchen N. , Vance Barbara A. , Levine Benjamin M. , Fukazawa Motoharu , Telford William G. , Cesar Denise , Hellerstein Marc , Gress Ronald E.
Published: May 2003

This report investigated in vivo turnover kinetics of marrow hematopoietic progenitors and precursors using a recently developed stable isotope–mass spectrometric technique (SIMST). Human subjects were administered a 2-day infusion of 6,6-[2H2]-glucose, a nontoxic stable isotope-labeled form of glucose, which becomes incorporated into DNA of all S-phase cells. The percent [2H2]-glucose incorporated into DNA in the form of [2H2]-deoxyadenosine (%[2H2]-dA enrichment) was determined by gas chromatography–mass spectrometry. The rate constant of replacement of unlabeled by labeled DNA strands (labeling kinetics) was used to calculate population turnover kinetics of CD34+ cells, CD133+ cells, and CD133–CD34+ cells. The observed mean replacement half-life (t1/2) was 2.6 days for CD34+ cells, 2.5 days for CD133–CD34+ cells, and 6.2 days for CD133+ cells. Results from the estimated rate constant of replacement of labeled by unlabeled DNA (delabeling kinetics) also demonstrated slower turnover rates for CD133+ cells than for CD133–CD34+ cells. Although there was a relatively rapid initial decrease in the %[2H2]-dA enrichment, low levels of labeled DNA persisted in CD34+ cells for at least 4 weeks. The results indicate the presence of subpopulations of CD34+ cells with relatively rapid turnover rates and subpopulations with a slower t1/2 of 28 days. Results also demonstrate that in vivo [2H2]-glucose-SIMST is sensitive enough to detect differences in turnover kinetics between erythroid and megakaryocyte lineage cells. These studies are the first to demonstrate the use of in vivo [2H2]-glucose-SIMST to measure in vivo turnover kinetics of subpopulations of CD34+ cells and precursors in healthy human subjects.
Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion
Authors: Powell Jerry S. , Ragni Margaret V. , White Gilbert C. , Lusher Jeanne M. , Hillman-Wiseman Carol , Moon Tom E. , Cole Veronica , Ramanathan-Girish Sandhya , Roehl Holger , Sajjadi Nancy , Jolly Douglas J. , Hurst Deborah
Published: May 2003

In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain–deleted human factor VIII (hFVIII) gene. Infusions were well tolerated. Tests for replication competent retrovirus have been negative. Polymerase chain reaction (PCR) analyses demonstrate the persistence of vector gene sequences in peripheral blood mononuclear cells in 3 of 3 subjects tested. Factor VIII was measured in serial samples using both a one-stage clotting assay and a chromogenic assay. While no subject had sustained FVIII increases, 9 subjects had FVIII higher than 1% on at least 2 occasions 5 or more days after infusion of exogenous FVIII, with isolated levels that ranged from 2.3% to 19%. Pharmacokinetic parameters of exogenous FVIII infused into subjects 13 weeks after vector infusion showed an increased half-life (T1/2; P < .02) and area under the curve (AUC, P < .04) compared with prestudy values. Bleeding frequency decreased in 5 subjects compared with historical rates. These results demonstrate that this retroviral vector (hFVIII(V)) is safe and, in some subjects, persists more than a year in peripheral blood mononuclear cells, with measurable factor VIII levels and with increased available FVIII activity (increased T1/2 and AUC) after infusion of exogenous FVIII concentrate.
CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells
Authors: Deaglio Silvia , Capobianco Andrea , Bergui Luciana , Dürig Jan , Morabito Fortunato , Dührsen Ulrich , Malavasi Fabio
Published: May 2003

The prognosis for patients with B-cell chronic lymphocytic leukemia (B-CLL) is generally less favorable for those expressing CD38. Our working hypothesis is that CD38 is not merely a marker in B-CLL, but that it plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling. Other cellular models indicated that molecular density and surface organization are critical for CD38 functionality. Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. On reaching a specific expression threshold, CD38 becomes an efficient receptor in purified B-CLL cells. Indeed, mAb ligation is followed by Ca2+ fluxes and by a markedly increased proliferation. The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell–receptor (BCR) complex and CD19. On mAb binding, CD38 translocates to the membrane lipid microdomains, as shown by a colocalization with the GM1 ganglioside and with CD81, a raft-resident protein. Finally, CD38 signaling in IL-2–treated B-CLL cells prolonged survival and induced the appearance of plasmablasts, providing a pathogenetic hypothesis for the occurrence of Richter syndrome.
Oligomerization of RANTES is required for CCR1-mediated arrest but not CCR5-mediated transmigration of leukocytes on inflamed endothelium
Authors: Baltus Thomas , Weber Kim S. C. , Johnson Zoë , Proudfoot Amanda E. I. , Weber Christian
Published: May 2003

Chemokines control inflammatory leukocyte recruitment. The propensity of chemokines such as CC chemokine ligand 5 (CCL5)/RANTES (regulated on activation, normal T cell expressed and secreted) to bind to glycosaminoglycans and to form higher order oligomers has been shown to be essential for its in vivo activity. However, the specific functional relevance of RANTES oligomerization for distinct steps of leukocyte recruitment on inflamed endothelium mediated by the RANTES receptors CC chemokine receptor 1 (CCR1) and CCR5 remains undefined. We studied RANTES mutants with deficient oligomerization in an assay in which recruitment of monocytes and CD45RO+ CD4+ T cells is triggered by RANTES immobilized on activated endothelium under flow conditions. Notably, the formation of higher order RANTES oligomers was crucial for CCR1-mediated arrest but not for CCR5-mediated spreading/transmigration in flow or transendothelial chemotaxis of leukocytes. Efficient leukocyte arrest in flow but not transmigration may thus require the presentation of RANTES oligomers to bridge surface-bound RANTES and CCR1.
PSGL-1 participates in E-selectin–mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and α4 integrin
Authors: Katayama Yoshio , Hidalgo Andrés , Furie Barbara C. , Vestweber Dietmar , Furie Bruce , Frenette Paul S.
Published: May 2003

The nature and exact function of selectin ligands involved in hematopoietic progenitor cell (HPC) homing to the bone marrow (BM) are unclear. Using murine progenitor homing assays in lethally irradiated recipients, we found that the P-selectin glycoprotein ligand-1 (PSGL-1) plays a partial role in HPC homing to the BM (a reduction of about 35% when the P-selectin binding region is blocked). Blockade of both PSGL-1 and α4 integrin did not further enhance the effect of anti-α4 integrin (a reduction of about 55%). We suspected that E-selectin ligands might contribute to the remaining homing activity. To test this hypothesis, HPC homing assays were carried out in E-selectin–deficient recipients and revealed a profound alteration in HPC homing when E-selectin and α4 integrin were inactivated (> 90% reduction). Competitive assays to test homing of long-term repopulating stem cells revealed a drastic reduction (> 99%) of the homed stem cell activity when both α4 integrin and E-selectin functions were absent. Further homing studies with PSGL-1–deficient HPCs pretreated with anti-α4 integrin antibody revealed that PSGL-1 contributes to approximately 60% of E-selectin ligand–mediated homing activity. Our results thus underscore a major difference between mature myeloid cells and immature stem/progenitor cells in that E-selectin ligands cooperate with α4 integrin rather than P-selectin ligands.
A Constitutively Active Somatic Mutation of the Human Lutropin Receptor Found in Leydig Cell Tumors Activates the Same Families of G Proteins as Germ Line Mutations Associated with Leydig Cell Hyperplasia
Authors: Hirakawa Takashi , Ascoli Mario
Published: May 2003

Using a Leydig tumor cell line (MA-10) transiently transfected with the human lutropin receptor (hLHR) and mutants thereof, we examined the identity of the G proteins activated by the agonist-engaged hLHR-wild type (wt) and by three of its naturally occurring constitutively active mutants. Two of the mutants examined, L457R in transmembrane helix 3 and D578Y in transmembrane helix 6, are germ-line mutations found in boys with Leydig cell hyperplasia and precocious puberty. The third, D578H, is a somatic mutation found in Leydig cell tumors in boys with precocious puberty. We show that the hLHR-wt and the three mutants activate the Gs, Gi/o, and Gq/11, but not the G12/13, families of G proteins. The activation of these G proteins by the hLHR-wt occurs only when engaged by agonist, but their activation by the L457R, D578Y, and D578H mutants occurs independently of agonist stimulation. We conclude that the G proteins activated by constitutively active mutants of the hLHR associated with Leydig cell hyperplasia or tumors are identical and are the same as those activated by the agonist-engaged hLHR-wt. If there was preferential activation of some G protein families by the somatic D578H mutation found in Leydig cell tumors as opposed to the germ line mutations found in Leydig cell hyperplasia, then one could envision mechanisms by which the D578H mutant would be oncogenic. The data presented here suggest that such mechanisms do not need to be considered.
Pre- and Postnatal Propylthiouracil-Induced Hypothyroidism Impairs Synaptic Transmission and Plasticity in Area CA1 of the Neonatal Rat Hippocampus
Authors: Sui Li , Gilbert M. E.
Published: May 2003

Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.
Differential Control of Adrenal and Sympathetic Catecholamine Release by α2-Adrenoceptor Subtypes
Authors: Brede Marc , Nagy Gábor , Philipp Melanie , Sørensen Jakob B. , Lohse Martin J. , Hein Lutz
Published: May 2003

In the adrenergic system, release of the neurotransmitter norepinephrine from sympathetic nerves is regulated by presynaptic inhibitory α2-adrenoceptors, but it is unknown whether release of epinephrine from the adrenal gland is controlled by a similar short feedback loop. Using gene-targeted mice we demonstrate that two distinct subtypes of α2-adrenoceptors control release of catecholamines from sympathetic nerves (α2A) and from the adrenal medulla (α2C). In isolated mouse chromaffin cells, α2-receptor activation inhibited the electrically stimulated increase in cell capacitance (a correlate of exocytosis), voltage-activated Ca2+ current, as well as secretion of epinephrine and norepinephrine. The inhibitory effects of α2-agonists on cell capacitance, voltage-activated Ca2+ currents, and on catecholamine secretion were completely abolished in chromaffin cells isolated from α2C-receptor-deficient mice. In vivo, deletion of sympathetic or adrenal feedback control led to increased plasma and urine norepinephrine (α2A-knockout) and epinephrine levels (α2C-knockout), respectively. Loss of feedback inhibition was compensated by increased tyrosine hydroxylase activity, as detected by elevated tissue dihydroxyphenylalanine levels. Thus, receptor subtype diversity in the adrenergic system has emerged to selectively control sympathetic and adrenal catecholamine secretion via distinct α2-adrenoceptor subtypes. Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation.
Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis
Authors: Lee Jibak , Iwai Toshiharu , Yokota Takehiro , Yamashita Masakane
Published: May 2003

Sister chromatid cohesion is maintained from DNA replication to metaphase-to-anaphase transition by multisubunit protein complexes called cohesin, which include at least four proteins, SMC1α, SMC3, Rad21 and either SA1 or SA2, in mammalian somatic cells. We report here the first evidence of the involvement of Rec8 protein, a mammalian homolog of yeast Rec8p, in meiosis-specific chromosome behavior in mammals. In immunoblotting and immunohistochemical analysis using specific antibodies against mouse Rec8,we found that Rec8 was expressed in the testis but not in the kidney or liver;more precisely, it was expressed in spermatocytes and spermatids but not in spermatogonia or other somatic cells. We also found that Rec8 is present in both phosphorylated and dephosphorylated states in vivo. Immunoprecipitation analyses revealed that Rec8 associates with other cohesin proteins, SMC1β(meiosis-specific protein) and SMC3 and with a component of synaptonemal complexes, SCP3, but not with SMC1α. In meiotic chromosome spreads, Rec8 was localized along the axial/lateral elements of the synaptonemal complexes in meiotic prophase from the leptotene to diplotene stages. At later stages,diakinesis and metaphase I, Rec8 was localized along the interstitial axes of chromosomes, including both centromere and arm regions of chromosomes. However, concomitantly with separation of homologous chromosomes in anaphase I, Rec8 was no longer detected along the arm regions, while it persisted on centromere regions up to metaphase II. In anaphase II, the centromeric signals were diminished. We propose from these results that mammalian Rec8 protein, in association with SMC3 and SMC1β but not SMC1α, is involved in meiosis-specific chromosome behavior, and that homologous chromosome separation is triggered by selective loss of Rec8 from chromosome arms in meiosis I, while sister chromatid cohesion is maintained until metaphase II/anaphase II transition by centromeric Rec8 during mammalian meiosis.
Associative learning and memory inLymnaea stagnalis: how well do they remember?
Authors: Lukowiak Ken , Sangha Susan , McComb Chloe , Varshney Nishi , Rosenegger David , Sadamoto Hisayo , Scheibenstock Andi
Published: May 2003

The search for `the how and the where' of memory formation in the brain,the engram, is still one of the unattained `Holy Grails' of neuroscience. Over the years, various paths have been trodden in attempts to attain this goal,and while tantalizing glimpses appear now and then on the scientific horizon,the Grail still has not been grasped. One of the paths that investigators have walked is the invertebrate `model system' approach. Some invertebrates possess relatively simple nervous systems that mediate relatively simple behaviours that are both interesting and trainable. In this commentary, we would like to shed light on a relatively new player, the pond snail Lymnaea stagnalis L., that is being used in the quest to illuminate `the how and the where' the nervous systems encode and store memory. We will show that it is possible to demonstrate that a single neuron is a site of memory formation and storage for a form of associative learning in this lowly snail. It may be that the Grail is a little closer to being grasped.
The effects of gape angle and bite point on bite force in bats
Authors: Dumont Elizabeth R. , Herrel Anthony
Published: May 2003

Models of mammalian mastication predict that bite force is affected by both the degree of mouth opening (gape angle) and the point along the tooth row at which force is transferred to a food item (bite point). Despite the widespread use of these models in comparative analyses, experimental data documenting bite force in non-human mammals are extremely limited. The goal of this study is to document variation in non-stimulated bite force associated with change in gape angle and bite point in a broad range of species. We focus on plant-visiting bats because they exhibit a relatively primitive cranial morphology and are good models for generalized mammals. Assessments of the relationship between gape angle and bite force within and among species demonstrate that bite force decreases significantly as gape angle increases. The relationship between bite force and bite point within each of seven species demonstrates that unilateral molar biting universally generates the highest forces while the unilateral canine biting produces the lowest forces. Bilateral canine biting is intermediate. Beyond these general patterns,differences among species suggest that bite force reflects variation in craniofacial architecture. Finally, these data suggest that behavioral variation in gape angle and bite point may be important variables in comparative, functional analyses of feeding.
The influence of wing–wake interactions on the production of aerodynamic forces in flapping flight
Authors: Birch James M. , Dickinson Michael H.
Published: May 2003

We used two-dimensional digital particle image velocimetry (DPIV) to visualize flow patterns around the flapping wing of a dynamically scaled robot for a series of reciprocating strokes starting from rest. The base of the wing was equipped with strain gauges so that the pattern of fluid motion could be directly compared with the time history of force production. The results show that the development and shedding of vortices throughout each stroke are highly stereotyped and influence force generation in subsequent strokes. When a wing starts from rest, it generates a transient force as the leading edge vortex (LEV) grows. This early peak, previously attributed to added-mass acceleration, is not amenable to quasi-steady models but corresponds well to calculations based on the time derivative of the first moment of vorticity within a sectional slice of fluid. Forces decay to a stable level as the LEV reaches a constant size and remains attached throughout most of the stroke. The LEV grows as the wing supinates prior to stroke reversal, accompanied by an increase in total force. At stroke reversal, both the LEV and a rotational starting vortex (RSV) are shed into the wake, forming a counter-rotating pair that directs a jet of fluid towards the underside of the wing at the start of the next stroke. We isolated the aerodynamic influence of the wake by subtracting forces and flow fields generated in the first stroke, when the wake is just developing, from those produced during the fourth stroke, when the pattern of both the forces and wake dynamics has reached a limit cycle. This technique identified two effects of the wake on force production by the wing: an early augmentation followed by a small attenuation. The later decrease in force is consistent with the influence of a decreased aerodynamic angle of attack on translational forces caused by downwash within the wake and is well explained by a quasi-steady model. The early effect of the wake is not well approximated by a quasi-steady model, even when the magnitude and orientation of the instantaneous velocity field are taken into account. Thus,the wake capture force represents a truly unsteady phenomenon dependent on temporal changes in the distribution and magnitude of vorticity during stroke reversal.
The tremble dance of honey bees can be caused by hive-external foraging experience
Authors: Thom Corinna
Published: May 2003

The tremble dance of honey bee nectar foragers is part of the communication system that regulates a colony's foraging efficiency. A forager that returns to the hive with nectar, but then experiences a long unloading delay because she has difficulty finding a nectar receiver bee, will perform a tremble dance to recruit additional nectar receiver bees. A forager that experiences a short unloading delay will perform a waggle dance to recruit more nectar foragers. A long unloading delay was until now the only known cause of tremble dancing. However, several studies suggested that factors at the food source may also cause tremble dancing. Here I test whether one of these factors, crowding of nectar foragers at the food source, stimulates tremble dancing because it causes long unloading delays. To do so, I increased the density of nectar foragers at a food source by suddenly reducing the size of an artificial feeder, and recorded the unloading delay experienced by each forager, as well as the dance she performed, if any. A forager's unloading delay was measured as the time interval between entering the hive and either (1) the first unloading contact with a nectar receiver bee, or (2) the start of the first dance, if dancing began before the first unloading contact. I also recorded the unloading delays and dances of nectar foragers that returned from natural food sources. The results show that crowding of nectar foragers at the food source increases the probability of tremble dancing, but does not cause long unloading delays, and that tremble dancers that foraged at natural food sources also often have short unloading delays. When the cause of the tremble dance is not a low supply of nectar receiver bees, the tremble dance may have a function in addition to the recruitment of nectar receiver bees.
Repeated bouts of high-intensity exercise and muscle glycogen sparing in the rat
Authors: Raja Ghazala , Bräu Lambert , Palmer T. Norman , Fournier Paul A.
Published: May 2003

Even in the absence of food intake, several animal species recovering from physical activity of high intensity can replenish completely their muscle glycogen stores. In some species of mammals, such as in rats and humans,glycogen repletion is only partial, thus suggesting that a few consecutive bouts of high-intensity exercise might eventually lead to the sustained depletion of their muscle glycogen. In order to test this prediction, groups of rats with a lead weight of 10% body mass attached to their tails were subjected to either one, two or three bouts of high-intensity swimming, each bout being separated from the next by a 1 h re covery period. Although glycogen repletion after the first bout of exercise was only partial, all the glycogen mobilised in subsequent bouts was completely replenished during the corresponding recovery periods and irrespective of muscle fibre compositions. The impact of repeated bouts of high-intensity exercise on plasma levels of fatty acids, acetoacetate and β-hydroxybutyrate suggests that the metabolic state of the rat prior to the second and third bouts of exercise was different from that before the first bout. In conclusion, rats resemble other vertebrate species in that without food intake there are conditions under which they can replenish completely their muscle glycogen stores from endogenous carbon sources when recovering from high-intensity exercise. It remains to be established, however, whether this capacity is typical of mammals in general.
Permeation and toxicity of ethylene glycol and methanol in larvae of Anopheles gambiae
Authors: Liu Xiang-Hong , Pan Hongjun , Mazur Peter
Published: May 2003

In this study, we applied proton NMR to measure the permeation of two cryoprotective agents (CPAs), ethylene glycol (EG) and methanol, into 1st instar Anopheles larvae. Calibration with standard solutions of EG or methanol (0–10 mol l-1) confirmed the reliability of the NMR measurements for determining the concentration of these solutes. To assess permeation, larvae were immersed in 1.5 mol l-1 EG or 1.5 mol l-1 methanol for different periods of time at 22°C. The concentration of both CPAs in the larvae was then measured as a function of exposure time using 1H-NMR spectroscopy. Results show that after a 6 h exposure to 1.5 mol l-1 EG, the larval concentration of EG reaches a maximum value of 1.44 mol l-1, which is 96% of the theoretical maximum. By contrast, after just 1 h exposure to 1.5 mol l-1 methanol, the larval methanol concentration reaches its maximum, which, however, is only 75% of the theoretical maximum. Toxicity data show that larval survival remains 91% and 95% after 4 h and 1 h exposure to 1.5 mol l-1 EG and 1.5 mol l-1 methanol, respectively,at which time the larval concentration of EG and methanol has risen to 1.21 mol l -1 and 1.13 mol l-1, respectively. These results suggest that CPAs such as EG and methanol do permeate Anopheleslarvae to up to 81% and 75% of equilibrium, respectively, before the exposure becomes toxic.
Regulation of branchial Na+/K+-ATPase in common carpCyprinus carpioL. acclimated to different temperatures
Authors: Metz Juriaan R. , van den Burg Erwin H. , Bonga Sjoerd E. Wendelaar , Flik Gert
Published: May 2003

Isogenic carp Cyprinus carpio L. were acclimated to water temperatures of 15, 22 and 29°C for at least 8 weeks. The acclimations consistently resulted in slightly, but significantly, different plasma osmolality, sodium, potassium and chloride concentrations between the groups studied. Plasma total and ionic calcium levels were unaffected, indicating successful adaptation. The apparent changes in set point for plasma ion levels are explained by altered sodium pump activity and hormonal control of branchial permeability to water and ions. It appears that in 15°C-acclimated fish, a lower apparent Na+/K+-ATPase activity is compensated by strongly enhanced Na+/K+-ATPase expression (determined biochemically and immunohistochemically). In 29°C-acclimated fish, the higher ambient temperature activates the enzyme. Arrhenius plots for branchial Na+/K+-ATPase preparations of the three groups of fish suggest the occurrence of different enzyme isoforms or protein (in)stability as explanations for differences in apparent enzyme activities, rather than temperature-dependent changes in membrane fluidity. As for hormonal control over permeability, prolactin mRNA expression (and anticipated production and release) is lower in fish kept at 29°C, suggesting that control over branchial permeability to water and ions needs to be downregulated at higher temperatures. In so doing, enhanced sodium pump activity is balanced by a controlled passive ion loss to fine-tune plasma sodium levels. Basal plasma cortisol levels did not correlate positively with Na+/K+-ATPase expression, but doubling plasma cortisol levels in control fish by administering exogenous cortisol (for 7 days, using implanted minipumps and thus stress-free) enhanced Na+/K+-ATPase expression. This effect must be the result of a glucocorticoid action of the steroid: in fish, mineralocorticoid receptors have higher affinity for cortisol than glucocorticoid receptors. At a lower ambient temperature, branchial Na+/K+-ATPase expression is upregulated to counteract the temperature-inhibited activity of the sodium pump, perhaps via a mineralocorticoid receptor.
Nitronyl Nitroxide Substituted Aniline o-APNN with a Three-dimensional Hydrogen Bond Network Showing Ferromagnetic Interaction
Authors: Doi Kentaro , Ishida Takayuki , Nogami Takashi
Published: May 2003

o-Aminophenyl nitronyl nitroxide (o-APNN) was prepared as the first aniline-substituted nitronyl nitroxide. X-Ray crystallographic analysis reveals a 3-D hydrogen bonded network due to the branching nature of –NH2. Magnetic measurements indicate the presence of ferromagnetic interaction.
The newest epidemic: a review of HIV/AIDS in Central and Eastern Europe
Authors: Kelly Jeffrey A , Amirkhanian Yuri A
Published: May 2003

HIV/AIDS has emerged as a grave public health threat in Central and Eastern Europe and in the Central Asian republics over the past five years. Massive political, social, cultural, and behavioural changes - along with economic upheaval and collapse of the public health infrastructure in many countries - have created circumstances conducive to the rapid spread of HIV. This paper reviews HIV and sexually transmitted disease (STD) data for all countries in the region, as well as behavioural, social, cultural, and other HIV epidemic enabling factors. The epidemiological picture of HIV in the region is mixed. Russia, Ukraine, Moldova and Belarus already have advanced epidemics. Some other countries in the region share similar enabling factors and have seen a very high proportion of their total number of HIV infections detected in only the past 18 months, indicating the emergence of recent epidemics. Several countries are more stable in their HIV incidence. Behavioural studies indicate that risky sexual and injection related practices are common in many vulnerable populations. HIV prevention steps, if taken quickly enough and on a large scale, can limit the scope of the HIV epidemic that is now unfolding in Central and Eastern Europe. This will require new models of government/non-governmental organization cooperation, policy approaches for addressing structural factors underlying the epidemic, and attention to human rights protection.
Molecular epidemiology of endemic ciprofloxacin-resistant Neisseria gonorrhoeae in Liverpool
Authors: Corkill J E , Komolafe A J , Neal T J , Mortimore A , Alawattegama A B , Hart C A
Published: May 2003

Ciprofloxacin-resistant Neisseria gonorrhoeae had been rarely detected on Merseyside and when found was associated with β-lactamase producing strains, imported from abroad. However, in August 2000, two cases of infection with ciprofloxacin-resistant β-lactamase-negative strains occurred in sexually unrelated patients with no history of foreign travel. Over the next 18 months a total of 120 patients presented with ciprofloxacin-resistant gonococci, from which 99 patient strains were available for study. Gonococcal DNA was subjected to molecular fingerprinting by polymerase chain reaction amplification followed by Taq1 digestion of their opa genes. Twelve differing opa-types were found, but 79 patients were infected with a single genotype, opa-type 1. The sexual histories of the majority of this group indicated acquisition in Merseyside. This endemic strain was further characterized by having the same amino acid substitutions on gyrA and parC genes. An endemic clone of ciprofloxacin-resistant N. gonorrhoeae has been established on Merseyside necessitating the introduction of ceftriaxone as first-line treatment. Despite the presence of 11 other clones in the city, opa type-1 strains have not yet been displaced, raising the possibility that this strain is endowed with added virulence/endemicity traits or that a number of source patients have not yet been found.
Sensitivity of microscopy for the rapid diagnosis of gonorrhoea in men and women and the role of gonorrhoea serovars
Authors: Manavi Kaveh , Young Hugh , Clutterbuck Dan
Published: May 2003

Auditing the sensitivity of microscopic diagnosis of gonorrhoea is recommended by the current guidelines.

A retrospective study was performed of 596 cases of positive cultures for Neisseria gonorrhoeae in modified New York City culture (MNYC) media diagnosed from 1995 to 1999. The sensitivity of the cervical slides in women was 51% while in men who have sex with men (MSM) the sensitivity of urethral and rectal slides were 89% and 54% respectively. The sensitivity of urethral slides in heterosexual men was 84%. Neisseria serovar 1B02 among MSM and serovar 1B31 among women were mostly undiagnosed with microscopy. Serovars 1A05, 1A21, B08 among heterosexual men were exclusively associated with negative microscopy.

Microscopy is important in the rapid detection and treatment of gonorrhoea. Infections with certain serovars are less likely to be detected by microscopy; making them more likely to spread within the community. Culture from different ano-genital sites is essential to maximize detection of gonorrhoea in all patients.
Oral manifestations of HIV–AIDS in Nigerian patients
Authors: Anteyi Kate O , Thacher Tom D , Yohanna Stephen , Idoko John I
Published: May 2003

Because of the unique features of the AIDS epidemic in West Africa, we sought to determine if the spectrum of oral lesions among Nigerian patients with HIV-AIDS differs from that found in other regions. Of 500 patients examined, 266 (53%) had oral lesions. Lesions due to candidiasis were present in 244 (49%), while other oral lesions were infrequent (<3% for each of the other types). Oral lesions were associated with advanced disease stage ( P < 0.001), a history of urethritis in men ( P < 0.001), and alcohol ( P < 0.001) and tobacco use ( P = 0.03). A significantly lower prevalence of oral lesions (6%) was found among the 32 patients receiving antiretroviral drug treatment.
Prevalence, disclosure and interpretations of sexual activities in a sample of Canadian college-aged blood donors
Authors: Mair M , Barrett S P , Campbell T , Ditto B
Published: May 2003

This study assessed the prevalence, level of disclosure, and interpretations of sexual activities in a sample of 123 college-aged blood donors in Montreal, Quebec. Within six months of their donation, participants completed an anonymous questionnaire designed to assess sexual definitions, levels of disclosure to sexual partners, as well as prevalence of various blood safety behavioural risks. Responses indicated that (1) there was a lack of consensus regarding what constitutes 'sex', (2) levels of sexual disclosure varied widely, and (3) participants engaged in numerous blood safety behavioural risk activities. These results are discussed with respect to their implications for how people think about sex, particularly in the blood donation context. Suggestions to improve specific blood donor screening questions are also presented.
‘Levelling the playing field, activating the players’: New Labour and ‘the cycle of disadvantage’
Authors: Deacon Alan
Published: May 2003

English

New Labour’s ‘third way’ on welfare has been much debated. It is argued here that there is substance to the claim that third way thinking integrates elements of hitherto conflicting perspectives.This is illustrated by New Labour’s interpretation of new evidence on the extent of intergenerational continuities in disadvantage. New Labour’s understanding of the cycle of disadvantage draws on five conflicting explanations of such continuities.The commitment to end child poverty was due in part to the impact of this evidence, and New Labour’s eclectic approach has led it to revisit issues neglected for much of the post-war period.
Education as industrial policy: New Labour’s marriage of the social and the economic
Authors: Stedward Gail
Published: May 2003

English

Education has been repositioned in the Labour policy hierarchy – no longer a straightforward social policy item, it now straddles the social and economic agendas to an extent that makes it possible to talk about education as industrial policy.This article begins by charting the trajectory of ideas and trends which coalesced in the marriage of economic and social policy, the prioritising of education and its role as a key component in the New Labour analysis of Britain’s renewal. It then looks at the role of education in New Labour’s ‘new industrial policy’ and examines some of the problems arising from its approach.
Process research in healthcare: towards three-dimensional learning
Authors: Langley Ann , Denis Jean-Louis , Lamothe Lise
Published: May 2003

English

This article argues that process research provides a way of adding depth and perspective to our understanding of organisational change in healthcare and in other fields. We present a three-dimensional model of the research process and argue for the importance of all three dimensions in building useful process knowledge that will have relevance beyond specific settings. We use the model to illustrate our own research process, providing examples of our work on the implementation of hospital mergers. We conclude by discussing some of the dilemmas we have faced and continue to face in conducting this type of research.
Process evaluation of health promotion interventions
Authors: Parry-Langdon Nina , Bloor Michael , Audrey Suzanne , Holliday Joanne
Published: May 2003

English

This article uses two extended illustrations of current process evaluations to address areas of difficulty in health promotion design. There are no clear solutions to methodological problems that are rooted in competition between paradigms. Further,any design adopted must adapt to constraints of resources and time. Nevertheless, a multi-method approach can provide a pragmatic and realistic way forward, with the precise mix of methods selected being adapted to the particular requirements and constraints of the intervention project being evaluated.
Where next for policy evaluation? Insights from researching National Health Service modernisation
Authors: Bate Paul , Robert Glenn
Published: May 2003

This article takes a critical and reflective look at the summative evaluation approach often employed in the context of NHS policy making and puts the case for an evaluation method which is based on a particular concept or variant of formative evaluation. The article uses two contemporary case study evaluations (one summative and one formative) to illustrate the key questions and issues, dilemmas and tensions associated with conducting evaluations within the visible and highly charged political context of the NHS. It concludes that what is at stake here is not only a question of methodology but a redefinition of the relationship between researchers and policy makers and practitioners.
Modification of leather properties by grafting. I. Effect of monomer chain on the physico‐mechanical properties of grafted leather
Authors: Abd El‐Ghaffar M. A. , El‐Sayed N. H. , Masoud R. A.
Published: May 2003

Although leather has a number of desirable properties such as thermal stability and fire retardancey, in addition to high toughness, it has a few drawbacks such as weight, high water absorption, poor soil and rot resistance, and nonuniformity. If these defects are overcome, leather's usefulness would be further enhanced and its competitive position with respect to synthetics would increase. This study reports the physical and mechanical properties of buffalo leather after chemical graft copolymerization with ethyl acrylate, butyl acrylate, and 2‐ethyl hexyl acrylate using benzoyl peroxide as an initiator. The optimum conditions for grafting (e.g., monomer and initiator concentrations, temperature and time of grafting, and solvent leather ratio) were extensively investigated. The study achieved outstanding properties for buffalo leather in reduction of water uptake after grafting, especially on using 2‐ethyl hexyl acrylate and butyl acrylate monomers. FT‐IR and solid13C‐NMR for leather before and after grafting confirmed the grafting process.© 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1478–1483, 2003
Effect of molecular weight and degree of deacetylation of chitosan on urea adsorption properties of copper chitosan
Authors: Zhou Yong‐Guo , Yang Yue‐Dong , Guo Xue‐Min , Chen Gui‐Ru
Published: May 2003

Copper chitosan complexes prepared by different specifications of chitosan and copper sulfate were used as urea sorbents. Experimental results showed that the adsorption capacity for urea of copper chitosan increased with an increasing degree of deacetylation and decreasing molecular weight of chitosan. The urea adsorption capacity of copper chitosan was 120.0 mg/g, when 1.0 g of copper chitosan was admitted to 100 mL of a 1300 mg/mL (pH 6.0) urea solution, with chitosan degree of deacetylation of 84.3% and viscosity molecular weight of 6.5 × 105, at 37°C for 8 h. No elution of the copper from the copper chitosan could be detected under the optimal conditions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1520–1523, 2003
Thermal degradation of poly(3‐hydroxybutyrate) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) as studied by TG, TG–FTIR, and Py–GC/MS
Authors: Li Si‐Dong , He Ji‐Dong , Yu Peter H. , Cheung Man Ken
Published: May 2003

The thermal degradation kinetics of poly(3‐hydroxybutyrate) (PHB) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) [poly(HB–HV)] under nitrogen was studied by thermogravimetry (TG). The results show that the thermal degradation temperatures (To, Tp, and Tf) increased with an increasing heating rate (B). Poly(HB–HV) was thermally more stable than PHB because its thermal degradation temperatures, To(0), Tp(0), and Tf(0)—determined by extrapolation to B = 0°C/min—increased by 13°C–15°C over those of PHB. The thermal degradation mechanism of PHB and poly(HB–HV) under nitrogen were investigated with TG–FTIR and Py–GC/MS. The results show that the degradation products of PHB are mainly propene, 2‐butenoic acid, propenyl‐2‐butenoate and butyric‐2‐butenoate; whereas, those of poly(HB–HV) are mainly propene, 2‐butenoic acid, 2‐pentenoic acid, propenyl‐2‐butenoate, propenyl‐2‐pentenoate, butyric‐2‐butenoate, pentanoic‐2‐pentenoate, and CO2. The degradation is probably initiated from the chain scission of the ester linkage. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1530–1536, 2003
Properties of poly(n‐butyl methacrylate) prepared by reverse atom transfer radical polymerization in an aqueous dispersed system
Authors: Peng Hui , Cheng Shiyuan , Feng Linxian
Published: May 2003

Reverse atom transfer radical polymerization (ATRP) of n‐butyl methacrylate (BMA) in waterborne media using Cu(II) complexes with azo initiators (i.e., reverse ATRP) was conducted. The influence of several factors, such as surfactant, catalyst, and reaction time, on the stability of the emulsion, the particle size, the morphology of the emulsion particles, and the control of the polymerization was investigated. The results showed great differences between ATRP and conventional emulsion polymerization, especially the nucleation mechanism and the kinetics. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1542–1547, 2003
Temperature dependence of effective thermal conductivity and thermal diffusivity of treated and untreated polymer composites
Authors: Agarwal Rajni , Saxena N. S. , Sharma Kanan Bala , Thomas S. , Sreekala M. S.
Published: May 2003

Thermal properties, such as thermal conductivity, thermal diffusivity, and specific heat, of treated and untreated oil palm fiber–reinforced PF composites were measured simultaneously at room temperature and normal pressure using the transient plane source (TPS) technique. An increase in thermal conductivity was observed in the fiber‐treated and resin‐treated composites. Surface modifications of fibers by prealkali, potassium permanganate, and peroxide treatments increased the fiber–matrix adhesion by increasing porosity and pore size of the fiber surfaces. The increase in crosslinking enhanced the thermal conductivity of a composite of resin treated with peroxide compared to other composites. Also an attempt was made to explain the temperature dependence of thermal conductivity and thermal diffusivity of amorphous polymer samples using the same technique. It was observed that at the glass‐transition peak of the polymer, thermal conductivity and diffusivity were maximum. Below and above this temperature their values decreased. This has been explained on the basis of predominant scattering processes. An empirical relationship was established for the theoretical prediction of thermal conductivity and diffusivity. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1708–1714, 2003