bluuebunny/crossref_metadata_2025 huggingface dataset:
Every Sparrow That Falls: Understanding Animal Rights Activism as Functional Religion
Authors: Jamison Wesley , Parker James , Wenk Caspar
Published: July 2002

This article reports original research conducted among animal rights activists and elites in Switzerland and the United States, and the finding that activism functioned in activists' and elites' lives like religious belief. The study used reference sampling to select Swiss and American informants. Various articles and activists have identified both latent and manifest quasi-religious components in the contemporary movement. Hence, the research followed upon these data and anecdotes and tested the role of activism in adherents' lives. Using extensive interviews, the research discovered that activists and elites conform to the five necessary components of Yinger's definition of functional religion: intense and memorable conversion experiences, newfound communities of meaning, normative creeds, elaborate and well-defined codes of behavior, and cult formation. The article elaborates on that schema in the context of animal rights belief, elucidates the deeply meaningful role of activism within a filigree of meaning, and concludes that the movement is facing schismatic forces not dissimilar to redemptive and religious movements
NO SEXUAL IMPRINTING ON A RED BILL AS A NOVEL TRAIT
Authors: Hörster Anne , Curio Eberhard , Witte Klaudia
Published: July 2002

Sexual imprinting is one of several known non - genetical, yet social factors which influence mate preferences and might play a role in the evolution of novel traits. We introduced a red bill as a novel trait in a monomorphic estrildid finch, the Javanese mannikin Lonchura leucogastroides. We established three different imprinting groups in which the father only, the mother only or none of the parents had a red bill. After reaching maturity we tested the offspring in double choice tests for a response to birds of the opposite sex with a naturally coloured black bill or with an artificially coloured red bill. Neither males nor females showed a preference for potential mates with a red bill. Males and females raised by a red bill father showed even a strong rejection to conspecifics of the opposite sex with a red bill. This is in contrast to a previous imprinting study in the Javanese mannikin under similar conditions (Witte et al., 2000) in which males and females became sexually imprinted on conspecifics adorned with a red feather on the forehead. It seems that not all kinds of novel traits birds can be sexually imprinted on. We could show in the present study that the red bill is a meaningful trait in female mate choice, i.e. females responded to males with and without a red bill in a similar way as do females imprinted on natural type parents to males with and without other artificial adornments (Witte & Curio, 1999). We could confirm an interaction between the red bill and the natural attractiveness of males as found in a previous study (Witte & Curio, 1999). Our study opens up questions about what traits are really learned and why some traits are not learned during imprinting.
FOREBRAIN SIZE AND INNOVATION RATE IN EUROPEAN BIRDS: FEEDING, NESTING AND CONFOUNDING VARIABLES
Authors: Nicolakakis Nektaria , Lefebvre Louis
Published: July 2002

Previous work has shown a positive correlation between relative forebrain size and feeding innovation frequency, corrected for species number, over different taxonomic groups of birds. Several confounding variables could account for this relationship: ornithologists could notice and report innovations more often in certain taxa because of biased expectations, greater research effort, editorial bias in journals or large population sizes of the taxa. The innovationforebrain correlation could also be spuriously caused by phylogeny or juvenile development mode. We examined these possibilities by entering species number per taxon, population size, number of full length papers, expectations (assessed by a questionnaire), journal source and development mode in multiple regressions that also included relative forebrain size. We did this with and without phylogenetic corrections and tested two behavioural categories, feeding and nesting, where flexibility and learning are clearly thought to differ, but confounds should have similar effects. Through an exhaustive survey covering 30 years in 11 journals, a total of 683 innovations was gathered for the northwestern part of Europe, 507 for feeding and 176 for nesting. Species number per taxon was the only significant confound for both feeding and nesting reports; as predicted, forebrain size was a second significant predictor for feeding innovations, but not for nesting. The frequency of feeding innovations in the short notes of ornithology journals thus appears to be a valid and reliable way to operationalise behavioural flexibility in birds.
INDIVIDUAL AND STATUS RECOGNITION IN THE CRAYFISH, ORCONECTES RUSTICUS: THE EFFECTS OF URINE RELEASE ON FIGHT DYNAMICS
Authors: Schneider Rebecca A. Zulandt , Huber Robert , Moore Paul
Published: July 2002

This study examined individual and status recognition in dyadic interactions between crayfish and determines how blocking the release of urine, a known source of chemical cues, may influence recognition. Behavioral characteristics of agonistic interactions were compared between crayfish pairs that fought each other previously (familiar) and pairs derived from individuals with past status history but no previous experience with one another (unfamiliar). To address the role of urine born chemical cues in recognition, fight dynamics were examined in urine blocked and non-blocked familiar and unfamiliar pairs. Our results indicate the existence of status recognition in crayfish as first fights were longer than second fights and the statistical interaction between fight number and familiar/unfamiliar treatment was similar. Urine cues play a role in social recognition in that fights are longer and more intense when urine cues are absent than when urine cues are present. Communication of behavioral state through urine appears to play an important role in the agonistic interactions of crayfish.
PATTERNS OF INBREEDING AVOIDANCE IN TEMMINCK'S RED COLOBUS
Authors: Starin E.D.
Published: July 2002

Amongst Temminck's red colobus living in the Abuko Nature Reserve, The Gambia, the mechanism for avoiding close inbreeding may depend on the form of inbreeding. Mother-son inbreeding may be avoided through learned behaviour and possibly secondary transfer by the mother. Father-daughter inbreeding may be limited due to transfer and demographic patterns but also aggression directed at the male from the mountee's mother. Maternal brother-sister inbreeding may be avoided through female transfer patterns. Presummed paternal brothersister inbreeding is infrequent but does occur and is not discouraged or avoided.
MATE CHOICE COPYING IN GUPPIES: FEMALES AVOID THE PLACE WHERE THEY SAW COURTSHIP
Authors: Brooks Robert
Published: July 2002

Recent evidence shows that females of many species may copy the mate choice of other females, potentially resulting in the cultural inheritance of mating preferences. The best evidence of mate choice copying has been obtained from studies on guppies, but studies on some guppy populations have failed to find evidence of copying. I report on an experiment in which I found no evidence of mate choice copying in a feral Australian population, either in a traditional 'dichotomous choice tank' design or when females had an opportunity to swim and interact freely with the males. Instead, I found that females tended to avoid the side of the tank on which they had seen a male courting a female. This may not be a mate choice strategy, but possibly a predator avoidance or foraging strategy.
Guarding and Spermatophore Deposition in the Free-Living Eriophyid Mite Vasates Robiniae Nalepa
Authors: Michalska Katarzyna
Published: July 2002

Sex dissociation means that males deposit spermatophores regardless of the presence of females, while females independently seek spermatophores and pick up a sperm. In this study I describe unique behaviour of insects and mites that practice sex dissociation guarding of pre-emergent females (so called quiescent female nymphs). In particular, behaviour which is exhibited by Vasates robiniae males. When competitors were absent in the vicinity of quiescent female nymphs, guarders deposited ca 0.8 spermatophores per hour and placed them around their mates in a manner in which two subsequent spermatophores were situated more frequently within a relatively long distance from each other rather than close to each other. Between the acts of depositions males alternately explored the closest surroundings of the nymphs, at the rate of ca 7.4 times per hour, and became motionless, mostly in bodily contact with the nymphs. Interestingly, while some males guarded until the quiescent female nymphs started moulting, others left their mates at different times before moulting. Prior to departures, males markedly changed their behaviour, more frequently exploring and resting without bodily contact with the nymphs and tended to shorten the time of depositions as well. However, if males stayed with the mates until moulting, the forthcoming time of females emergence did not influence either spermatophore deposition, exploration or the motionless phase of guarding. During and after moulting, guarders also did not persuade or coerce females into picking up a sperm from their spermatophores.
Infectivity of populations of the entomopathogenic nematodes Steinernema feltiae and Heterorhabditis megidis in relation to temperature, age and lipid content
Authors: Menti Hara , Wright Denis , Perry Roland
Published: July 2002

The infectivity of populations of the entomopathogenic nematodes Steinernema feltiae and Heterorhabditis megidis from Greece (GR) and the UK was compared using Galleria mellonella larvae as hosts. Dose-response tests showed that the two Steinernema populations did not differ in their establishment rates but they were more infective than H. megidis UK 211. The temperature range for infectivity was greater than that for development. However, the optimal temperature for infection and development for all populations was 23°C. Infectivity of Steinernema populations was not affected by storage for 12 weeks. However, 12 week-old H. megidis UK 211 infective juveniles (IJ) were less infective than fresh IJ. H. megidis GR showed very low establishment rates at all the doses and temperatures tested, before and after storage. The results are discussed in relation to the nematodes' climatic origin and lipid content. Pouvoir infestant de populations des nématodes entomopathogènes Steinernema feltiae et Heterorhabditis megidis suivant la température, l'âge et le contenu lipidique - Le pouvoir infestant de populations des nématodes entomopathogènes Steinernema feltiae et Heterorhabditis megidis provenant de Grèce et du Royaume Uni a été comparée, utilisant comme hôte Galleria mellonella. Les tests de dose/réaction ont montré que les taux d'établissement des deux populations ne diffèrent pas mais que leur pouvoir infestant était plus élevée que celle de H. megidis UK211. La plage des températures permettant l'infestation était plus étendue que celle relative au développement. Cependant, les températures optimales pour l'infestation et pour le développement étaient l'une et l'autre de 23°C pour toutes les populations. L'infestivité des populations de Steinernema n'a pas été affectée par un stockage de 12 semaines. Les juvéniles infestants de H. megidis UK211 âgés de 12 semaines montraient toutefois une infestivité plus faible que celle d'individus frais. Les specimens de H. megidis provenant de Grèce présentaient - que ce soit avant ou après le stockage - des taux d'établissement très faibles pour toutes les doses et les températures testées. Ces résultats sont discutés en relation avec l'origine climatique et le contenu lipidique des nématodes.
Description of Cryphodera brinkmani n. sp. (Nematoda: Heteroderidae), a parasite of Pinus thunbergii Parlatore from Japan, including a key to the species of the genus Cryphodera Colbran, 1966
Authors: Karssen Gerrit , Aelst Adriaan Van
Published: July 2002

A non cyst-forming heteroderid nematode, Cryphodera brinkmani n. sp., is described and illustrated from the roots of Pinus thunbergii Parlatore from Japan; this new species is characterised by globose female with annulated cuticle and curved projecting neck; stylet 41.5 mum long, with rounded knobs, set off from the shaft; excretory pore located 120 to 157 mum from the anterior end, vulva terminal, with a vulva-anus distance of 49 mum and slightly protruding vulval lips, vulva-anus area ranging from flat to concave, subcrystalline layer present, eggs retained in the body; males rare, with head region set off, two lip annules present, stylet 37.5 mum long, rounded knobs set off, anteriorly slightly pointed, lateral field with three incisures, areolated; second-stage juvenile body 493 mum long, head region set off, four cephalic annuli present, stylet 33.5 mum long, with large anteriorly concave knobs, set off from the shaft, tail 70 mum, tapering towards a pointed hyaline tail terminus of 37 mum in length, areolated lateral field with three incisures, phasmids with a lens-like structure located 6 to 10 mum posterior to the anus. A key for the Cryphodera species is proposed. Description de Cryphodera brinkmani n. sp. (Nematoda: Heteroderidae) parasite de Pinus thunbergii Parlatore au Japon et clef des especes du genre Cryphodera Colbran, 1966 - Un nematode Heteroderide ne formant pas de kyste, Cryphodera brinkmani n. sp., provenant des racines de Pinus thunbergii au Japon, est decrit et illustre; cette nouvelle espece est caracterisee par les femelles globuleuses a cuticule annelee et extremite anterieure courbe, stylet long de 41,5 mum a boutons basaux arrondis bien individualises, pore excreteur situe a 120-157 mum de l'extremite anterieure, vulve terminale (distance vulve-anus 49 mum) et levres vulvaires legerement saillantes, aire perineale plate a concave, presence d'une couche subcristalline, oeufs retenus dans le corps. Les males, rares, ont une region labiale separee du reste du corps, deux anneaux cephaliques, un stylet long de 37,5 mum avec boutons basaux arrondis, bien individualises et legerement pointus anterieurement, des champs lateraux avec trois incisures, areoles. Les juveniles de deuxieme stade, longs de 493 mum, ont une region cephalique separee avec quatre anneaux, un stylet long de 33,5 mum avec des boutons basaux de grande taille, bien individualises et a face anterieure concave, une queue longue de 70 mum, amincie a extremite effilee avec une zone hyaline longue de 37 mum, des champs lateraux marques de trois incisures et areoles, des phasmides a structure lenticulaire situees 6-10 mum posterieurement a l'anus. Une clef pour la determination des especes du genre Cryphodera est proposee.
Ferroelastic orientation states and domain walls in lead phosphate type crystals
Authors: Bismayer U. , Mathes D. , Bosbach D. , Putnis A. , van Tendeloo G. , Novak J. , Salje E. K. H.
Published: July 2002

The monoclinic structural distortion in lead phosphate and lead arsenate is correlated with the ferroelastic phase transition R3̄m → C2/c and R3̄m → P21/c respectively. The resulting domain patterns in the mixed compounds depend on their chemical composition. The intersection of ferroelastic W domain walls with the (100) surface of lead phosphate-arsenate mixed crystals has been imaged using tapping mode atomic force microscopy. Dilution of the strain leads to characteristic surface deformations which deviate from those in pure lead phosphate. In high twinned lead phosphate-arsenate, X-ray diffraction (XRD) was used to show renormalization effects and scattering phenomena stemming from the twin walls. The wall trajectory was found to be independent of chemical variations using transmission electron microscopy.
Calcite precipitation in landfills: an essential product of waste stabilization
Authors: Manning D. A. C.
Published: July 2002

Routine monitoring of landfill leachates has been extended to include characterization of suspended solids recovered by filtration. Calcite is consistently identified as a suspended solid, with less frequent reports of quartz and clays (kaolinite, illite, chlorite). Morphologically, calcite occurs as discrete grains, coatings on quartz sand and as microconcretions. Preliminary stable isotope data for seven samples generally show positive δ13C values (relative to PDB) up to +3.5‰ and δ18O values between −5 and −8‰, consistent with an origin through precipitation from leachate. Geochemical modelling of leachate compositions for the same samples indicates that the leachates are saturated with respect to calcite, and that the degree of supersaturation decreases for older samples. Mass balance considerations show that the proportions of methane and carbon dioxide observed for landfill gas do not reflect the amount of bicarbonate that is potentially available from the anaerobic decomposition of putrescible waste. Overall, putrescible waste has the potential to form a maximum of 1.9 g of calcite for every gram of waste, although values less than this are likely to be achieved in practice. From these differing lines of evidence, there can be no doubt that calcite precipitation should be expected to take place within landfill systems as an essential part of the waste degradation and stabilization process, and should be considered in modelling both gas evolution and carbon emissions.
Phosphoran olivine from Pine Canyon, Piute Co., Utah
Authors: Agrell S. O. , Charnley N. R. , Chinner G. A.
Published: July 2002

Olivines containing up to 6.1 wt.% P2O5 occur in association with apatite and an unnamed NaCaMg phosphate phase. Phosphoran olivine has been recorded only in pallasite meteorites and from one other terrestrial occurrence. The rarity of palpable phosphorus substitution for silicon may be related to the fact that in most terrestrial rocks, phosphorus is incorporated initially, and remains as, apatite; thus phosphorus excess in an undersilicated environment must be uncommon. However the highly capricious distribution of phosphorus in individual olivines from this and the meteoritic occurences suggests disequilibrium, and questions whether phosphoran olivine is ever stable relative to combinations of P-free olivine and phosphate/phosphide minerals.
Crystal chemistry and dissolution of calcium phosphate in dental
enamel
Authors: Dowker S. E. P. , Anderson P. , Elliott J. C. , Gao X. J.
Published: July 2002

The mineral component (at least 95 wt. %) of dental enamel is hydroxyapatite
(hydroxylapatite) with multiple substitutions. The biogenic origin of enamel is
reflected in the unusual ribbon-like morphology of the crystals, which are
extremely elongated in the c-axis direction, and their
organized arrangement within the tissue. The study of enamel dissolution has been
driven by the very high prevalence of dental caries. In enamel caries, the initial
demineralization results in subsurface dissolution of mineral. While the surface
remains intact, reversal of the lesion by remineralization is possible. Problems
of understanding the physico-chemical processes in enamel demineralization include
the general problems concerning the structure and chemistry of apatites formed in
aqueous media. Added to these are the general problem of dissolution in an
inhomogeneous porous medium and the complication that enamel apatite has a
naturally variable composition which changes during demineralization. The use of
model systems in caries research is illustrated by reference to X-ray absorption
studies of enamel and synthetic analogues.
Overexpression of E2F-1 leads to cytokine-independent proliferation and survival in the hematopoietic cell line BaF-B03
Authors: Gala Salvador , Marreiros Alexandra , Stewart Graeme J. , Williamson Peter
Published: July 2002

Cytokine receptors activate signals that regulate the transcription factor E2F-1, which then coordinates the expression of genes essential for DNA synthesis and cell cycle progression. Overexpression of E2F-1 most often induces S-phase entry followed by apoptosis, but in some cell types it leads to continuous proliferation and transformation. Here, it is shown that constitutive expression of E2F-1 promotes cytokine-independent proliferation in the murine pro-B cell line BaF-B03. There was no enhancement of apoptosis following cytokine withdrawal in these cells, despite the presence of intact p53-dependent apoptotic pathways. Notwithstanding the continuous presence of E2F-1, the cell cycle–dependent expression of cyclin A, cyclin B1, cyclin D1, cyclin E, and proliferating-cell nuclear antigen was restored with a pattern equivalent to that associated with cytokine stimulation. These findings provide evidence that, in the absence of cytokine, constitutive expression of E2F-1 can promote cell cycle progression and prevent apoptosis.
Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course
Authors: Tsukasaki Kunihiro , Krebs Johannes , Nagai Kazuhiro , Tomonaga Masao , Koeffler H. Phillip , Bartram Claus R. , Jauch Anna
Published: July 2002

Sixty-four patients with adult T-cell leukemia/lymphoma (ATL; 18 patients with indolent subtype and 46 with aggressive subtype) associated with human T-lymphotropic virus type 1 (HTLV-1) were analyzed using comparative genomic hybridization (CGH). The most frequent observations were gains at chromosomes 14q, 7q, and 3p and losses at chromosomes 6q and 13q. Chromosome imbalances, losses, and gains were more frequently observed in aggressive ATL than in indolent ATL, with significant differences between the 2 ATL subtypes at gains of 1q and 4q. An increased number of chromosomal imbalances was associated with a significantly shorter survival in all patients. A high number of chromosomal losses was associated with a poor prognosis in indolent ATL, whereas the presence of 7q+ was marginally associated with a good prognosis in aggressive ATL. Paired samples (ie, samples obtained at different sites from 4 patients) and sequential samples from 13 patients (from 6 during both chronic disease and acute crisis and from 7 during both acute onset and relapse) were examined by CGH and Southern blotting for HTLV-1. All but 2 paired samples showed differences on CGH assessment. Two chronic/crisis samples showed distinct results regarding both CGH and HTLV-1 integration sites, indicating clonal changes in ATL at crisis. In 11 patients, the finding of identical HTLV-1 sites and clonally related CGH results suggested a common origin of sequential samples. In contrast to chronic/crisis samples, CGH results with all acute/relapse sample pairs showed the presence of clonally related but not evolutional subclones at relapse, thereby suggesting marked chromosomal instability. In summary, clonal diversity is common during progression of ATL, and CGH alterations are associated with clinical course.
Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders
Authors: Canonne-Hergaux François , Levy Joanne E. , Fleming Mark D. , Montross Lynne K. , Andrews Nancy C. , Gros Philippe
Published: July 2002

Iron overload is highly prevalent, but its molecular pathogenesis is poorly understood. Recently, DMT1 was shown to be a major apical iron transporter in absorptive cells of the duodenum. In vivo, it is the only transporter known to be important for the uptake of dietary non-heme iron from the gut lumen. The expression and subcellular localization of DMT1 protein in 3 mouse models of iron overload were examined: hypotransferrinemic (Trfhpx) mice, Hfeknockout mice, and B2m knockout mice. Interestingly, in Trfhpx homozygotes, DMT1 expression was strongly induced in the villus brush border when compared to control animals. This suggests that DMT1 expression is increased in response to iron deficiency in the erythron, even in the setting of systemic iron overload. In contrast, no increase was seen in DMT1 expression in animals with iron overload resembling human hemochromatosis. Therefore, it does not appear that changes in DMT1 levels are primarily responsible for iron loading in hemochromatosis.
Differentiation of Langerhans cells in Langerhans cell histiocytosis
Authors: Geissmann Frederic , Lepelletier Yves , Fraitag Sylvie , Valladeau Jenny , Bodemer Christine , Debré Marianne , Leborgne Michelle , Saeland Sem , Brousse Nicole
Published: July 2002

Langerhans cell histiocytosis (LCH) consists of lesions composed of cells with a dendritic Langerhans cell (LC) phenotype. The clinical course of LCH ranges from spontaneous resolution to a chronic and sometimes lethal disease. We studied 25 patients with various clinical forms of the disease. In bone and chronic lesions, LCH cells had immature phenotype and function. They coexpressed LC antigens CD1a and Langerin together with monocyte antigens CD68 and CD14. Class II antigens were intracellular and LCH cells almost never expressed CD83 or CD86 or dendritic cell (DC)–Lamp, despite their CD40 expression. Consistently, LCH cells sorted from bone lesions (eosinophilic granuloma) poorly stimulated allogeneic T-cell proliferation in vitro. Strikingly, however, in vitro treatment with CD40L induced the expression of membrane class II and CD86 and strongly increased LCH cell allostimulatory activity to a level similar to that of mature DCs. Numerous interleukin-10–positive (IL-10+), Langerin−, and CD68+ macrophages were found within bone and lymph node lesions. In patients with self-healing and/or isolated cutaneous disease, LCH cells had a more mature phenotype. LCH cells were frequently CD14− and CD86+, and macrophages were rare or absent, as were IL-10–expressing cells. We conclude that LCH cells in the bone and/or chronic forms of the disease accumulate within the tissues in an immature state and that most probably result from extrinsic signals and may be induced to differentiate toward mature DCs after CD40 triggering. Drugs that enhance the in vivo maturation of these immature DCs, or that induce their death, may be of therapeutic benefit.
Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome
Authors: Savoia Anna , Balduini Carlo L. , Savino Maria , Noris Patrizia , Del Vecchio Maria , Perrotta Silverio , Belletti Simona , Poggi Vincenzo , Iolascon Achille
Published: July 2002

A form of autosomal dominant macrothrombocytopenia is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count. Because this condition has so far received little attention, patients are subject to misdiagnosis and inappropriate therapy. To identify the molecular basis of this disease, 12 Italian families were studied by linkage analysis and mutation screening. Flow cytometry evaluations of platelet membrane glycoproteins (GPs) were also performed. Linkage analysis in 2 large families localized the gene to chromosome 17p, in an interval containing an excellent candidate, the GPIbα gene. GPIbα, together with other proteins, constitutes the plasma von Willebrand factor (vWF) receptor, which is altered in Bernard-Soulier syndrome (BSS). In 6 of 12 families, a heterozygous Ala156Val missense substitution was identified. Platelet membrane GP studies were performed in 10 patients. Eight were distinguished by a reduction of GPs comparable to that found in a BSS heterozygous condition, whereas the other 2, without the Ala156Val mutation, had a normal content of platelet GPs. In conclusion, the current study provides evidence that most (10 of 12) patients with an original diagnosis of autosomal dominant macrothrombocytopenia shared clinical and molecular features with the heterozygous BSS phenotype. The remaining 2 affected subjects represented patients with “true” autosomal dominant macrothrombocytopenia; the GPIb/IX/V complex was normally distributed on the surface of their platelets. Thus, the diagnosis of heterozygous BSS must always be suspected in patients with inherited thrombocytopenia and platelet macrocytosis.
The interphase microtubule damage checkpoint defines an S-phase commitment point and does not requirep21waf-1
Authors: Mantel Charlie R. , Braun Stephen E. , Lee Younghee , Kim Young-June , Broxmeyer Hal E.
Published: July 2002

Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G1 phase of the cell cycle (G1MTC) for which little is known. The present study shows that the G1MTC is intact in activated T lymphocytes from mice with the p21waf-1 gene deleted. However, p21waf-1 gene deletion does affect the ratio of cells that arrest at the G1MTC and the spindle checkpoint after MTD. The G1MTC arrests T lymphocytes in G1 prior to cdc2 up-regulation and prior to G1arrest by p21waf-1. Once cells have progressed past the G1MTC, they are committed to chromosome replication and metaphase progression, even with extreme MTD. The G1MTC is also present in a human myeloid cell line deficient in p21waf-1gene expression. The p21-independent G1MTC may be important in cellular responses to MTD such as those induced by drugs used to treat cancer.
Human thymus contains 2 distinct dendritic cell populations
Authors: Vandenabeele Stéphane , Hochrein Hubertus , Mavaddat Nasim , Winkel Ken , Shortman Ken
Published: July 2002

In this study, 2 distinct populations of mature dendritic cells (DCs) were identified in the human thymus. The major population is CD11b−, CD11c+, and CD45ROlowand does not express myeloid-related markers. It displays all the characteristics of mature DCs with a typical dendritic morphology, high surface levels of HLA-DR, CD40, CD83, and CD86, and expression of DC–lysosome-associated membrane glycoprotein messenger RNA (mRNA). In addition, CD11b− thymic DCs do not express macrophage inflammatory protein-1α (MIP-1α) mRNA, but express thymus-expressed chemokine (TECK) mRNA and are able to secrete bioactive interleukin 12 (IL-12) upon stimulation. In contrast, the minor and variable thymic DC population is CD11b+, CD11chigh, and CD45ROhigh and comprises CD83+CD14− mature and CD83−CD14+ immature DCs. It expresses macrophage-colony stimulating factor receptor, MIP-1α mRNA and high amounts of decysin mRNA after CD40 activation, but does not express TECK and is a weak bioactive IL-12 producer. Also identified were the IL-3Rαhigh plasmacytoid cells, which are present in the thymic cortex and medulla. Upon culture with IL-3, granulocyte/macrophage–colony stimulating factor, and CD40 ligand, the plasmacytoid cells can adopt a phenotype resembling that of freshly isolated CD11b− thymic DCs. However, these plasmacytoid-derived DCs fail to secrete bioactive IL-12; therefore, conclusions cannot be made about a direct relation between thymic plasmacytoid cells and CD11b− DCs. Whereas CD11b+ thymic DCs appear to be related to tonsillar germinal-center DCs, the major CD11b− IL-12–secreting human thymus DC population has similarities to mouse CD11b− CD8+ DCs.
Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy
Authors: Choufani Elie B. , Sanchorawala Vaishali , Ernst Timothy , Quillen Karen , Skinner Martha , Wright Daniel G. , Seldin David C.
Published: July 2002

Acquired deficiency of factor X occurs in patients with systemic amyloid light-chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more frequent and severe in the 12 patients below 25% of normal; 2 episodes were fatal. Ten factor X–deficient patients received high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Of 7 patients alive 1 year after treatment, 4 had a complete hematologic response, and all 4 experienced improvement in their factor X levels. One of 2 additional patients with partial hematologic responses had improvement in factor X. Thus, aggressive treatment of the underlying plasma cell dyscrasia in AL amyloidosis can lead to the amelioration of amyloid-related factor X deficiency.
Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol
Authors: Noy Ariela , Verma Ravi , Glenn Martha , Maslak Peter , Rahman Zia U. , Keenan James R. , Weiss Mark , Filippa Daniel , Zelenetz Andrew D.
Published: July 2002

Patient–tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 105cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m2 per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m2). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5–CD19 dual staining and κ–λ clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry.
Expression and characterization of von Willebrand factor dimerization defects in different types of von Willebrand disease
Authors: Schneppenheim Reinhard , Budde Ulrich , Obser Tobias , Brassard Jacqueline , Mainusch Kerstin , Ruggeri Zaverio M. , Schneppenheim Sonja , Schwaab Rainer , Oldenburg Johannes
Published: July 2002

Dimerization defects of von Willebrand factor (vWF) protomers underlie von Willebrand disease (vWD) type 2A, subtype IID (vWD 2A/IID), and corresponding mutations have been identified at the 3′ end of the vWF gene in exon 52. This study identified and expressed 2 additional mutations in this region, a homozygous defect in a patient with vWD type 3 (C2754W) and a heterozygous frameshift mutation (8566delC) in a patient with vWD type 2A, subtype IIE. Both mutations involve cysteine residues that we propose are possibly essential for dimerization. To prove this hypothesis, transient recombinant expression of each of the 2 mutations introduced in the carboxy-terminal vWF fragment II and in the complete vWF complementary DNA, respectively, were carried out in COS-7 cells and compared with expression of vWD 2A/IID mutation C2773R and the wild-type (WT) sequence in COS-7 cells. Recombinant WT vWF fragment II assembled correctly into a dimer, whereas recombinant mutant fragments were monomeric. Homozygous expression of recombinant mutant full-length vWF resulted in additional dimers, probably through disulfide bonding at the amino-terminal multimerization site, whereas recombinant WT vWF correctly assembled into multimers. Coexpression of recombinant mutant and recombinant WT vWF reproduced the multimer patterns observed in heterozygous individuals. Our results suggest that a common defect of vWF biosynthesis—lack of vWF dimerization—may cause diverse types and subtypes of vWD. We also confirmed previous studies that found that disulfide bonding at the vWF amino-terminal is independent of dimerization at the vWF carboxy-terminal.
Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle
Authors: Wright Douglas E. , Cheshier Samuel H. , Wagers Amy J. , Randall Troy D. , Christensen Julie L. , Weissman Irving L.
Published: July 2002

Cytokine-mobilized peripheral blood hematopoietic stem cells (MPB HSC) are widely used for transplantation in the treatment of malignancies, but the mechanism of HSC mobilization is unclear. Although many HSC in bone marrow (BM) cycle rapidly and expand their numbers in response to cytoreductive agents, such as cyclophosphamide (CY), and cytokines, such as granulocyte colony-stimulating factor (G-CSF), MPB HSC are almost all in the G0 or G1phase of the cell cycle. This has raised the question of whether a subset of noncycling BM HSC is selectively released, or whether cycling BM HSC are mobilized after M phase, but before the next S phase of the cell cycle. To distinguish between these possibilities, mice were treated with one dose of CY followed by daily doses of G-CSF, and dividing cells were marked by administration of bromodeoxyuridine (BrdU) during the interval that BM HSC are expanding. After CY and 4 days of G-CSF, 98.5% of the 2n DNA content long-term repopulating MPB (LT)-HSC stained positively for BrdU, and therefore derived from cells that divided during the treatment interval. Next, LT-HSC from mice previously treated with a single dose of CY, which kills cycling cells, and 3 daily doses of G-CSF, were nearly all killed by a second dose of CY, suggesting that CY/G-CSF causes virtually all LT-HSC to cycle. Analysis of cyclin D2 messenger RNA (mRNA) expression and total RNA content of MPB HSC suggests that these cells are mostly in G1 phase. After CY/G-CSF treatment, virtually all BM LT-HSC enter the cell cycle; some of these HSC then migrate into the blood, specifically after M phase, and are rapidly recruited to particular hematopoietic organs.
Expression and colocalization of cytokeratin 1 and urokinase plasminogen activator receptor on endothelial cells
Authors: Mahdi Fakhri , Shariat-Madar Zia , Todd Robert F. , Figueroa Carlos D. , Schmaier Alvin H.
Published: July 2002

The cellular localization of human cytokeratin 1 (CK1), urokinase plasminogen activator receptor (uPAR), and gC1qR, high-molecular-weight kininogen (HK)-binding proteins on endothelial cells, was determined. CK1 was found on the external membrane of nonpermeabilized endothelial cells by immunoperoxidase staining, immunofluorescence, and transmission electron microscopy using immunogold. Human umbilical vein endothelial cells (HUVECs) had 7.2 ± 0.2 × 104specific CK1 membrane sites/cell by125I-F(ab′)2 anti-CK1 antibody binding. Flow cytometry studies confirmed the presence of CK1, uPAR, and gC1qR on HUVECs. On laser scanning confocal microscopy and transmission electron microscopy, CK1 and uPAR, but not gC1qR, colocalized on the cell surface of HUVECs. The HUVEC surface distribution of these proteins was distinctly different from that for von Willebrand factor. In competitive inhibition experiments, anti-CK1, anti-uPAR, or anti-gC1qR blocked both biotin-HK binding and prekallikrein (PK) activation on HUVECs with an inhibitory concentration of 50% (IC50) of 300 to 350 nM, 50 to 60 nM, or 35 to 100 nM, respectively. Also, antibodies to uPAR and gC1qR each inhibited 86% of kallikrein-mediated, 2-chain urokinase plasminogen activation, whereas antibodies to CK1 only inhibited 24% of plasminogen activation. On HUVECs, CK1 and uPAR, but not gC1qR, colocalized to be a multiprotein receptor complex for HK binding, PK activation, and 2-chain urokinase plasminogen activation.
Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation
Authors: van Spriel Annemiek B. , Leusen Jeanette H. W. , van Egmond Marjolein , Dijkman Henry B. P. M. , Assmann Karel J. M. , Mayadas Tanya N. , van de Winkel Jan G. J.
Published: July 2002

Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated lysis of tumor cells was characterized by studying normal human PMNs, Mac-1–deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular cytotoxicity (ADCC) was abrogated in Mac-1−/− PMNs and in human PMNs blocked with anti–Mac-1 monoclonal Ab (mAb). Mac-1−/− PMNs were unable to spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser scanning and electron microscopy revealed a striking difference in immunologic synapse formation between Mac-1−/− and wild-type PMNs. Also, respiratory burst activity could be measured outside membrane-enclosed compartments by using Mac-1−/− PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In summary, these data document an absolute requirement of Mac-1 for FcR-mediated PMN cytotoxicity toward tumor targets. Mac-1−/− PMNs exhibit defective spreading on Ab-coated targets, impaired formation of immunologic synapses, and absent tumor cytolysis.
Cytokine-regulated expression of survivinin myeloid leukemia
Authors: Carter Bing Z. , Milella Michele , Altieri Dario C. , Andreeff Michael
Published: July 2002

Survivin, a member of the inhibitors-of-apoptosis gene family, is expressed in a cell-cycle–dependent manner in all the most common cancers but not in normal differentiated adult tissues.Survivin expression and regulation were examined in acute myeloid leukemia (AML). Survivin was detected by Western blot analysis in all myeloid leukemia cell lines and in 16 of 18 primary AML samples tested. In contrast, normal CD34+ cells and normal peripheral blood mononuclear cells expressed no or very low levels of survivin. Cytokine stimulation increasedsurvivin expression in leukemic cell lines and in primary AML samples. In cultured primary samples, single-cytokine stimulation substantially increased survivin expression in comparison with control cells, and the combination of G-CSF, GM-CSF, and SCF increased survivin levels even further. Conversely, all-trans retinoic acid significantly decreased survivinprotein levels in HL-60, OCI-AML3, and NB-4 cells within 96 hours, parallel to the induction of myelomonocytic differentiation. Using selective pharmacologic inhibitors, the differential involvement of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol-3 kinase (PI3K) pathways were demonstrated in the regulation of survivin expression. The MEK inhibitor PD98059 down-regulated survivin expression in both resting and GM-CSF–stimulated OCI-AML3 cells, whereas the PI3K inhibitor LY294002 inhibited survivin expression only on GM-CSF stimulation. In conclusion, these results demonstrate thatsurvivin is highly expressed and cytokine-regulated in myeloid leukemias and suggest that hematopoietic cytokines exert their antiapoptotic and mitogenic effects, at least in part, by increasing survivin levels.
Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura
Authors: Kuwana Masataka , Kaburaki Junichi , Kitasato Hidero , Kato Miyako , Kawai Shinichi , Kawakami Yutaka , Ikeda Yasuo
Published: July 2002

It was recently reported that autoreactive CD4+ T cells to glycoprotein IIb-IIIa (GPIIb-IIIa) mediate antiplatelet autoantibody production in patients with immune thrombocytopenic purpura (ITP). To further examine the antigenic specificity of the GPIIb-IIIa–reactive T cells, 6 recombinant fragments encoding different portions of GPIIbα or GPIIIa were generated and tested for their ability to stimulate antigen-specific T-cell proliferation and anti–GPIIb-IIIa antibody production in vitro. T cells from the peripheral blood of 25 patients with ITP and 10 healthy donors proliferated in response to recombinant GPIIb-IIIa fragments in various combinations. The amino-terminal portions of both GPIIbα and GPIIIa (IIbα18-259 and IIIa22-262) were frequently recognized (60% and 64%, respectively) compared with other fragments (4%-28%) in patients with ITP, but this tendency was not detected in healthy donors. In subsequent analyses in patients with ITP, T-cell reactivities to IIbα18-259 and IIIa22-262 were consistently detected, whereas those to other fragments were sometimes lost. In vitro antigenic stimulation of peripheral blood mononuclear cells with IIbα18-259 or IIIa22-262 promoted the synthesis of anti–GPIIb-IIIa antibodies in patients with ITP, but not in healthy donors. Of 15 CD4+ T-cell lines specific for platelet-derived GPIIb-IIIa generated from 5 patients with ITP, 13 lines recognized IIbα18-259, IIIa22-262, or both. T-cell lines reactive to IIbα18-259 or IIIa22-262 promoted the production of anti–GPIIb-IIIa antibodies that were capable of binding to normal platelet surfaces. These results indicate that the immunodominant epitopes recognized by pathogenic CD4+ T cells in patients with ITP are located within the amino-terminal portions of both GPIIbα and GPIIIa.
p16

INK4a
andp15INK4b gene methylations in plasma cells from monoclonal gammopathy of undetermined significance
Authors: Guillerm Gaëlle , Gyan Emmanuel , Wolowiec Darius , Facon Thierry , Avet-Loiseau Hervé , Kuliczkowski Kazimierz , Bauters Francis , Fenaux Pierre , Quesnel Bruno
Published: July 2002

p15INK4b and p16INK4a proteins are cell cycle regulators involved in the inhibition of G1 phase progression. High frequency of methylation of both genes has been reported in multiple myeloma (MM), but it remains to be determined how and when these alterations contribute to tumorigenesis. Monoclonal gammopathy of undetermined significance (MGUS) represents an early disease stage in a fraction of MMs. Plasma cells from 33 patients with MGUS and 33 patients with MM were isolated and analyzed forp15INK4b and p16INK4amethylation by methylation-specific polymerase chain reaction. Selective methylation was found in 19% forp16INK4a, 36% forp15INK4b, and 6.5% for both genes in MGUS, and frequencies were similar in MM suggesting that methylation of these genes is an early event, not associated with transition from MGUS to MM. p15INK4b andp16INK4a gene methylation might contribute to immortalization of plasma cells rather than malignant transformation in the natural history of MM.