bluuebunny/crossref_metadata_2025 huggingface dataset:
Predation and Cathemerality
Authors: Colquhoun Ian C.
Published: January 2006

The removal, or absence, of predatory species could be a contributing proximate factor to the rise of primate cathemerality. But predators themselves can also be cathemeral, so cathemerality could well be an evolutionary stable strategy. From a comparative perspective, it appears that the effect of predatory species cannot provide a unitary explanation for cathemerality. Varying distributions and population densities of predators, especially raptors, may be key factors in owl monkey(Aotus)cathemerality, but temperature and lunar cycle variation have also been implicated. In Madagascar, while raptors are potential predators of lemur species, the cathemerality ofEulemurspecies coincides with that of the fossa(Cryptoprocta ferox), a major predatory threat to lemurs. Thus, lemurid cathemerality may be more parsimoniously explained as an evolutionary stable strategy.
The Evolution of Cathemerality in Primates and Other Mammals: A Comparative and Chronoecological Approach
Authors: Curtis D.J. , Rasmussen M.A.
Published: January 2006

Non-primate mammalian activity cycles are highly variable across and within taxonomic groups. In contrast, the order Primates has historically been recognized as displaying a diurnal-nocturnal dichotomy that mapped, for the most part, onto the taxonomic division between haplorhines and strepsirhines. However, it has become clear over the past two decades that activity cycles in primates are not quite so clear cut. Some primate species – like many large herbivorous mammals, mustelids, microtine rodents, and shrews – exhibit activity both at night and during the day. This activity pattern is often polyphasic or ultradian (several short activity bouts per 24-hour period), in contrast to the generally monophasic pattern (one long bout of activity per 24-hour period) observed in diurnal and nocturnal mammals. Alternatively, it can vary on a seasonal basis, with nocturnal activity exhibited during one season, and diurnal activity during the other season. The term now generally employed to describe the exploitation of both diurnal and nocturnal phases in primates is ‘cathemeral’. Cathemerality has been documented in one haplorhine, the owl monkey,Aotus azarai, in the Paraguayan and Argentinian Chaco and in several Malagasy strepsirhines, includingEulemurspp.,Hapalemursp. andLemur catta.In this paper, we review patterns of day-night activity in primates and other mammals and investigate the potential ecological and physiological bases underlying such 24-hour activity. Secondly, we will consider the role of cathemerality in primate evolution.
Neuropsychological Performance in Mild Cognitive Impairment with and without Apathy
Authors: Robert Philippe H. , Berr Claudine , Volteau Magali , Bertogliati Christelle , Benoit Michel , Mahieux Florence , Legrain Sylvie , Dubois Bruno
Published: January 2006

Objective: To investigate the neuropsychological characteristics of patients diagnosed with mild cognitive impairment (MCI) with and without apathy. Methods: A cohort of 245 MCI patients (mean age = 72 ± 5.5 years; mean MMSE = 27.5 ± 1.3) was divided into two subgroups according to their Apathy Inventory score and underwent an extensive neuropsychological battery. Results: There were 94 (38.4%) patients with and 151 (61.6%) patients without apathy. At baseline the apathetic subgroup had a significantly lower total score on the free and cued selective reminding test (FCSR). Furthermore, the apathetic subgroup showed a significant deterioration in FCSR total recall score between baseline and the 1-year assessment. In conclusion, the presence of apathy in MCI patients is not associated with frontal task performance but with a higher degree of memory impairment.
Noninvasive Ventilation in Childhood Acute Neuromuscular Respiratory Failure: A Pilot Study
Authors: Piastra M. , Antonelli M. , Caresta E. , Chiaretti A. , Polidori G. , Conti G.
Published: January 2006

Background: Over a 36-month study period, 10 nonconsecutive neuromuscular pediatric patients (6 infants, mean age 10.16 months, and 4 children, mean age 9.3 years) presenting with acute respiratory failure (ARF) were treated by noninvasive positive pressure ventilation (NPPV). All patients required immediate respiratory support and fulfilled our intubation criteria. Objective: The aim of the study was to verify if early NPPV was able to avoid endotracheal intubation and to improve both oxygenation and ventilation within 24 h from admission in this clinical setting. Patients andMethods: A prospective pilot study was carried out on neuromuscular patients admitted to the pediatric intensive care unit (PICU) of the Catholic University of Rome because of ARF and managed exclusively with NPPV for at least 24 h following admission. All patients were treated using a flow-triggered mechanical ventilator through a face mask or using the new helmet interface. Results: Eight patients were successfully ventilated during the observation period and 2 early failures occurred. Among children undergoing face mask NPPV, the PaO2/FiO2 ratio increased from a median value of 75 (range 48–149) to 240 (range 133–385; p < 0.001) and 328 (range 180–371; p < 0.001) at selected time points (3 and 12 h after NPPV introduction, respectively); the alveolar-to-arterial oxygenation difference showed a similar trend, i.e. decreasing from a median value of 589 (range 213–659) to 128 (range 62–527; p < 0.01) and 69 (range 45–207; p < 0.001), respectively. Hypercarbic ARF resolved within 6 h from admission even in the most severe cases. Conclusions: NPPV was a safe and effective first-line therapeutic approach in hypoxemic ARF children/infants with neuromuscular disease. It seems of importance to identify children with neuromuscular disorders who may be able to achieve residual ventilator-free breathing and to perform an NPPV trial avoiding tracheal intubation. Life-threatening respiratory distress and very young age should not preclude NPPV application in the PICU setting. The new helmet interface represents a promising tool for noninvasive ventilation in older children.
Neuroanatomical Distribution of Cannabinoid Receptor Gene Expression in the Brain of the Rough-Skinned Newt, Taricha granulosa
Authors: Hollis David M. , Coddington Emma J. , Moore Frank L.
Published: January 2006

Type I cannabinoid receptor (CB1) is a G-protein coupled receptor with a widespread distribution in the central nervous system in mammals. In a urodele amphibian, the rough-skinned newt (Taricha granulosa), recent evidence indicates that endogenous cannabinoids (endocannabinoids) mediate behavioral responses to acute stress and electrophysiological responses to corticosterone. To identify possible sites of action for endocannabinoids, in situ hybridization using a gene and species specific cRNA probe was used to label CB1 mRNA in brains of male T. granulosa. Labeling of CB1 mRNA in the telencephalon was observed in the olfactory bulb and all areas of the pallium, as well as the bed nucleus of the stria terminalis and nucleus amygdalae dorsolateralis. The labeling of CB1 mRNA was also found in regions of the preoptic area, thalamus, midbrain tegmentum and tectum, cerebellum, and the stratum griseum of the hindbrain. A notable difference in CB1 labeling between this amphibian and mammals is the abundance of labeling in areas associated with olfaction (anterior olfactory nuclei, nucleus amygdalae dorsolateralis, and lateral pallium), which hints that endocannabinoids might modulate responses to odors as well as pheromones. This widespread distribution of CB1 labeling, particularly in sensory and motor control centers, fits with prior results showing that endocannabinoids modulate sensorimotor processing and behavioral output in this species. The distribution of CB1 in the brain of T. granulosa was in many of the same sites previously observed in the brain of the anuran amphibian, Xenopus laevis, as well as those of different species of mammals, suggesting that endocannabinoid signaling pathways are conserved.
Behavioral Flexibility Positively Correlated with Relative Brain Volume in Predatory Bats
Authors: Ratcliffe John M. , Fenton M. Brock , Shettleworth Sara J.
Published: January 2006

We investigated the potential relationships between foraging strategies and relative brain and brain region volumes in predatory (animal-eating) echolocating bats. The species we considered represent the ancestral state for the order and approximately 70% of living bat species. The two dominant foraging strategies used by echolocating predatory bats are substrate-gleaning (taking prey from surfaces) and aerial hawking (taking airborne prey). We used species-specific behavioral, morphological, and ecological data to classify each of 59 predatory species as one of the following: (1) ground gleaning, (2) behaviorally flexible (i.e., known to both glean and hawk prey), (3) clutter tolerant aerial hawking, or (4) open-space aerial hawking. In analyses using both species level data and phylogenetically independent contrasts, relative brain size was larger in behaviorally flexible species. Further, relative neocortex volume was significantly reduced in bats that aerially hawk prey primarily in open spaces. Conversely, our foraging behavior index did not account for variability in hippocampus and inferior colliculus volume and we discuss these results in the context of past research.
Primary Extranodal NK/T Cell Lymphoma (‘Nasal Type’) of the Endometrium: Report of an Unusual Case Diagnosed at Autopsy
Authors: Briese Juliane , Noack Frank , Harland Albrecht , Horny Hans-Peter
Published: January 2006

Primary natural killer (NK)/T cell lymphoma of the female genital tract is extremely rare. We here report the case of a ‘nasal type’ NK/T cell lymphoma arising in the uterus. The diagnosis was established only at autopsy.
Insulin-Like Growth Factor-1 Increases Intracellular Calcium Concentration in Human Primary Neuroendocrine Pancreatic Tumor Cells and a Pancreatic Neuroendocrine Tumor Cell Line (BON-1) via R-Type Ca2+ Channels and Regulates Chromogranin A Secretion in BON-1 Cells
Authors: Mergler Stefan , Strauss Olaf , Strowski Mathias , Prada Javier , Drost Adriana , Langrehr Jan , Neuhaus Peter , Wiedenmann Bertram , Ploeckinger Ursula
Published: January 2006

Insulin-like growth factor 1 (IGF-1) is a potent mitogenic and secretory factor that acts on voltage operated Ca2+ channels (VOCCs). VOCCs are categorized into L-type channels (CaV1.1–1.4), P/Q-type channels (CaV2.1), N-type channels (CaV2.2), R-type channels (CaV2.3), and T-type channels (CaV3.1–3.3). Aside from regulating membrane excitability, VOCCs influence chromogranin A (CgA) secretion in neuroendocrine tumor (NET) cells. It is not known, whether VOCCs play a role in the IGF-1-dependent regulation of CgA secretion in NET cells. We therefore studied the effects of IGF-1 on individual VOCC subtypes and characterized their role in mediating IGF-1-dependent regulation of CgA secretion in NET cells. Using specific modulators of VOCC subtypes, we identified the functional expression of L-, N-, P/Q- and R-type channels in primary as well as permanent models of NET. The IGF-1-induced intracellular Ca2+ increase in NET cells was mainly due to the activation of R-type channel activity. The effects on intracellular calcium, observed in whole-cell patch-clamp recordings and fluorescence imaging, were partially blocked by the specific R-type channel blocker SNX-482 and antisense oligonucleotides against the α1 subunit of this channel. IGF-1 potently induced CgA secretion. The effect of IGF-1 was reduced by both, inhibition of R-type channel activity and a reduction of R-type channel expression using antisense oligonucleotides. Since R-type channels exist in NET cells and couple to both, IGF-1 receptor signaling as well as CgA secretion, pharmacological interference with R-type channels may represent a new therapeutic option by blocking Ca2+ signaling thereby abrogating IGF-1-dependent hypersecretion in NET disease.
Post-Operative Delirium Is Associated with Poor Cognitive Outcome and Dementia
Authors: Wacker Priscilla , Nunes Paula V. , Cabrita Henrique , Forlenza Orestes V.
Published: January 2006

The objective of the present study is to evaluate the association between the occurrence of delirium and the cognitive outcome in elderly subjects. Hospital files of 572 patients who underwent hip or knee replacement between 1998 and 2004 were examined. A sample of 90 elderly subjects (31 with evidence of post-operative delirium), non-demented at baseline, was screened for cognitive decline and dementia. Diagnosis of dementia was highly associated with the occurrence of delirium. The relative risk for the diagnosis of dementia among subjects with previous history of delirium, according to the IQcode screening, was 10.5 (95% CI: 3.3–33.2). Such patients had a significantly higher mean IQcode score (3.75) as compared to controls (3.1; p < 0.001). Cognitive functions most affected in these patients were memory, orientation and abstract thinking. We conclude that the occurrence of post-operative delirium in cognitively unimpaired elderly subjects is associated with a worse cognitive outcome and an increased risk of dementia.
uPAR (CD87) as a Biocompatibility Marker of Dialysis Membrane
Authors: Sohka Takayuki , Ohno Takeshi , Ichinose Mayuri , Okonogi Hideo , Kawaguchi Yoshindo , Hosoya Tatsuo , Nakamura Kazuyoshi , Kataoka Eiko , Suzuki Mari , Koremoto Masahide , Sumita Masaya , Shirai Takasi , Kasai Kenji
Published: January 2006

Background/Aims: Hemodialysis (HD) therapy may lead to functional changes in patient leukocytes. For example, the upregulation of inflammatory cytokines, such as IL-1β and TNFα, has been well characterized. However, these findings do not explain the entire response of leukocytes in HD. In this study, we carried out a comprehensive gene expression analysis in leukocytes treated with various dialysis membranes using DNA microarrays. The identified gene has the potential to be a new marker for testing dialysis membrane biocompatibility. Methods: Gene expression profiles were compared between a group of leukocytes treated with various dialysis membranes and an untreated group by using DNA microarray analysis. Expression was confirmed by quantitative RT-PCR. The expression of the gene product (leukocyte surface protein) was examined in 20 chronic HD patients by flow cytometry. Results: In addition to the inflammatory cytokines, the urokinase plasminogen activator receptor (uPAR or CD87) gene was induced in leukocytes treated with each dialysis membrane. The extent of induction depended on the membrane’s material composition. The expression of the uPAR (CD87) protein on leukocytes was markedly increased in patients undergoing dialysis therapy. The magnitude of uPAR (CD87) protein expression was correlated with clinical findings, i.e., the degree of leukopenia and the expression of adhesion molecules. Conclusions: The gene and protein expression of uPAR (CD87) depended on the dialysis membrane material and correlated closely with clinical findings. These results suggest that uPAR has the potential to serve as a marker not only for clinical use but also for the development of new dialysis membranes.
Power Frequency Magnetic Fields Increase Cell Proliferation in the Mammary Gland of Female Fischer 344 Rats but Not Various Other Rat Strains or Substrains
Authors: Fedrowitz Maren , Löscher Wolfgang
Published: January 2006

Epidemiological data have raised concerns about the relationship between exposure to power frequency magnetic fields (MFs) and breast cancer. We have shown previously that 50-Hz MFs at microtesla flux densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF exposure results in an enhanced proliferative activity of the mammary epithelium of SD rats, which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model. Comparison of different SD substrains indicated that the genetic background plays a pivotal role in these effects of MF exposure. This prompted us to compare the effects of MF exposure (100 µT, 2 weeks) on cell proliferation in the mammary gland in eight different strains and substrains of outbred and inbred rats. Proliferation of epithelial cells in the mammary tissue and adjacent skin was examined by labeling proliferating cells with bromodeoxyuridine (BrdU). In addition to the MF-sensitive SD substrain (SD1) previously used in our experiments, Fischer 344 rats were the only strain in which MF exposure significantly enhanced BrdU labeling in the mammary epithelium, indicating a marked increase in cell proliferation. The MF-induced increase in BrdU labeling in Fischer 344 rats was similar to that seen after DMBA application. Furthermore, whole mount analysis of mammary tissue from Fischer 344 rats demonstrated that MF exposure increased the number of terminal end buds, i.e. the site of origin of mammary carcinomas. By comparison with MF-insensitive inbred rat strains, Fischer 344 rats may serve to evaluate the genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure.
Potent Bystander Effect in Suicide Gene Therapy Using Neural Stem Cells Transduced with Herpes Simplex Virus Thymidine Kinase Gene
Authors: Li Shaoyi , Tokuyama Tsutomu , Yamamoto Junkoh , Koide Masayo , Yokota Naoki , Namba Hiroki
Published: January 2006

Objective: The herpes simplex virus thymidine kinase (HSVtk)/ganciclovir suicide gene therapy system has been considered as one of the most promising therapeutic strategies for malignant gliomas. We have been using HSVtk gene-transduced neural stem cells (NSCtk) that possess an ability to migrate toward a tumor mass for the treatment of experimental brain tumors. In the present study, we evaluated the potency of anti-tumor effect mediated by the bystander effect between NSCtk and C6 glioma cells in the HSVtk/ganciclovir suicide gene therapy system. Methods: NSCtk and C6 glioma cells were mixed at various ratios (NSCtk:C6 cell ratios of 1:1 to 1:64) and the bystander effect was evaluated both under in vitro and in vivo conditions. Results: In vitro co-culture experiment showed a complete tumor growth inhibition at the NSCtk:C6 ratios as low as 1:16. In vivo co-implantation study in the rat brain showed no visible tumors at the NSCtk:C6 ratios as low as 1:16 and all those rats survived more than 100 days. Conclusion: The results clearly demonstrated an extremely potent bystander effect between NSCtk and C6 cells, and the minimum number of NSCtk cells needed for the treatment of tumors was roughly estimated.
Autosomal-Dominant Isolated Growth Hormone Deficiency (IGHD Type II) with Normal GH-1 Gene
Authors: Fintini Danilo , Salvatori Roberto , Salemi Souzan , Otten Barto , Ubertini GraziaMaria , Cambiaso Paola , Mullis Primus-E.
Published: January 2006

Background: Autosomal-dominant isolated GH deficiency (IGHD) is a rare disorder that is commonly believed to be due to heterozygous mutations in the GH-1 gene (GH-1). These mutations cause the production of a protein that affects the release of the product of the normal allele. Rarely, heterozygous mutations in the gene encoding for HESX-1 gene (HESX-1) may cause autosomal-dominant IGHD, with penetrance that has been shown to be variable in both humans and mice. Subjects and Methods: We have sequenced the whole GH-1 in the index cases of 30 families with autosomal-dominant IGHD. In all the families other possible causes of GH deficiency and other pituitary hormones deficits were excluded. We here describe the clinical, biochemical and radiological picture of the families without GH-1 mutations. In these families, we also sequenced the HESX-1. Results: The index cases of the five families with autosomal-dominant IGHD had normal GH-1, including the intronic sequences. They had no HESX-1 mutations. Conclusion: This study shows that GH-1 mutations are absent in 5/30 (16.6%) of the families with autosomal-dominant IGHD and raises the possibility that mutations in other gene(s) may be involved in IGHD with this mode of transmission.
Association between Glycogen Synthase Kinase-3β Genetic Polymorphism and Late-Onset Alzheimer’s Disease
Authors: Mateo Ignacio , Infante Jon , Llorca Javier , Rodríguez Eloy , Berciano José , Combarros Onofre
Published: January 2006

Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer’s disease (AD) brains. Glycogen synthase kinase-3β (GSK-3β) phosphorylates tau protein, and increased GSK-3β expression has been associated with neurofibrillary tangles. Saitohin (STH) is a recently identified protein that shares tissue expression pattern with tau, and previous evidence in the Spanish population indicated that a polymorphism at codon 7 (Q7R) of the STH gene was associated with late-onset AD. Since both GSK-3β and STH are related to tau, we examined the association between a polymorphism in the promoter region (–50) of the GSK-3β gene and AD, either through an independent effect or through interaction with the STH (Q7R) polymorphism, in a well-defined group of 333 sporadic AD patients and 307 control subjects from Spain. The current study reveals that GSK-3β (–50) TT genotype is associated with an increased risk (OR 1.99, p = 0.003) for late-onset (after the age of 72 years) AD. Our results indicate that both the GSK-3β (–50) and STH (Q7R) polymorphisms increase the risk of late-onset (subjects >72 years) AD, although they appear to be independent and thus not to interact synergistically.
Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization
Authors: Varma Manu , Deatrick K. , Dewyer Nicholas , Lynch Erin , Moore Andrea , Dubay Derek , Sukheepod Pasu , Pearce Charles , Upchurch Gilbert , Kunkel Steven , Franz Michael , Wakefield Thomas , Henke Peter
Published: January 2006

Early deep venous thrombosis (DVT) resolution is associated with neutrophil (PMN) influx. This study examined the role of PMNs in thrombus neovascularization and vein wall injury after DVT. A rat model of DVT by inferior vena cava (IVC) ligation was performed with control serum or rabbit anti-rat PMN serum administered perioperatively with sacrifice at 2 and 7 days. At 2 days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and 1.4-fold higher femoral venous pressures by water manometry (P = .008) but no difference in thrombus neovascularization was observed. By7 days, DVT sizes were similar, but vein wall injury persisted in the neutropenic rats with a 2.0-fold increase in vein wall stiffness by microtensiometry (P< .05), as well asa 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors were significantly increased in neutropenic IVC at7 days (all P< .05).Vein wall and intrathrombus uPA by Western immunoblotting, and intrathrombus MMP-9 gelatinase activity were significantly less in neutropenic rats than controls (P < .001). Conversely, MMP-2 was significantly elevated in neutropenic IVC at 2 days after DVT. However, neutropenia induced 24 hours after DVT formation resulted in no significant increase in vein wall stiffness or collagen levels at 7 days, despite 1.4-fold larger thrombi (P < .05). These data suggest a critical early role for PMN in post DVT vein wall remodeling.
A role for immunoglobulin G in donor-specific Streptococcus sanguis-induced platelet aggregation
Authors: Zhu Raymond , Pesun Robert , Pampolina Caroline , Jackson Elke , Bowden George , Zelinski Teresa , McNicol Archibald
Published: January 2006

There is increasing evidence fora relationship between bacterial infections and several cardiovascular disorders. Although the precise mechanism(s) underlying this association is unknown, the direct activation of platelets by bacteria is one possibility. Individual strains of S. sanguis activate platelets in a non-uniform, donor-dependent manner. In the current study, platelet aggregation profiles were obtained for fourteen donors in response to four strains of S. sanguis (2017–78, 133–79, SK112, SK108a) and one of S. gordonii (SK8). The platelets from all donors responded to strains 2017–78 and 133–79,whereas strains SK112, SK8 and SK108a caused aggregation in one, five and twelve donors, respectively. Immunoglobulin G (IgG) binding to strains 2017–78, 133–79 and SK108a were significantly greater than to strains SK112 and SK8. Absorption of IgG by strain 2017–78 caused significant decreases in IgG binding, and platelet aggregation in response, to all strains. Single-strand conformational polymorphisms were observed in the FcγRIIA gene from four donors. Sequencing revealed two known and two novel point mutations, none of which correlated with the aggregation profile. Thus, platelet activation to the various strains depends ona common IgG and, while in most cases the level of IgG binding to S. sanguis determines platelet responsiveness, neither the levels of IgG nor FcγRIIA polymorphisms can fully account for donor variability.
No added value of the methionine loading test in assessment for venous thrombosis and cardiovascular disease risk
Authors: Keijzer Miranda , Verhoef Petra , Borm George , Blom Henk , den Heijer Martin
Published: January 2006

Homocysteine isa risk factor for cardiovascular disease and venous thrombosis. Clinical guidelines differ in their recommendation whether or not to measure homocysteine after methionine loading. In this study, we investigated the added value of the methionine loading test next to fasting homocysteine levels for identifying subjects at risk for venous thrombosis or cardiovascular disease, using Receiver Operating Characteristic (ROC) curves.The analysis was performed in 185 patients with recurrent venous thrombosis, 130 patients with cardiovascular disease and 601 controls.The discriminatory power of the fasting homocysteine measurement alone for identifying subjects at risk of venous thrombosis expressed as the area under the ROC curve (AUC) was 0.61 (95%CI 0.56-0.66). Using both a fasting homocysteine measurement and a methionine loading test together yielded a similar AUC of 0.65 (95%CI 0.60-0.69), indicating no added value of methionine loading next to fasting homocysteine measurement in identifying subjects at risk for thrombosis. Similar results where found for cardiovascular disease, with anAUC of 0.62 (95%CI 0.57-0.67) for the fasting homocysteine measurement alone and an AUC of 0.62 (95%CI 0.57-0.67) for the combination of both the fasting and the postload homocysteine measurement. The methionine loading test has no added value next to measuring fasting homocysteine levels for identifying subjects at risk for venous thrombosis or cardiovascular disease and for that reason should not be used in clinical practice.
Relation between ADAMTS13 activity and ADAMTS13 antigen levels in healthy donors and patients with thrombotic microangiopathies (TMA)
Authors: Hovinga Johanna A. , Konetschny Christian , Herzog Andrea , Koller Letizia , Weber Alfred , Remuzzi Giuseppe , Dockal Michael , Plaimauer Barbara , Rieger Manfred , Ferrari Silvia , Scheiflinger Friedrich
Published: January 2006

We have established a new, enzyme-linked immunosorbent assay (ELISA) for the detection of ADAMTS13 antigen using purified polyclonal rabbit anti-human ADAMTS13 IgG. Normal plasma ADAMTS13 antigen levels span a concentration of 740 –1420ng/ml (median 1080ng/ml) resulting in an ADAMTS13 activity to antigen ratio of 0.48 to 1.68 U/µg. In a cohort of HUS patients, ADAMTS13 antigen was in the normal range, whereas in hereditary TTP patients antigen levels were low to undetectable, in concordance with severe deficient ADAMTS13 activity. Plasma of acquired TTP patients was found to contain free as well as autoantibody-bound ADAMTS13. We also present evidence for circulating anti-ADAMTS13 antibody/ADAMTS13 antigen immune complexes not only in acutely ill or actively treated patients but also in patients who have already achieved clinical remission. This new developed ADAMTS13 antigen ELISA assay allows rapid determination of ADAMTS13 antigen levels in human plasma but is of limited predictive value for the diagnosis or treatment of acquired TTP due to the detection of ADAMTS13 in antibody complexes.
Tolerance to factor VIII in a transgenic mouse expressing human factor VIII cDNA carrying an Arg593 to Cys substitution
Authors: Hausl Christina , Zuurveld Marleen , Ahmad Rafi , Hollestelle Martine , Reitsma Pieter , Fijnvandraat Karin , van Lier Rene , Schwarz Hans , Mertens Koen , Reipert Birgit , Bril Wendy , van Helden Pauline , Voorberg Jan
Published: January 2006

Inhibitory antibodies develop in approximately 25% of patients with severe hemophilia A following treatment with factor VIII. In E-16KO or E-17KO mice, in which the factor VIII gene has been inactivated by insertion of a neo cassette, inhibitors develop following administration of factor VIII. Here, we describe the generation of transgenic mice expressing human factor VIII-R593C (huFVIII-R593C). Human factor VIII-R593C cDNA under control of a mouse albumin enhancer/promoter was injected into fertilized oocytes. Analysis of transgenic mice revealed that human factor VIII-R593C was expressed in the liver. Transgenic mice were crossed with factor VIII-deficient mice (E-16KO mice). In plasma of E-16KO mice antibodies were detected after five serial intravenous injections of factor VIII, while plasma of huFVIII-R593C/E-16KO mice did not contain detectable levels of antibodies. No antibody secreting cells were observed in either spleen or bone marrow of huFVIII-R593C/E-16KO mice. Also, factor VIII-specific memory B cells were not observed in the spleen of huFVIII-R593C/E-16KO mice. Analysis of T cell responses revealed that splenocytes derived of E-16KO mice secreted IL-10 and IFN-γ following restimulation with factor VIII in vitro. In contrast, no factor VIII-specific T cell responses were observed in huFVIII-R593C/E-16KO mice. These results indicate that huFVIII-R593C/E-16KO mice are tolerant to intravenously administered factor VIII. It is anticipated that this model may prove useful for studying immune responses in the context of factor VIII gene therapy.
Live birth following the first mutation specific pre-implantation genetic diagnosis for haemophilia A
Authors: Tuddenham Edward , Turner Cathy , Lavender Ben , Lavery Stuart , Michaelides Katerina
Published: January 2006

Haemophilia A is an X-linked, recessive, inherited bleeding disorder which affects 1 in 5000 males born worldwide. It is caused by mutations in the FactorVIII (F8) gene on chromosome Xq28. We describe for the first time two mutation specific, single cell protocols for pre-implantation genetic diagnosis (PGD) of haemophilia A that enable the selection of both male and female unaffected embryos. This approach offers an alternative to sexing, frequently used for X-linked disorders, that results in the discarding of all male embryos including the 50% that would have been normal. Two families witha history of severe haemophilia A requested carrier diagnosis and subsequently proceeded to PGD. The mutation in family1 isa single nucleotide substitution c. 5953C>T, R1966X in exon 18 and in family 2, c. 5122C>T, R1689C in exon 14 of the F8 gene. Amplification efficiency was compared between distilled water and SDS/proteinase K cell lysis (98.0%, 96/98 and 80%, 112/140 respectively) using 238 single lymphocytes. Blastomeres from spare IVF cleavage-stage embryos donated for research showed amplification efficiencies of 83.3% (45/54) for the R1966X and 92.9% (13/14) for the R1689C mutations. The rate of allele dropout (ADO) on heterozygous lymphocytes was 1.1% (1/93) for R1966X and 5.94% (6/101) for R1689C mutations. A single PGD treatment cycle for family1 resulted in two embryos for transfer but these failed to implant. However, with family 2, two embryos were transferred to the uterus on day 4 resulting in a successful singleton pregnancy and subsequent live birth of a normal non-carrier female.
Protein S levels modulate the activated protein C resistance phenotype induced by elevated prothrombin levels
Authors: Brugge Jeroen , Tans Guido , Rosing Jan , Castoldi Elisabetta
Published: January 2006

Elevated plasma prothrombin levels, due to the prothrombin 20210 G/A mutation or to acquired causes, area risk factor for venous thrombosis,partly because of prothrombin-mediated inhibition of the protein C anticoagulant pathway and consequent activated proteinC (APC) resistance. We determined the effect of plasma prothrombin concentration on the APC resistance phenotype and evaluated the role of protein S levels asa modulating variable. The effect of prothrombin and protein S levels on APC resistance was investigated in reconstituted plasma systems and in a population of healthy individuals using both the aPTT-based and the thrombin generation-based APC resistance tests. In reconstituted plasma, APC resistance increased at increasing prothrombin concentration in both assays. Enhanced APC resistance was caused by the effect of prothrombin on the clotting time in the absence of APC in the aPTT-based test, and on thrombin formation in the presence of APC in the thrombin generation-based test. In plasma from healthy individuals prothrombin levels were highly correlated to protein S levels. Since prothrombin and proteinS had opposite effects on the APC resistance phenotype, the prothrombin/protein S ratio was a better predictor of APC resistance than the levels of either protein alone. Prothrombin titrations in plasmas containing different amounts of proteinS confirmed that proteinS levels modulate the ability of prothrombin to induce APC resistance. These findings suggest that carriers of the prothrombin 20210 G/A mutation, who have a high prothrombin/protein S ratio, may experience a higher thrombosis risk than non-carriers with comparable prothrombin levels.
Anticoagulant and anti-platelet effects are maintained following coadministration of otamixaban, a direct factor Xa inhibitor, and acetylsalicylic acid
Authors: Hinder Markus , Frick Annke , Rosenburg Ronald , Hesse Galina , Ozoux Marie-Laure , Laux Volker , Scholtz Herman , Gebauer Alexander , Paccaly Anne
Published: January 2006

The pharmacokinetics, pharmacodynamics and safety of the direct factor Xa inhibitor, otamixaban, with and without concomitant acetylsalicylic acid (ASA) were investigated in healthy volunteers. The study was a double-blind, placebo-controlled 3-way crossover study. Sixty-eight male volunteers in total were randomised to otamixaban, ASA, or otamixaban with ASA. ASA (300 mg once a day) was started2 days before and continued on the day of the otamixaban 6-hour IV infusion (0.3 and 0.5 mg/kg). Pharmacokinetic and pharmacodynamic parameters (coagulation markers, platelet function tests and skin bleeding time) were determined. Drug interaction was assessed by the ratios of geometric means and 90 confidence intervals (90% CI)of the parameter estimates.

Pharmacokinetic parameters of otamixaban remain ed unchanged with ASA. Ratios of geometric means (90% CI) were for Ceoi 96.54 (91.21–102.19) and 95. 04 (90. 10–100. 24) and for AUC 98. 0 (93. 92–102. 25) and 95. 90 (92. 61–99. 31), for 0. 3 and 0. 5 mg/kg, respectively. No drug interaction was observed between otamixaban andASA on the coagulation and platelet function parameters. Neither otamixaban nor ASA had an effect on skin bleeding time; their co-administration led toa slight prolongation of skin bleeding time above the normal range without any clinically relevant bleeding. This study demonstrated that the desired effects of otamixaban and ASA, namely anticoagulation and platelet inhibition, respectively, are maintained during co-administration of both drugs.
Direct thrombin inhibitors built on the azaphenylalanine scaffold provoke degranulation of mast cells
Authors: Štempelj Mateja , Cerne Manica , Zega Anamarija , Obreza Aleš , Oblak Marko , Drevenšek Gorazd , Budihna Metka , Stanovnik Lovro , Urleb Uroš , Peternel Luka
Published: January 2006

The main structural feature of direct thrombin inhibitor LK-732 responsible for the appropriate interaction at the thrombin active site is a strong basic group. A possibility that a strong basic group of LK-732 might contribute to the mast cell degranulation effect and consequent reduction of tracheal air flow (TAF) and fall of mean arterial blood pressure (MAP) in rats was investigated in the present study. At doses up to5 mg/kg (i. v.), LK-732 did not cause significant changes of TAF and MAP. At 7 mg/kg (i. v.),a sudden reduction of TAF and a fall of MAP was observed within 5 min after LK-732 administration (75% mortality, p=0. 007). A less basic direct thrombin inhibitor LK-658 (21 mg/ kg, i. v.) did not significantly disturb TAF and MAP. A reduction of TAF and a fall of MAP caused by LK-732 (7 mg/kg, i. v.) was almost completely abolished in rats with degranulated mast cells (0% mortality, p=0. 008). LK-732 concentration-dependently degranulated rat peritoneal mast cells in vitro (pEC50=1. 92±0. 05 µM). A structure-activity relationship (SAR) study revealed that the terminal basic groups attached to the aromatic ring are responsible for the mast cell degranulation effect. A good correlation was observed between mast cell degranulation and pKb of analogues of LK-732 (R2=0. 49), but not between mast cell degranulation and thrombin Ki (R2=0. 23). LK-732-induced reduction of TAF, the fall of MAP and high mortality originate from LK732-induced mast cell degranulation. As judged by the SAR study, this effect could be overcome by reducing the basicity of LK-732.
Ethical Dilemmas Faced by Correctional Psychologists in Canada
Authors: Haag Andrew M.
Published: January 2006

There are numerous ethical issues that correctional psychologists in Canada face on a regular basis. This article analyzes the following ethical issues as they relate to the adult correctional context in Canada: (a) who is the client, (b) confidentiality, (c) protection of psychological records, (d) informed consent, (e) assessment, (f) corroboration, (g) refusal of services, (h) nondiscrimination, (i) competence, (j) knowledge of legal structure, (k) accuracy and honesty, (l) misuses of psychological information, and (m) multiple relationships. This article is organized around three of the four principles of the Canadian Psychological Association's ethics guide.
On the public use of practical reason
Authors: Maclure Jocelyn
Published: January 2006

A number of phenomena have lent a new complexity to the long-standing challenge of constructing a legitimate and stable political order. I contend that both legitimacy and integration under contemporary conditions ultimately hinge upon a form of public practical reasoning that departs considerably from the ones proposed by John Rawls, Jürgen Habermas and several deliberative democrats. I argue that the generalizability test that constitutes the cornerstone of most contemporary neo-Kantian theories of public reason should be abandoned as a rule of public argumentation and be replaced by a norm of civic responsiveness towards minority claims. I not only suggest that a wider variety of reasons, motives and genres of speech needs to be admitted within the purview of public reason, but more fundamentally that generalizability cannot cogently be seen as anything more (or less) than a civic virtue. The underlying point of this article is that neo-Kantian theories of public reason work with a problematic conception of practical reason. I conclude by providing reasons, against some radical and agonistic democrats, why the language of public reasoning needs to be retained and renovated.
Ernesto Laclau and the logic of ‘the political’
Authors: Norris Andrew
Published: January 2006

Ernesto Laclau's theory of antagonism and political identity has been widely celebrated as one of the most promising attempts to apply the lessons of ‘poststructuralism’ to political theory. This essay argues, however, that this initial promise is not fulfilled. Laclau's attempt to define and analyse ‘the political’ as such operates at such an abstract level that Laclau is forced to make sweeping claims about the nature of politics and identity that he simply cannot support; and his analysis of the decision that he claims defines politics is an unrealistic one that celebrates violence, and could have the wide appeal it has had only in a political culture that understood freedom as the absence of all constraint, rather than the achievement of autonomy.
Ambivalence to Technology in Jeunet’s Le Fabuleux Destin d’Amélie Poulain
Authors: Moore Rick Clifton
Published: January 2006

Although at one level Jean-Pierre Jeunet’s Le Fabuleux Destin d’Amélie Poulain is a sweet, attractive film about a young Parisian doing good deeds, it also offers a compelling analysis of the role of technology in our modern lives. The film paints a world where machines and a mechanistic worldview are appealing because humans have a desire to control their destinies but threatening because humans value freedom. The work of French social theorist Jacques Ellul is especially useful in analyzing these facets of the film as technology and freedom were consistent themes in his various books on the modern milieu.
The Implications of High-Rate Nanomanufacturing on Society and Personal Privacy
Authors: Rodrigues Ruben
Published: January 2006

The growing field of nanotechnology has received considerable attention as of late. The U.S. National Nanotechnology Initiative has committed billions of dollars toward research on the nanoscale, and proponents of nanotechnology claim that its benefits will range from curing cancer to ending poverty. This article takes a look at the possible benefits and problems associated with the development of high-rate nanomanufacturing technologies, specifically in regards to privacy. Nanosensors, small enough to avoid detection by the naked eye and that are produced cheaply enough, could be used as tracking or listening devices. There may be useful applications of such technologies for some defense, intelligence, and medical and industrial purposes; however, widespread availability and abuse of such sensors is a cause for concern. The adequacy of existing legislation concerning technology and privacy is reviewed and possible courses of action for placating any negative effects of nanomanufacturing on personal privacy considered.
Conversationalization and media empowerment in Greek television discussion programs
Authors: Patrona Marianna
Published: January 2006

This article explores the conversational practices of the hosts of Greek television discussion programs vis-à-vis experts. The aim is to discover, first, the extent to which media talk in Greece echoes the attested conversationalization of western media discourse, and, second, the discourse manifestations of this tendency in the Greek television media. It is shown that the discourse of hosts does indeed display an affinity to informal conversation. More specifically, far from sustaining a formally neutral stance, the presenters engage in overt alignment-building in support of experts, or, conversely, issue direct challenges toward them. In this framework, politicians are positioned as defendants in a courtroom hearing. It is argued that the hosts' strategies of personal involvement illustrate the celebration of personality by the media, and supply evidence of the empowerment of media actors and media institutions. Furthermore, the discursive practices of moderators help constitute the mediated political sphere in contemporary Greece.
Restorative justice, Navajo Peacemaking and domestic violence
Authors: Coker Donna
Published: January 2006

I argue that RJ processes may be beneficial for some women who experience domestic violence, but only if those processes meet five criteria: prioritize victim safety over batterer rehabilitation; offer material as well as social supports for victims; work as part of a coordinated community response; engage normative judgments that oppose gendered domination as well as violence; and do not make forgiveness a goal of the process. I review my earlier study of Navajo Peacemaking in light of these criteria. I also explore the significant differences between Peacemaking and other processes that are said to be derived from Indigenous justice models, noting in particular that the process is completely controlled by the Navajo Nation.
Doing difference and accountability in restorative justice conferences
Authors: Cook Kimberly J.
Published: January 2006

This article analyses social dynamics in restorative justice conferences employing two distinct meanings of accountability: one embodied in performing gendered (and other) social relations, and the second, in performing remorse. Engaging feminist theory of ‘doing gender’ and structured action, offenders’ accounts of their behaviour, gendered participation of parents and community representatives are analysed. Specifically examined are three ideals of restorative justice: empowerment, remorse and reintegration, and bridging barriers between participants. The data analysed are from extensive field notes collected during six months of research into restorative justice in Australia and as a practitioner in Maine. Analyses reveal that achieving these ideals is more elusive than anticipated. Rather, accountability dynamics around gender, race and social class reinforce social privileges and disadvantage.
Lay Theories and Intergroup Relations
Authors: Levy Sheri R. , Chiu Chi-yue , Hong Ying-yi
Published: January 2006

Lay theory research on intergroup relations has rapidly grown over the past two decades. Drawing on articles in this Special Issue, we showcase the latest developments. First, we define lay theories, addressing the extent of overlap with scientific theories and differences among lay theories in terms of type of representation, level of articulation, frequency of activation and use, range of applicability, and degree of universality. Second, we describe advances in the understanding of the functions of lay theories. Third, we review the far-reaching implications of lay theories for group and intergroup processes. Fourth, we discuss the movement toward comparing and contrasting related lay theories. Taken together, these articles suggest the study of lay theories provides a fuller understanding of intergroup relations.
Lay Theories of Essentialism
Authors: Demoulin Stéphanie , Leyens Jacques-Philippe , Yzerbyt Vincent
Published: January 2006

This article investigates the essentialist perception of social categories and differentiates it from two closely related concepts, namely entitativity and natural kind-ness. We argue that lay perceptions of social categories vary along three dimensions: natural kind-ness, entitativity, and essentialism. Depending on whether membership in social categories is forced or chosen, people develop different theories and associate different types of characteristics. Perceived control upon membership in the categories influences perceptions of entitativity and natural kind-ness but has no direct impact on the attribution of essentialism to the groups.
The Roles of Entitativity and Essentiality in Judgments of Collective Responsibility
Authors: Denson Thomas F. , Lickel Brian , Curtis Mathew , Stenstrom Douglas M. , Ames Daniel R.
Published: January 2006

Two studies investigated the roles of entitativity and essentiality in judgments of collective responsibility. Analyses focused on four group types (i.e. intimacy groups, task groups, social categories, and loose associations). Repeated measures analyses revealed that intimacy groups and task groups were rated highest in entitativity while intimacy groups and social categories were rated highest in essentiality. Correlational analyses revealed that entitativity played a more central role in judgments of collective responsibility for all four group types. However, tests of interaction effects revealed that essentiality moderated the effect of entitativity on blame judgments. Implications of the role of collective responsibility in intergroup relations are discussed.