bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Merozoite Surface Protein Markers byPlasmodium falciparum-Infected Erythrocytes in Peripheral Blood and Tissues of Children with Fatal Malaria
Authors: Dobaño Carlota , Rogerson Stephen J. , Taylor Terrie E. , McBride Jana S. , Molyneux Malcolm E. 
Published: November 2006

ABSTRACTSequestration ofPlasmodium falciparum-infected erythrocytes is a pathological feature of fatal cerebral malaria.P. falciparumis genetically diverse among, and often within, patients. Preferential sequestration of certain genotypes might be important in pathogenesis. We compared circulating parasites with parasites sequestered in the brain, spleen, liver, and lung in the same Malawian children with fatal malaria, classifying serotypes using antibodies to merozoite surface proteins 1 and 2 and immunofluorescence in order to differentiate parasites and to quantify the proportions of each serotype. We found (i) similar distributions of various serotypes in different tissues and (ii) concordance between parasite serotypes in peripheral blood and parasite serotypes in tissues. No serotypes predominated in the brain in cerebral malaria, and parasites belonging to a single serotype did not cluster within individual vessels or within single tissues. These findings do not support the hypothesis that cerebral malaria is caused by cerebral sequestration of certain virulent types.
A Tracer Dose of Technetium-99m–Labeled Liposomes Can Estimate the Effect of Hyperthermia on Intratumoral Doxil Extravasation
Authors: Kleiter Miriam M. , Yu Daohai , Mohammadian Lenore A. , Niehaus Nelsen , Spasojevic Ivan , Sanders Linda , Viglianti Benjamin L. , Yarmolenko Pavel S. , Hauck Marlene , Petry Neil A. , Wong Terence Z. , Dewhirst Mark W. , Thrall Donald E. 
Published: November 2006

Abstract
Purpose: A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)–labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation.
Experimental Design: Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured.
Results: Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil.
Conclusions: The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.
A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model
Authors: Ohno Hiroaki , Kubo Kazuo , Murooka Hideko , Kobayashi Yoshiko , Nishitoba Tsuyoshi , Shibuya Masabumi , Yoneda Toshiyuki , Isoe Toshiyuki 
Published: November 2006

Abstract
In bone metastatic lesions, osteoclasts play a key role in the development of osteolysis. Previous studies have shown that macrophage colony-stimulating factor (M-CSF) is important for the differentiation of osteoclasts. In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclast-dependent osteolysis in bone metastatic lesions. We developed small molecule inhibitors against ligand-dependent phosphorylation of c-Fms and examined the effects of these compounds on osteolytic bone destruction in a bone metastasis model. We discovered a novel quinoline-urea derivative, Ki20227 (N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N′-[1-(1,3-thiazole-2-yl)ethyl]urea), which is a c-Fms tyrosine kinase inhibitor. The IC50s of Ki20227 to inhibit c-Fms, vascular endothelial growth factor receptor-2 (KDR), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor β were found to be 2, 12, 451, and 217 nmol/L, respectively. Ki20227 did not inhibit other kinases tested, such as fms-like tyrosine kinase-3, epidermal growth factor receptor, or c-Src (c-src proto-oncogene product). Ki20227 was also found to inhibit the M-CSF-dependent growth of M-NFS-60 cells but not the M-CSF-independent growth of A375 human melanoma cells in vitro. Furthermore, in an osteoclast-like cell formation assay using mouse bone marrow cells, Ki20227 inhibited the development of tartrate-resistant acid phosphatase–positive osteoclast-like cells in a dose-dependent manner. In in vivo studies, oral administration of Ki20227 suppressed osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. Moreover, Ki20227 decreased the number of tartrate-resistant acid phosphatase–positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats. These findings suggest that Ki20227 inhibits osteolytic bone destruction through the suppression of M-CSF-induced osteoclast accumulation in vivo. Therefore, Ki20227 may be a useful therapeutic agent for osteolytic disease associated with bone metastasis and other bone diseases. [Mol Cancer Ther 2006;5(11):2634–43]
Tumor localization and antitumor efficacy of novel sapphyrin compounds
Authors: Naumovski Louie , Sirisawad Mint , Lecane Philip , Chen Jun , Ramos Jason , Wang Zhong , Cortez Cecilia , Magda Darren , Thiemann Patti , Boswell Garry , Miles Dale , Cho Dong Gyu , Sessler Jonathan L. , Miller Richard 
Published: November 2006

Abstract
Sapphyrins are pentapyrrolic metal-free expanded porphyrins with potential medical use as anticancer agents. The novel sapphyrin derivative, PCI-2050, functionalized with 2-[2-(2-methoxyethoxy)ethoxy]ethoxy groups to enhance solubility and a modified bipyrrole moiety was found to be more potent in inducing apoptosis than the previously described sapphyrin PCI-2000. Because some sapphyrins may localize to tumors, we took advantage of the intrinsic fluorescence of these compounds to develop a flow cytometry–based assay to track sapphyrin biodistribution in tumor-bearing mice. Ex vivo analysis of sapphyrin-injected animals revealed that PCI-2050 preferentially localized to tumor, whereas PCI-2000 distributed into normal tissues rather than tumor. PCI-2050 uptake in xenograft tumor cells and resultant tumor cell cytotoxicity was dose dependent. To investigate structure–activity relationships, we focused on PCI-2050 and three derivatives that differ by their alkyl substituents on the bipyrrole moiety: PCI-2051, PCI-2052, and PCI-2053. Treatment of Ramos cells in culture or treatment of Ramos xenograft-bearing animals with each of the sapphyrins followed by ex vivo growth of tumor cells revealed the same pattern of cytotoxicity: PCI-2050 &gt; PCI-2052 &gt; PCI-2051 &gt; PCI-2053. Thus, subtle changes in the alkyl substituents on the bipyrrole moiety result in significant changes in antitumor activity. PCI-2050 displayed significant antitumor efficacy in both Ramos and RKO xenograft models without hematologic, hepatic, or renal abnormalities as assessed by complete blood counts and serum chemistries. On the basis of these findings, it is concluded that the sapphyrin PCI-2050 warrants further evaluation as a potential anticancer agent due to its intrinsic proapoptotic activity and tumor localization ability. [Mol Cancer Ther 2006;5(11):2798–805]
The poor's curse: Exodus xxii 20-26 and curse literature in the ancient world
Authors: Ben-Dov Jonathan 
Published: November 2006

AbstractIn the passage Exod. xxii 20-26 the poor man cries to God after he had been mal-treated by a powerful creditor. In response God acts as an avenger against that evil individual. The article first clarifies the background to such violent acts by proprietors in Ancient Near Eastern Laws, and the response to it in the laws of Deuteronomy xxiv. The curse and revenge are then explained in the light of parallel practices from ancient Greek literature, mainly from the Oddesey. Curse practices meant to restore justice are explored on the basis of Greek binding spells and of the corpus of Greek literary curses. The image of the Mesopotamian god "ama" as an avenging god is analyzed according to the famous Babylonian "ama" hymn and to that god's epitheta. Finally, examples of Hebrew curse literature are highlighted in the Book of Job and in Psalm cix.
The "effected object" in contractual legal language: the semantics of "If you purchase a Hebrew slave" (Exod. xxi 2)
Authors: Levinson Bernard M. 
Published: November 2006

AbstractThis article investigates the semantics of the protasis of the manumission law of the Covenant Code (Exod. xxi 2a). Despite the proposal by John Van Seters that the slave there purchased must "already" have been a slave, such a restriction of meaning goes beyond the evidence. Critical for understanding the semantic issue is the overlooked distinction between two types of verbal object: "affected" and "effected" objects. Moreover, verbs of creation and appointment are frequently ditransitive. Such verbs may also leave the affected object implicit while specifying only the effected object. This construction emphasizes the change in status undergone by the grammatical patient, as in the case of the manumission law. Attention to the contractual language of biblical law permits, in turn, a more adequate concept of the grammatical concept of effected object.
Animal Liberationist Responses to Non-Anthropogenic Animal Suffering
Authors: Thornhill Richard , Morris Michael 
Published: November 2006

AbstractAnimal liberationists generally pay little attention to the suffering of animals in the wild, and it is arguable that this is a significant proportion of the total amount of animal suffering. We examine a range of different responses of animal liberationists to the issue of non-anthropogenic suffering, but find none of them entirely satisfactory. Responses that lead logically to the conclusion that anthropogenic suffering should be eliminated can apply equally logically to the suffering of animals in the wild. On the other hand, the solution of micro-managing habitats to prevent suffering is counter-intuitive, and on closer examination eliminates the intrinsic value of animals' lives. On balance, the approach that we favour is acceptance of the intrinsic value of individual animal lives, extending this from either individual human lives (as accepted predominantly by theists), or from biodiversity, species and ecosystems (as currently accepted by ecocentric philosophies). We also suggest that the combination of animal liberation and environmentalism only really makes sense in the context of a belief in the redeemable qualities of nature, as expressed in quasi-Hindu terms or in terms of some Biblical animal liberationist worldviews.
Dwelling in Dialogues: Being-at-home in Relation to Clutter, Nature, and People
Authors: Klenk Nicole , Kozak Robert , Bull Gary 
Published: November 2006

Abstract"Home" may be understood as an intangible concept separate from its material manifestation—the tangible place where one dwells, the house. However, this is not necessarily the way people experience the two concepts of "home" and "house". In daily life, both the experience of the tangible and the intangible dimensions of "home" may be inextricably linked. To explore how lived religion and spirituality relate to these dimensions, we engaged practicing Buddhists and Christians in dialogue about the role of their home in the practice of their faiths. Three major topics emerged from the interview process: clutter, nature, and people. The overlapping but distinct perspectives on these topics that the two groups of participants offer illustrate common dialectics that characterize the experience of "home".
Churches as a Stock of Social Capital for Promoting Social Development in Western Cape Communities
Authors: Swart Ignatius 
Published: November 2006

AbstractThe aim of the article is to present a perspective on the manner and extent to which churches may be considered as an important stock of social capital for promoting social development outcomes in selected communities in the Western Cape, South Africa. Taking the recently presented policy outline on social capital formation in this province as the contextual framework for analysis and reflection, the results of recently executed demographic and socio-empirical research are utilised in particular to advance a perspective on churches. It is argued in conclusion that churches and other faith-based organisations in the researched communities have an important strategic significance for a social capital formation agenda, despite their apparent lack of progressive social praxis. Their comparative advantage over other institutions, the considerable levels of trust invested in them and the manner in which they inspire activities of voluntary outreach, caring and social service are highlighted as special features of the churches.
The railroadmen's social condition and the evolution of the American railroad system
Authors: Carré Stéphane 
Published: November 2006

AbstractWhile Europe is commiting itself to operating its railway network more freely, the United States have been living since the beginning under competition in that branch. This situation brought about the development of hard working conditions for its employees at first. Yet, since the companies were compelled to operate on a high security level as well as to imperiously allow anybody to have access to this service, they were quickly subdued to stringent control restricting the way they were working and granting social advantages far beyond the rights of the employment law to their railroadmen. This set of rules was implemented by a specific federal organisation, the "Interstate Commerce Organisation", as well as by a special law, the "Railway Labor Act", building a tight frame when industrial disputes break out in that branch. The "Staggers Act", if loosening these rules, didn't aim at questioning them.
Truth and secret: the protection of privacy in ancient German, French and English law
Authors: Balthasar Stephan 
Published: November 2006

AbstractComparing the legal development in France, Germany and England from 1500–1800, this article analyses the protection of those interests which are covered today by the law of privacy. Continental law, influenced by the Roman actio iniuriarum, protected personal secrets, and it also restrained, to a certain extent, the divulgation of embarrassing truths. The English law of defamation however, afforded no comparable protection, the proof of truth ("justification") being a perfect defence against any claim for damages under the head of defamation. The conclusion that the civil law has a long tradition of preserving sensitive information against unwanted publicity is underlined by the fact that the ancient ideas of protecting secrets and restricting publication of the truth helped 19th century lawyers in France and in Germany to approach the modern concept of privacy ("vie privée", "Privatleben").
Hematopathological Concepts and Controversies in the Diagnosis and Classification of Myelodysplastic Syndromes
Authors: Vardiman James W. 
Published: November 2006

Abstract
Although the diagnosis and classification of most cases of the myelodysplastic syndromes (MDS) is usually accomplished without difficulty, a minority of cases may pose diagnostic problems. In many cases the diagnostic dilemma can be solved by adhering to basic guidelines recommended for evaluation of patients suspected of having MDS, and in particular to the quality of the blood and bone marrow specimens submitted for morphologic, immunophenotypic and genetic studies. In other cases, such as patients who have hypocellular MDS or MDS with fibrosis, the criteria for making a diagnosis may be difficult if not impossible to apply, and in still others the diagnostic uncertainty is because the minimal criteria necessary to establish the diagnosis of MDS are not always clearly stated. In this review, some of these diagnostic problems are addressed and some general guidelines for resolving them are suggested. In addition, data are presented that illustrate that the WHO classification offers a valuable tool in the diagnosis and classification of MDS.
Clinical Issues in the Management of Patients with Myelodysplasia
Authors: Schiffer Charles A. 
Published: November 2006

AbstractThe management of patients with myelodysplasia (MDS) can be quite complex and varies according to both the clinical manifestations in individual patients as well as complicating medical conditions. Allogeneic stem cell transplantation is the only curative treatment, but because of the older age of the patient population must be applied selectively, particularly in those with lower risk MDS as well as in patients whose clinical course is more frankly “preleukemic.” Issues pertinent to the use of 5-azacytidine, decitabine and lenalidomide in patients with both higher and lower International Prognostic Staging System (IPSS) stage disease are discussed.
Current and Investigational Therapies for Patients with CLL
Authors: Wierda William G. 
Published: November 2006

AbstractClinical and laboratory investigations are driving the rapid change in treatments for patients with chronic lymphocytic leukemia (CLL). Randomized trials have demonstrated superior activity for fludarabine combined with cyclophosphamide versus single-agent fludarabine or chlorambucil as initial treatment. Chemoimmunotherapy holds promise for further improvement and is being tested in randomized trials. New combinations and agents are being identified and tested. Eliminating minimal residual disease is a therapeutic endpoint that may prove to prolong survival and is also under investigation in prospective clinical trials. Work continues toward improving survival and potentially curing patients of this disease.
Think of HIT
Authors: Warkentin Theodore E. 
Published: November 2006

AbstractHeparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common—isolated thrombocytopenia, venous thromboembolism, acute limb ischemia—to less common but specific presentations—necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 × 109/L, and ranges from 15 to 150 × 109/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin (“delayed-onset HIT”) is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to “think of HIT.” Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, ?fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.
Thrombotic Thrombocytopenic Purpura: A Moving Target
Authors: Sadler J. Evan 
Published: November 2006

Abstract
Almost 80 years after Eli Moschcowitz published the first description of the disease, most patients with idiopathic thrombotic thrombocytopenic purpura (TTP) were found to have acquired autoantibody inhibitors of the ADAMTS13 metalloprotease. Plasma ADAMTS13 normally cleaves von Willebrand factor within nascent platelet-rich thrombi, and ADAMTS13 deficiency allows unchecked thrombus growth to cause microangiopathic hemolysis, thrombocytopenia, and tissue infarction. At present, ADAMTS13 deficiency with a high-titer inhibitor level appears to be associated with an increased risk of early death and subsequent relapse. Thus, acquired ADAMTS13 deficiency identifies a specific mechanism of TTP and is a potential biomarker of disease activity or risk. At present, two major clinical questions in the field may be summarized as follows. First, by emphasizing TTP caused by ADAMTS13 deficiency, are we in danger of neglecting other causes that should be treated with plasma exchange? Second, should we treat asymptomatic patients who have severe ADAMTS13 deficiency to prevent future disease, and if so, how?
Bleeding Disorders in Premenopausal Women: (Another) Public Health Crisis for Hematology?
Authors: James Andra H. , Ragni Margaret V. , Picozzi Vincent J. 
Published: November 2006

Abstract
Premenopausal women with bleeding disorders represent a major public health problem. Estimates suggest up to 20% of women with menorrhagia have an underlying bleeding disorder (corresponding to a prevalence of 1.5–4 million American women). Von Willebrand disease (VWD) is the most common bleeding disorder among women with menorrhagia, affecting up to 20% of such patients. Besides menorrhagia, important consequences of bleeding disorders in premenopausal women include iron deficiency anemia, miscarriage, postpartum bleeding, uterine bleeding and hysterectomy. These patients face many obstacles in achieving optimum care. Recognition is difficult as women may consider their symptoms “normal” and come to attention only after serious bleeding events. Symptoms of VWD may also overlap with benign conditions, primary providers may not suspect the diagnosis, and convenient hematologic input may be unavailable. Diagnosis is difficult as there is no single definitive test for VWD, and test results are variable, often being affected by extragenic factors, including stress, contraceptives, hormones, and pregnancy. Hemostatic treatment is limited by DDAVP tachyphylaxis, the lack of recombinant VWD concentrates, and the ineffectiveness of hormonal therapy, leading to unnecessary procedures and early hysterectomy. Finally, significant controversy exists regarding classification of type 1 VWD as a disease: given the overlap in symptoms and laboratory assays within the normal population, evaluation for those with VWD might be seen as identification of potential bleeding risk rather than detection of a disease. This symposium seeks to explore these issues in greater detail from the combined perspectives of the obstetrician-gynecologist and the hematologist to promote a better public health approach to this problem.