bluuebunny/crossref_metadata_2025 huggingface dataset:
JP-8 jet fuel exposure results in immediate immunotoxicity, which is cumulative over time
Authors: Harris David T , Sakiestewa Debbie , Titone Dominic , Young R Scott , Witten Mark
Published: June 2003

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. In the present study, the immediate effects of JP-8 exposure on the immune system were analyzed. Exposure of mice once to a single 1000 mg/m3 concentration of JP-8 for one hour resulted in significant immune organ weight loss and loss of viable immune cells from the spleen within two hours post-exposure. Although a similar exposure had no effect on thymus organ weight, it did result in significant losses of viable immune cells at one hour post-exposure. It was also observed that a loss of viable bone marrow cells could be seen at four hours post-exposure, with a return to baseline levels by 24 hours post-exposure. In terms of peripheral blood immune cells, a significant loss of viable immune cells was observed within one hour post-exposure, which became more pronounced with time. Further, it was observed that a single one-hour JP-8 exposure resulted in an immediate loss of immune function at one hour post-exposure that did not recover within 24 hours. An extension of the above experiments revealed that each additional one hour/day of exposure to 1000 mg/m3 of JP-8 promulgates the significant immunotoxicity described above. That is, spleenic organ weights, as well as viable cell numbers, continued to decline with additional days of short-term exposure. Thymic organ weights were significantly reduced at three to four days of one-hour exposures, with a continuing loss of viable cell numbers. Significantly, functional immune responses continued to deteriorate with each additional day of JP-8 exposure. Thus, low concentration JP-8 jet fuel exposures have significant effects on the immune system, these effects occur rapidly and these effects are cumulative over time.
The need for preventive drugs and vaccines in global cancer control: a challenge for public health and for industry
Authors: Vainio Harri
Published: June 2003

Ten million new cancer patients are diagnosed worldwide each year. There will be a dramatic increase over the next 20 years in the number of people contracting cancer, especially in the developing, poorer part of the world. Many types of cancer vary in incidence and mortality by more than an order of magnitude between different populations, and every type is rare in some part of the world, suggesting that cancers are in principle preventable. Many specific causes of cancer are known, from factors related to lifestyle, diet, infections and occupations. The remarkable advances in molecular understanding of the carcinogenesis process over the past 25 years have transformed the approaches in cancer control. About 15% of cancers worldwide are caused by known infectious agents. Human papillomavirus vaccines, which are already being tested, may, in the long run, be able to prevent almost all cervical cancers. New promising disciplines in prevention, such as chemoprevention, have emerged. Chemoprevention has been successfully achieved in numerous animal experiments, and has been validated in several clinical trials. But more effective and safer chemopreventive agents and vaccines are needed. Rising prices of medicines and vaccines are putting them beyond the reach of many people, even in rich countries. Future enhanced efforts on an international basis are needed to guarantee access to these lifesaving drugs and vaccines. Putting prevention high on the agenda requires political courage and a long-term perspective.
The Tyrosine Phosphatase Shp-2 Mediates Intracellular Signaling Initiated by Ret Mutants
Authors: D’Alessio A. , Califano D. , Incoronato M. , Santelli G. , Florio T. , Schettini G. , Carlomagno M. S. , Cerchia L. , de Franciscis V.
Published: June 2003

The Src homology 2-containing tyrosine phosphatase, Shp-2, is a crucial enzyme that mediates intracellular signaling and is implicated in cell proliferation and differentiation. Here we investigated the involvement of the Shp-2 tyrosine phosphatase in determining the downstream signaling pathways initiated by the Ret oncogene, carrying either the cysteine 634 to tyrosine or the methionine 918 to threonine substitutions. These mutations convert the receptor tyrosine kinase, Ret, into a dominant transforming protein and induce constitutive activation of its intrinsic tyrosine kinase activity leading to congenital and sporadic cancers in neuroendocrine organs. Using the PC12, rat pheochromocytoma cell line, as model system, we show that Shp-2 mediates immediate-early gene expression if induced by either of the mutant alleles. Furthermore, we show that Shp-2 activity is required for RetM918T-induced Akt activation. The results indicate that Shp-2 is a downstream mediator of the mutated receptors RetC634Y and RetM918T, thus suggesting that it may act as a limiting factor in Ret-associated endocrine tumors, in the neoplastic syndromes multiple endocrine neoplasia types 2A and 2B.
Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4
Authors: Costin Gertrude-E. , Valencia Julio C. , Vieira Wilfred D. , Lamoreux M. Lynn , Hearing Vincent J.
Published: June 2003

Oculocutaneous albinism (OCA) type 4 is a newly identified human autosomal recessive hypopigmentary disorder that disrupts pigmentation in the skin, hair and eyes. Three other forms of OCA have been previously characterized, each resulting from the aberrant processing and/or sorting of tyrosinase, the enzyme critical to pigment production in mammals. The disruption of tyrosinase trafficking occurs at the level of the endoplasmic reticulum (ER) in OCA1 and OCA3, but at the post-Golgi level in OCA2. The gene responsible for OCA4 is the human homologue of the mouse underwhite (uw) gene, which encodes the membrane-associated transporter protein (MATP). To characterize OCA4, we investigated the processing and sorting of melanogenic proteins in primary melanocytes derived from uw/uw mice and from wild-type mice. OCA4 melanocytes were found to be constantly secreted into the medium dark vesicles that contain tyrosinase and two other melanogenic enzymes, Tyrp1(tyrosinase-related protein 1) and Dct (DOPAchrome tautomerase); this secretory process is not seen in wild-type melanocytes. Although tyrosinase was synthesized at comparable rates in wild-type and in uw-mutant melanocytes,tyrosinase activity in uw-mutant melanocytes was only about 20% of that found in wild-type melanocytes, and was enriched only about threefold in melanosomes compared with the ninefold enrichment in wild-type melanocytes. OCA4 melanocytes showed a marked difference from wild-type melanocytes in that tyrosinase was abnormally secreted from the cells, a process similar to that seen in OCA2 melanocytes, which results from a mutation of the pink-eyed dilution (P) gene. The P protein and MATP have 12 transmembrane regions and are predicted to function as transporters. Ultrastructural analysis shows that the vesicles secreted from OCA4 melanocytes are mostly early stage melanosomes. Taken together, our results show that in OCA4 melanocytes, tyrosinase processing and intracellular trafficking to the melanosome is disrupted and the enzyme is abnormally secreted from the cells in immature melanosomes, which disrupts the normal maturation process of those organelles. This mechanism explains the hypopigmentary phenotype of these cells and provides new insights into the involvement of transporters in the normal physiology of melanocytes.
Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1- and EGF-dependent signalling pathways
Authors: Haase Ingo , Evans Richard , Pofahl Ruth , Watt Fiona M.
Published: June 2003

Adult epidermal keratinocytes migrate by crawling, a process that requires protrusion of the plasma membrane at the front of the cell and contraction of the cell body at the rear. We have found that epidermal growth factor (EGF)and insulin-like growth factor 1 (IGF-1) influence keratinocyte shape differently. Whereas IGF-1 stimulates membrane protrusion and facilitates cell spreading, EGF induces contraction of keratinocytes. The effects of each growth factor on keratinocyte shape are mediated by distinct signal transduction pathways: EGF stimulates the activity of the classical mitogen-activated protein kinase pathway and IGF-1 stimulates phosphatidylinositol-3-kinase. Activation of these kinases is both necessary and sufficient to induce cell shape changes upon growth factor treatment. In addition, IGF-1-stimulated keratinocyte spreading depends on the activation of Rho family proteins. In vitro assays of wound re-epithelialization show that both growth factors stimulate migration of keratinocytes, and the activity of the respective signalling pathways is required for this re-epithelialization process. When added simultaneously, IGF-1 and EGF have additive effects on wound epithelialization. Our results show that IGF-1 and EGF can influence different components of the keratinocyte migration machinery that determines the speed of wound epithelialization.
Lipid- and protein-mediated multimerization of PSD-95: implications for receptor clustering and assembly of synaptic protein networks
Authors: Christopherson Karen S. , Sweeney Neal T. , Craven Sarah E. , Kang Rujun , El-Husseini Alaa El-Din , Bredt David S.
Published: June 2003

Postsynaptic density protein 95 (PSD-95/SAP-90) is a palmitoylated membrane-associated guanylate kinase that oligomerizes and clusters ion channels and associated signaling machinery at excitatory synapses in brain. However, the mechanism for PSD-95 oligomerization and its relationship to ion channel clustering remain uncertain. Here, we find that multimerization of PSD-95 is determined by only its first 13 amino acids, which also have a remarkable capacity to oligomerize heterologous proteins. Multimerization does not involve a covalent linkage but rather palmitoylation of two cysteine residues in the 13 amino acid motif. This lipid-mediated oligomerization is a specific property of the PSD-95 motif, because it is not observed with other palmitoylated domains. Clustering K+ channel Kv1.4 requires interaction of palmitoylated PSD-95 with tetrameric K+ channel subunits but, surprisingly, does not require multimerization of PSD-95. Finally, disrupting palmitoylation with 2-bromopalmitate disperses PSD-95/K+-channel clusters. These data suggest new models for K+ channel clustering by PSD-95 – a reversible process regulated by protein palmitoylation.
Disruption of lipid order by short-chain ceramides correlates with inhibition of phospholipase D and downstream signaling by FcϵRI
Authors: Gidwani Arun , Brown H. Alex , Holowka David , Baird Barbara
Published: June 2003

Specialized plasma membrane domains known as lipid rafts participate in signal transduction and other cellular processes, and their liquid-ordered properties appear to be important for their function. We investigated the possibility of using amphiphiles to disrupt lipid rafts and thereby inhibit IgE-FcϵRI signaling. We find that short-chain ceramides –C2-ceramide and C6-ceramide – decrease plasma membrane lipid order and reduce the extent of fluorescence resonance energy transfer between lipid-raft-associated molecules on intact cells; by contrast,biologically inactive C2-dihydroceramide does neither. Structural perturbations by these ceramides parallel their inhibitory effects on antigen-stimulated Ca2+ mobilization in RBL mast cells in the presence and absence of extracellular Ca2+. Similar inhibition of Ca2+ mobilization is caused by n-butanol, which prevents phosphatidic acid production by phospholipase D, but not by t-butanol, which does not prevent phosphatidic acid production. These results and previously reported effects of short-chain ceramides on phospholipase D activity prompted us to compare the effects of C2-ceramide,C2-dihydroceramide and C16-ceramide on phospholipase D1 and phospholipase D2 activities in vitro. We find that the effects of these ceramides on phospholipase D1 activity strongly correlate with their effects on antigen-stimulated Ca2+ mobilization and with their disruption of lipid order. Our results indicate that phospholipase D activity is upstream of antigen-stimulated Ca2+ mobilization in these cells, and they demonstrate that ceramides can serve as useful probes for investigating roles of plasma membrane structure and phospholipase D activity in cellular signaling.
Regulation of eosinophil membrane depolarization during NADPH oxidase activation
Authors: Bankers-Fulbright Jennifer L. , Gleich Gerald J. , Kephart Gail M. , Kita Hirohito , O'Grady Scott M.
Published: June 2003

Protein kinase C (PKC) activation in human eosinophils increases NADPH oxidase activity, which is associated with plasma membrane depolarization. In this study, membrane potential measurements of eosinophils stimulated with phorbol ester (phorbol 12-myristate 13-acetate; PMA) were made using a cell-permeable oxonol membrane potential indicator, diBAC4(3). Within 10 minutes after PMA stimulation, eosinophils depolarized from–32.9±5.7 mV to +17.3±1.8 mV. The time courses of depolarization and proton channel activation were virtually identical. Blocking the proton conductance with 250 μM ZnCl2(+43.0±4.2 mV) or increasing the proton channel activation threshold by reducing the extracellular pH to 6.5 (+44.4±1.4 mV) increased depolarization compared with PMA alone. Additionally, the protein kinase C(PKC) δ-selective blocker, rottlerin, inhibited PMA-stimulated depolarization, indicating that PKCδ was involved in regulating depolarization associated with eosinophil NADPH oxidase activity. Thus, the membrane depolarization that is associated with NADPH oxidase activation in eosinophils is sufficient to produce marked proton channel activation under physiological conditions.
Receptor activation regulates cortical, but not vesicular localization of NDP kinase
Authors: Gallagher Betty C. , Parrott Kimberly A. , Szabo Gabor , de S. Otero Angela
Published: June 2003

We used immunofluorescence techniques to determine the localization of nucleoside diphosphate (NDP) kinase in NIH-3T3 fibroblasts. We found that cytoplasmic NDP kinase can be separated into two populations according to subcellular localization and response to extracellular stimuli. Specifically,within minutes of stimulation of resting fibroblasts with serum, growth factors or bombesin, a portion of NDP kinase becomes associated with membrane ruffles and lamellipodia. Another pool of NDP kinase accumulates independently of stimulation around intracellular vesicles. Transfection of cells with activated Rac mimics, whereas expression of dominant negative Rac inhibits,the effects of extracellular stimulation on the translocation of NDP kinase to the cell cortex. Neither Rac mutant affects the vesicle-associated pool. Association of NDP kinase with vesicles depends on microtubule integrity and is disrupted by nocodazole. In cell-free assays NDP kinase binds tightly to membrane vesicles associated with taxol-stabilized microtubules. Binding of NDP kinase to this fraction is reduced by ATP and abolished by GTP, as well as guanine nucleotides that are NDP kinase substrates. Thus, the localization of the two NDP kinase pools identified here is regulated independently by distinct cellular components: the appearance of cortical NDP kinase is a consequence of Rac activation, whereas vesicular NDP kinase is responsive to microtubule dynamics and nucleotides, in particular GTP. These results suggest that in fibroblasts NDP kinase participates in Rac-related cortical events and in GTP-dependent processes linked to intracellular vesicle trafficking.
Sprouty: how does the branch manager work?
Authors: Guy Graeme R. , Wong Esther S. M. , Yusoff Permeen , Chandramouli Sumana , Lo Ting Ling , Lim Jormay , Fong Chee Wai
Published: June 2003

Since the discovery of the prototypical Sprouty (Spry) protein in Drosophila, there has been an effort to determine how these novel modulators of the Ras/MAP-kinase pathway function. A clue to their mechanism of action comes from the several highly conserved sequences within all the currently known Spry isoforms: an ∼110-residue cysteine-rich sequence in the C-terminal half that directs Spry proteins to a concentration of signaling proteins at the plasma membrane; a small motif surrounding a tyrosine residue(Y55 in human Spry2) that is responsible for interaction with other proteins. In cultured mammalian cells, hSpry2 inhibits epidermal growth factor receptor(EGFR) endocytosis and subsequently sustains the activation of MAP kinase but negatively regulates the same pathway following stimulation of fibroblast growth factor receptors (FGFRs). Current evidence indicates that Cbl is a key protein that interacts directly with Spry2 following activation of receptor tyrosine kinases (RTKs). It appears to be the ability of Cbl to interact as an E3 ubiquitin ligase on specific target proteins and as a docking protein in other contexts that dictates the differential effects Spry2 has on the Ras/MAP-kinase pathway following EGFR and FGFR activation.
Proliferating cell nuclear antigen (PCNA): a dancer with many partners
Authors: Maga Giovanni , Hübscher Ulrich
Published: June 2003

Proliferating cell nuclear antigen (PCNA) was originally characterised as a DNA sliding clamp for replicative DNA polymerases and as an essential component of the eukaryotic chromosomal DNA replisome. Subsequent studies,however, have revealed its striking ability to interact with multiple partners, which are involved in several metabolic pathways, including Okazaki fragment processing, DNA repair, translesion DNA synthesis, DNA methylation,chromatin remodeling and cell cycle regulation. PCNA in mammalian cells thus appears to play a key role in controlling several reactions through the coordination and organisation of different partners. Two major questions have emerged: how do these proteins access PCNA in a coordinated manner, and how does PCNA temporally and spatially organise their functions? Structural and biochemical studies are starting to provide a first glimpse of how both tasks can be achieved.
HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O2 levels
Authors: Masson Norma , Ratcliffe Peter J.
Published: June 2003

Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that plays a crucial role in mediating cellular responses to oxygen. Oxygen availability influences multiple steps in HIF activation and recent studies have indicated that at least two steps in this process are governed by a novel mode of signal transduction involving enzymatic hydroxylation of specific amino acid residues in HIF-α subunits by a series of 2-oxoglutarate(2-OG)-dependent oxygenases. These enzymes are non-haem iron enzymes that use dioxygen in the hydroxylation reaction and therefore provide a direct link between the availability of molecular oxygen and regulation of HIF. Prolyl hydroxylation regulates proteolytic destruction of HIF-α by the von Hippel-Lindau ubiquitin ligase complex, whereas HIF-α asparaginyl hydroxylation regulates recruitment of transcriptional coactivators. The involvement of at least two distinct types of 2-OG-dependent oxygenase in oxygen-regulated transcription suggests that these enzymes may be well suited to a role in cellular oxygen sensing.
Mesostructured Alumina Nanocomposites Synthesized via Reverse Microemulsion Route
Authors: You Zhixiong , Balint Ioan , Aika Ken-ichi
Published: June 2003

Mesostructured alumina nanocomposites, with 10 nm pores after 500 °C calcination, have been synthesized by reverse-microemulsion route.
Spontaneous Dispersion of PdO onto Acid Sites of Zeolites Studied by in situ DXAFS
Authors: Okumura Kazu , Kusakabe Tetsuji , Yokota Shigeru , Kato Kazuo , Tanida Hajime , Uruga Tomoya , Niwa Miki
Published: June 2003

The generation of highly dispersed PdO over zeolite supports was studied using in situ energy-dispersive XAFS (DXAFS) technique. From the comparison with the Na-ZSM-5, it was found that the oxidation as well as the spontaneous dispersion of Pd was promoted through the interaction between PdO and acid sites of H-form zeolites.
The discourse of globalisation and the logic of no alternative: rendering the contingent necessary in the political economy of New Labour
Authors: Watson Matthew , Hay Colin
Published: June 2003

English

Although convincingly discredited academically, a crude ‘business school’ globalisation thesis of a single world market, with its attendant political ‘logic of no alternative’, continues to dominate the discourse of globalisation adopted by the British Labour Party. Here, we identify three separate, albeit reinforcing, articulations of the policy ‘necessities’ associated with global economic change. Labour’s leaders are shown to have utilised a flexible synthesis of potentially contradictory ideas in constructing their chosen discourse of globalisation to guide the conduct of British economic policy following the Party’s election victory in 1997. We conclude that Labour appealed to the image of globalisation as a non-negotiable external economic constraint in order to render contingent policy choices ‘necessary’ in the interests of electoral rejuvenation.
Privileged or exploited council tenants? The discursive change in Conservative housing policy from 1972 to 1980
Authors: Jacobs Keith , Kemeny Jim , Manzi Tony
Published: June 2003

English

The process of social construction in which competing and sometimes contradictory definitions contend with one another plays a decisive part in policy making. Justifications for policy intervention often require a narrative identifying villains or victims to delineate creatively a ‘social problem’ that needs to be addressed by appropriate measures. This article shows how contrasting political and media representations of council tenants in the 1960s and 1970s provided the emotive justifications for two distinct policies: ‘Fair Rents’ and the ‘Right to Buy’. The article concludes that more attention should be paid to the way that the successful mobilisation of bias legitimises policy interventions.
In search of social capital
Authors: Johnston Gordon , Percy-Smith Janie
Published: June 2003

English

Social capital is increasingly regarded by politicians, policy makers and theoreticians as an antidote to a range of social ills and its absence as a cause of those same ills. Originating in Bourdieu and popularised by Putnam, much is claimed for social capital. However, there is little agreement on what social capital is, where it comes from, how it can be measured and, if it is a ‘good thing’, how we can get more of it. This article reviews the main schools of thought relating to social capital, summarises what is being claimed for it and then sketches out a research agenda to address the unresolved issues surrounding this attractive but elusive concept.
Reterritorialising health: inclusive partnerships, joined-up governance and common accountability platforms in Third Way New Zealand
Authors: Craig David
Published: June 2003

English

Recent health policy changes in New Zealand have included substantive reterritorialisation of governance and provision, as well as the emergence of well-being initiatives targeting specific places. At the same time, a range of place- and population-related community provider organisations has emerged as partners to government and each other. Documenting these changes in the wider contexts of social determinants of health, third way ‘social inclusion’, urban geographies of poverty, place positioning and decentralisation, this article discusses emerging difficulties and challenges in achieving policy coherence, spatial equity and consistent local collaboration. It concludes by discussing the potential role and scope of place-based ‘common accountability platforms’.
New forms of local accountability: coming to terms with ‘many hands’?
Authors: Sullivan Helen
Published: June 2003

English

The transformation of many western liberal democracies in the late 20th century has had important implications for the practice of public accountability, compounding the problem of ‘many hands’. This article considers developments in academic debate and discusses how traditional modes of vertical accountability can be augmented by new horizontal mechanisms. New Labour’s approach to local ‘modernisation’ in England is examined, including, but going beyond, local government, to consider new institutions that seek to ‘join up’ local action. The article concludes that to manage the problem of ‘many hands’ requires specific intervention from local government in its community leadership role.
Controlling the PFI process in schools: a case study of the Pimlico project
Authors: Edwards Pamela , Shaoul Jean
Published: June 2003

English

This article explores how the control procedures designed to ensure value for money in the context of the Private Finance Initiative (PFI), operate in the context of schools, using the case of the Pimlico redevelopment project. The evidence casts doubt on the strict regulatory control of this project, particularly in terms of meeting the identified needs of the school, ensuring value for money and affordability. The article considers the suitability of the PFI methodology and the process to appraise PFI schools projects, where the interests and different responsibilities of the local education authority and school governors may conflict.
Welfare state development in the context of European integration and economic convergence: situating Ireland within the European Union context
Authors: O’Connor Julia S.
Published: June 2003

English

Convergence towards the European Community average on key economic dimensions was the dominant objective of Ireland’s entry into the Community in 1973 and is now central to the admission aspirations of the applicant countries. This article outlines key aspects of Ireland’s economic convergence and the associated policy choices. It examines whether its welfare state is converging towards the European Union average in expenditure and selected distributional outcomes and discusses its welfare regime characterisation. The simultaneous processes of economic convergence and maintenance of traditional social policy patterns are identified, as are differences between the economic development and distributional roles of the state.
Rheological properties of LDPE processed by conventional processing machines
Authors: Yamaguchi Masayuki , Todd David B. , Gogos Costas G.
Published: June 2003

The impact of applied processing history and the postprocessing annealing on the rheological properties of low‐density polyethylene (LDPE) have been studied employing various kinds of conventional processing machines. Processing by a corotating twin‐screw extruder (Co‐TSE) and an internal batch mixer depressed the drawdown force, one of the elastic properties of a melt, to a great extent, even though molecular weight and the polydispersity did not change. On the other hand, the sample processed by a two‐roll mill exhibited the drawdown force as high as the original pellets, which is owing to the intermittent stress history instead of the relentless one in the Co‐TSE and the internal batch mixer. Furthermore, the effect of screw configuration in the Co‐TSE has also been investigated. It was found that the processing by conveying screws depressed the drawdown force and melt fracture more than that by kneading blocks as long as the torque and the residence time are the same. The large, abrupt, and frequent change in flow direction in the Co‐TSE with kneading blocks prohibits the molecular orientation, which leads to disentanglement associated with long‐chain branches. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 179–187, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10047
Prediction of cooling time in injection molding by means of a simplified semianalytical equation
Authors: Zarkadas D. M. , Xanthos M.
Published: June 2003

A simplified semianalytical equation, used successfully in food freezing/chilling time prediction, is proposed as a potential simple alternative for cooling time prediction in injection molding of polymer parts, amorphous or semicrystalline. This equation is based on a convective boundary condition for the mold‐part interface and requires information on the thermal contact resistance (TCR) or thermal contact conductance (TCC) at this interface, as well as information on the initial and final product temperatures, the mold surface temperature, and the thermal properties of the part. Eighty‐five data points for four polymers, Polystyrene (PS), Polycarbonate (PC), Polypropylene (PP), and Polyethylene (PE) were generated with C‐MOLD™, a commercial injection molding design software, and the performance of the proposed equation was tested. The % mean error and its standard deviation (SD) in cooling time prediction were, respectively, −11.61 and 2.27 for PS, −6.04 and 2.13 for PC, −7.27 and 6.55 for PP, and −8.88 and 2.93 for PE. It was also shown that the accuracy of the proposed equation is not affected significantly by the exact knowledge of the TCC, provided that the latter is not smaller than 1000–2000 W m−2 K−1. Since in this comparison all necessary temperatures were obtained from C‐MOLD™, methods of using the proposed equation independently were tested. The use of the inlet melt temperature as the initial product temperature increased the % mean error by mostly 1.5% while its SD remained practically the same. By incorporating a literature based heat balance method in the proposed equation, it was possible to use it as a stand‐alone predictor of polymer cooling time. The % mean error and its SD calculated this way were, respectively, −9.44 and 0.97 for PS, −9.44 and 0.83 for PC, −14.22 and 5 for PP, and −20.12 and 1.38 for PE. The proposed equation, at least in a preliminary stage, can be used successfully to predict the cooling time of the selected semicrystalline or amorphous polymers with the accuracy being higher for amorphous polymers. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 188–208, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10048
Binary blends of EVA and metallocene‐catalyzed ethylene‐α‐olefin copolymers and their film properties
Authors: Kontopoulou Marianna , Huang Leo C. , Lee Jennifer A.
Published: June 2003

Blends of Ethylene‐Vinyl Acetate (EVA) copolymer with a metallocene (single‐site type) catalyzed elastomeric ethylene‐α‐olefin copolymer have been investigated, with a focus on film applications. These blends were found to be immiscible in the melt and solid state, but mechanically compatible. EVA rich blends had a coarser morphology and showed more pronounced shear thinning and elastic behavior, suggesting better processability during the extrusion film blowing process. Ethylene‐α‐olefin copolymer rich blends displayed finer morphologies, better tensile, heat seal, and optical properties and less extrudate swell. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 209–217, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10049
Improved polyurethane dispersion stability via continuous process
Authors: Keyvani Majid
Published: June 2003

This paper presents a continuous process for producing waterborne polyurethane dispersion (PUD) with improved shelf life stability. The work also demonstrates that when a typical batch operation fails to produce stable PUD products because of low emulsifier content and/or absence of solvent, the continuous process offers reasonable colloidal stability performance. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 218–224, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10050
Secondary gas penetrations in ribs during full‐shot gas‐assisted injection molding
Authors: Yang Sen‐Yeu , Lin Chui‐Te , Chang Jer‐Haur
Published: June 2003

Although gas‐assisted injection molding (GAIM) eliminates sink marks and prevents warpage, many problems are encountered during gas‐assisted filling owing to gas–melt flow interactions. Large voids created by gas penetration during gas‐assisted filling result in degraded rigidity. To avoid gas‐assisted filling, the shot weight is increased to 100%. Gas is injected after the cavity is completely filled. The so‐called “full‐shot gas‐assisted injection molding” process is investigated in this paper. The effects of the processing conditions and rib geometry on the behavior of gas penetration are systematically investigated. High melt temperature and a short gas injection delay time are found to increase the length of gas penetration during full‐shot GAIM. Wide ribs and ribs with fillets cause the gas penetration length to decrease. Although the mechanisms of gas penetration for short‐shot and full‐shot GAIMs are not identical, the resulting penetration patterns of the gas void shape are similar.© 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 225–237, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10051
Experimental determination of gelation and swelling parameters using time‐resolved fluorescence technique
Authors: Pekcan Ö. , Kaya D. , Erdoğan M.
Published: June 2003

A fast transient fluorescence (FTRF) technique was used to study the sol–gel transition during gelation of methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDM). Pyrene (Py) was used as a fluorescence probe for the in situ polymerization experiments. Swelling of this cylindrical poly(methyl methacrylate) (PMMA) gel in chloroform was monitored using FTRF technique. Fluorescence lifetimes of Py from its decay traces were measured and used to monitor both the gelation and swelling processes. Stern–Volmer kinetics were employed to determine the quenching rate constant before the onset of gelation. MMA consumption rate was measured during gelation process using the Stern–Volmer model. A Li–Tanaka equation was introduced to determine the cooperative diffusion coefficient Dc, which was found to be around 10−5 cm2 s−1 during the swelling of PMMA gel in chloroform. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 238–245, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10052
Thermoresponsive poly(N‐isopropylacrylamide‐co‐N‐vinylimidazole) hydrogels by redox polymerization
Authors: Işik Belma
Published: June 2003

Thermoresponsive hydrogels in the form of rods were prepared from N‐isopropylacrylamide (NIPAM) and N‐vinylimidazole (NIV) by a redox copolymerization method. Poly(NIPAM‐co‐NVI) hydrogels with different thermoresponsive properties were obtained by changing the initial NIPAM/NVI mole ratio and total monomer concentrations. Equilibrium swelling ratio, dynamic swelling ratio, and dynamic deswelling ratio were evaluated for all hydrogels systems. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 246–251, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10053
Swelling behavior of poly(N‐vinyl‐2‐pyrrolidone) and poly(N‐vinyl‐2‐pyrrolidone)/K2S2O8 hydrogels in α‐lactose solutions
Authors: Can Hatice Kaplan , Kavlak Serap , Kırcı Betül , Güner Ali
Published: June 2003

Hydrogels with varying cross‐linking densities, and average molecular weights between two consecutive cross‐links, were prepared from the binary poly(N‐vinyl‐2‐pyrrolidone)/water and ternary poly(N‐vinyl‐2‐pyrrolidone)/water/K2S2O8 systems by irradiation with γ‐rays at ambient temperature. Both hydrogel systems were employed for diffusion and swelling experiments in 0.00278 M α‐lactose solution at room temperature. Diffusion of α‐lactose solution into hydrogels was found to be of the Fickian type. The percent swelling, equilibrium swelling, initial rate of swelling, swelling rate of constant, equilibrium water/α‐lactose content, and diffusion constant values were determined for PVP and PVP/K2S2O8 hydrogel systems in 0.00278 M α‐lactose solution. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 252–259, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10054
Primary B‐cell lymphoma and lymphoma‐like lesions of the uterine cervix
Authors: Au W.Y. , Chan B.C.P. , Chung L.P. , Choy C.
Published: June 2003

We present three patients with atypical lymphoid cells on cervical smear screening, with diffuse large‐cell B‐cell lymphoma diagnosed by morphology on cervical biopsy. One patient with extensive pelvic disease was treated with chemotherapy and radiotherapy and remained in remission 8 years later. Two patients with presumed stage 1E lesions showed spontaneous regression on repeat cervical biopsy, despite light chain restriction and clonal immunoglobulin gene rearrangement. They are without recurrent malignancy 1 and 5 years after their initial diagnosis. The presence of malignant looking lymphoid cells on cervical smear should be investigated by repeated colposcopic biopsies. The reason for the highly skewed atypical B‐cell lymphoproliferation in lymphoma‐like lesions of the cervix is unknown. With early stage, nonbulky cervical lymphoma in an otherwise healthy patient, a cone biopsy is advised. A number of these lesions may regress even when clonal populations are detected. Am. J. Hematol. 73:176–179, 2003. © 2003 Wiley‐Liss, Inc.
Pulmonary Balantidium coli infection in a leukemic patient
Authors: Anargyrou K. , Petrikkos G.L. , Suller M.T.E. , Skiada A. , Siakantaris M.P. , Osuntoyinbo R.T. , Pangalis G. , Vaiopoulos G.
Published: June 2003

A 59‐year‐old woman suffering from chronic lymphocytic leukemia developed pulmonary lesions; bronchoalveolar lavage was performed for possible systemic fungal infection. However, direct microscopic analysis revealed ciliated protozoa identified as Balantidium coli. B. coli is the only known pathogenic ciliate, and is usually associated with intestinal infection in areas associated with pig rearing. On very rare occasions the organisms may invade extra‐intestinal organs, in this case the lungs of an immunocompromised patient. This case is unusual as balantidiasis is rare in Europe, the patient had no obvious contact with pigs, and there was no history of diarrhea prior to pulmonary colonization. Metronidazole was rapidly administered, and the condition improved after 24–48 hr. Am. J. Hematol. 73:180–183, 2003. © 2003 Wiley‐Liss, Inc.
CD34 expression is associated with poor clinical outcome in patients with acute promyelocytic leukemia
Authors: Lee Je‐Jung , Cho Duck , Chung Ik‐Joo , Cho Sang‐Hee , Park Kyeong‐Soo , Park Moo‐Rim , Ryang Dong‐Wook , Kim Hyeoung‐Joon
Published: June 2003

This study investigated the clinical characteristics and prognostic relevance of CD34 expression in 47 patients with acute promyelocytic leukemia (APL), showing t(15;17) or PML/RARα. Ten (21.3%) of the APL patients were CD34+. CD34 expression was associated with hypogranular morphology (P = 0.002) and hyperleukocytosis (P = 0.015). However, there were no statistically significant differences in age, sex, hemoglobin level, platelet count, or percentage of blasts between the CD34+ and CD34− APL groups. Multiplex RT‐PCR analysis showed that the L‐form (BCR1) and S‐form (BCR3) were correlated with CD34− APL and CD34+ APL, respectively. Despite the lack of a difference in the complete remission rate, overall survival (OS) and disease‐free survival (DFS) were significantly lower in the CD34+ group than in the CD34− group (P = 0.012 and P = 0.0051, respectively). By multivariate analysis, the CD34+ group showed a significant independent variable in DFS compared with the CD34− group, but this was not demonstrated for OS. In conclusion, CD34 expression in APL is a unique clinical feature associated with leukocytosis and atypical morphology with hypogranular pattern and is associated with a poor clinical outcome. Am. J. Hematol. 73:149–153, 2003. © 2003 Wiley‐Liss, Inc.
Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia
Authors: Balta Gunay , Yuksek Nazmiye , Ozyurek Emel , Ertem Ulya , Hicsonmez Gonul , Altay Cigdem , Gurgey Aytemiz
Published: June 2003

The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S‐transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05–1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03–1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. Am. J. Hematol. 73:154–160, 2003. © 2003 Wiley‐Liss, Inc.
Pleural effusion of a second neoplasm in a patient with B‐CLL: Two immunological compartments
Authors: Atanackovic D. , Brettner S. , Hegewisch‐Becker S.
Published: June 2003

We report the case of a patient with a chronic lymphocytic leukemia (CLL) who later developed a metastasized large‐cell neuroendocrine carcinoma of the lung that was complicated by a malignant pleural effusion. In contrast to the peripheral blood where the malignant B‐CLL cells represented >99% of all lymphocytes, lymphocytes infiltrating the malignant effusion were mainly T cells. Nearly all of these T cells were CD4+. This stood in sharp contrast to the peripheral blood where the CD4+/CD8+ ratio remained balanced. A detailed analysis of the CD4+ T cells within the malignant effusion revealed that these cells uniformly expressed a CCR7+ CD62L+ “non‐effector” phenotype. When the monoclonal B cells within the malignant effusion were analyzed, we found that these cells, in contrast to the B‐CLL cells in the peripheral blood, were negative for CD23 and expressed much higher levels of the adhesion molecules L‐selectin (CD62L) and CD11a. A deficient expression of these adhesion molecules might have led to a “trapping” of the majority of B‐CLL cells in the peripheral blood. This phenomenon might have contributed to the development of two highly different immunological compartments in this patient with CLL and pleural effusion of a solid tumor. Am. J. Hematol. 73:184–189, 2003. © 2003 Wiley‐Liss, Inc.
Combined chemotherapy including high‐dose methotrexate in KSHV/HHV8‐associated primary effusion lymphoma
Authors: Boulanger Emmanuelle , Daniel Marie‐Thérèse , Agbalika Félix , Oksenhendler Eric
Published: June 2003

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8‐associated high‐grade non‐Hodgkin's lymphoma (NHL) of B‐cell origin, characterized by serous effusions in body cavities. Most patients are HIV‐infected homosexual men with severe immunosuppression and other KSHV/HHV8‐associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High‐dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS‐associated PEL were treated with a combined chemotherapy including high‐dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre‐existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD‐associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS‐associated PEL with combined chemotherapy containing high‐dose methotrexate. Am. J. Hematol. 73:143–148, 2003. © 2003 Wiley‐Liss, Inc.
Busulfan, cyclophosphamide, and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma
Authors: Cogle Christopher R. , Moreb Jan S. , Leather Helen L. , Finiewicz Katarzyna J. , Khan Shahab A. , Reddy Vijay S. , Wingard John R.
Published: June 2003

Autologous stem cell transplantation (ASCT) has enabled the use of high‐dose alkylating agents either as a single agent or in combination with other cytotoxic agents and/or total body irradiation (TBI) for the treatment of multiple myeloma. Despite improved complete remission rates, relapse and regimen‐related toxicities remain challenging. In an effort to increase event‐free survival and decrease the high incidence of regimen‐related toxicity, we have studied the use of etoposide in combination with reduced‐dose busulfan and cyclophosphamide as a conditioning regimen for ASCT in a group of 26 patients with advanced multiple myeloma. Median follow‐up for the group was 30 months. There was no early treatment‐related mortality. The main toxicity was mucositis. Otherwise, there was 1 case of reversible, clinically diagnosed hepatic veno‐occlusive disease. Post‐engraftment, 10 patients (38%) achieved CR, 15 (58%) patients achieved PR or SD, and 1 patient developed progressive disease (4%). Five patients in PR and 1 with progressive disease before transplant attained a CR post‐transplant. The median times for event‐free survival and overall survival after transplantation were 24 and 43 months, respectively. In conclusion, conditioning with busulfan, cyclophosphamide, and etoposide followed by ASCT is a safe regimen with comparable effectiveness to other previously used preparative regimens, thus providing another approach of non‐TBI containing high‐dose chemotherapy for patients with multiple myeloma. Am. J. Hematol. 73:169–175, 2003. © 2003 Wiley‐Liss, Inc.